Introduction
Anatomy and Physiology of bone
Bone Tissue Engineering
Recent studies related to bone tissue engineering
Commercialized products and ongoing clinical trials
Biomedical start-ups
Concluding remarks
Introduction
Anatomy and Physiology of bone
Bone Tissue Engineering
Recent studies related to bone tissue engineering
Commercialized products and ongoing clinical trials
Biomedical start-ups
Concluding remarks
Introduction
Anatomy and Physiology of bone
Bone Tissue Engineering
Recent studies related to bone tissue engineering
Commercialized products and ongoing clinical trials
Biomedical start-ups
Concluding remarks
Tissue engineering involves using cells, biomaterials, and growth factors to regenerate damaged tissues and organs. There are several strategies for tissue engineering, including injecting stem cells, using scaffolds to guide cell growth, and inducing cell differentiation. Ideal scaffolds are biocompatible, porous, and gradually degrade as new tissue forms. Common scaffold materials include natural polymers, ceramics, and synthetic polymers. Tissue-engineered dental tissues are being developed by harvesting patient cells and growing them on scaffolds or as cell sheets to regenerate the periodontal ligament.
This document provides an overview of the field of tissue engineering. It defines tissue engineering as an interdisciplinary field that applies engineering and life science principles toward the development of biological substitutes that restore or improve tissue function. The key goals of tissue engineering are to repair, replace, or regenerate tissues and whole organs. Current clinical treatments involve grafting methods like autografts, allografts, and xenografts, but these have limitations like immune rejection and donor scarcity. Tissue engineering aims to address these issues by using scaffolds, cells, and growth factors to regenerate tissues. Challenges in the field include properly mimicking the tissue microenvironment, scaling up production, and developing vascularization within engineered tissues.
Tissue engineering aims to augment, improve, treat or replace tissues using cells, biomaterials, and physiochemical factors. It requires appropriate cells, a scaffold for structure, and growth factors. Recent examples include artificial skin, muscle for meat production, implanted bladders, and cartilage for knee repair. Scaffolds must allow cell attachment, migration, and diffusion while providing mechanical support and inducing physiological changes in seeded cells. Bone contains osteoblasts that form bone and osteoclasts that resorb it. Its extracellular matrix includes hydroxyapatite and collagen fibers. Potential artificial bone materials include metals, ceramics, polymers, and coral hydroxyapatite. Osteoconduction provides a scaffold for bone formation, while osteo
Dr. Raghavendra Raju gave a presentation on tissue engineering. He began by defining key terms like tissue engineering, regenerative medicine, bionics, biomimetic materials, and stem cell therapy. The basic principles of tissue engineering involve using artificial or inert scaffold materials combined with living cells to grow desired tissues. Mesenchymal stem cells from bone marrow are commonly used due to their ability to differentiate into bone and cartilage cells. Applications in orthopedics include treating bone defects, fractures that won't heal, cartilage damage, and tendon/meniscus injuries. Future advances in fields like molecular biology and tissue engineering may help manage anatomical changes from disease.
Tissue engineering aims to regenerate tissues by combining cells, scaffolds, and signaling molecules. There are two main strategies - in vitro construction of tissues in the lab prior to implantation, and in vivo regeneration of tissues at the implantation site. Successful tissue engineering requires the right cells, scaffolding for cell attachment and growth, and signaling to guide tissue development. Stem cells are promising cell sources due to their ability to differentiate into many cell types.
bone and_cartilage_tissue_engineering by SumitDcrust
This document discusses tissue engineering of bone and cartilage. It defines tissue engineering as applying engineering and life science principles to develop biological substitutes that restore or improve tissue function. The key components of tissue engineering are cells, scaffolds, and bioreactors. Scaffolds provide structure for cell attachment and growth, while bioreactors provide cell signaling and mechanical stimulation. The document outlines current treatments for bone and cartilage defects and their limitations, as well as materials used in scaffolds and bioreactors. It discusses the need for and future of bone and cartilage tissue engineering.
Tissue engineering uses scaffolds, cells, and signaling molecules to regenerate tissues and organs. Scaffolds provide a structure for cell attachment, growth, and tissue formation. Natural polymers like collagen and hyaluronic acid, and synthetic polymers like poly-lactic-co-glycolic acid are commonly used as scaffold materials. Scaffolds can be fabricated using various methods including freeze drying, electrospinning, 3D printing, and textile technologies to produce scaffolds with desirable properties like porosity and pore size for tissue growth. Scaffolds seeded with stem cells or tissue-specific cells aim to repair and regenerate tissues for applications in skin, bone, cartilage, and other organs.
The document discusses tissue engineering approaches for the nervous system. It begins with an introduction to the anatomy and limited regenerative capacity of the central and peripheral nervous systems. For peripheral nerve injuries, the current gold standard treatment is autologous nerve grafts, but these have limitations. Alternative approaches discussed include the use of nerve guides containing matrices and scaffolds to bridge gaps and guide axon regeneration. Factors like scaffold composition and geometry, inclusion of cells and growth factors, and degradation properties can influence how well scaffolds support regeneration across critical gaps in nerves. The document reviews considerations for scaffold and matrix design and various strategies for incorporating growth-promoting components in peripheral nerve engineering.
Introduction
Artificial skin
Invention
Structure of human skin
Importance of skin
Key development
Biomaterials
Methods to produce artificial skin
Application
Problems
Future development
Conclusions
references
Tissue engineering involves growing tissues or organs by seeding cells onto biodegradable scaffolds. There are several key steps in the tissue engineering process: (1) cells are isolated from a patient and cultured, (2) the cells are seeded onto a scaffold to allow adhesion and growth, (3) the seeded scaffolds may be placed in a bioreactor to mimic the body's conditions and stimulate growth, (4) the engineered tissues are implanted into the patient. Bioreactors help distribute cells throughout the scaffold and provide mechanical and chemical cues to influence cell behavior.
Biomaterials were defined as “any substance, other than a drug, or a combination of substances, synthetic or natural in origin, which can be used for any period of time, as a whole or as a part of a system, which treats, augments or replaces any tissue, organ or function of the body”
Despite advances in organ transplantation, thousands still die each year waiting for donor organs. Tissue engineering aims to construct artificial organs and tissues in vitro by combining cells, biomaterials, and growth factors to replace diseased organs. Some key challenges include developing scaffolds that mimic the extracellular matrix, integrating multiple cell types, and applying mechanical and chemical signals to direct tissue development. While tissue engineering has shown promise for tissues like bone and skin, fully regenerating complex organs that do not naturally regenerate has yet to be achieved. Further research is still needed to meet clinical and patient expectations for safety, effectiveness and cost.
This document discusses the history and development of biomaterials. It begins by describing early biomaterials like gold, iron, brass and glass that were used by physicians with little consideration of material properties. The document then outlines major developments in biomaterials from the 1860s to the present day for applications like orthopedics, dental, cardiovascular and others. Key points covered include the regulatory framework for biomaterials and medical devices as well as current and future directions in the field.
This document summarizes tissue engineering approaches for engineering cardiovascular tissues. It discusses how cardiovascular disease is a leading cause of death and current treatment limitations. The main targets for tissue engineering are blood vessels, heart muscle, and heart valves. Commonly used biomaterials include polymeric scaffolds, hydrogels, and decellularized tissues. Appropriate cell types and biomolecules are also discussed. The challenges of engineering different cardiovascular tissues like blood vessels, heart valves, and heart muscle are briefly outlined.
Cartilage Repair using Stem cell & OrthobiologicsVaibhav Bagaria
Regenerating Cartilage is a challenge. What's new in this field of cartilage regeneration and the current status of the stem cell use in this field is described.
Introduction
Definition
History
Principle
Cell sources
What cells can be used?
Scaffolds
Biomaterials
Bioreactor
How tissue engineering is done?
How does tissue engineering differ from cloning?
Tissue engineering of specific structures
Application of tissue engineering
Limitations
Conclusion
References
Tissue engineering involves using scaffolds, cells, and biomolecules to create functional 3D tissues. It aims to develop biological substitutes to restore tissue function and repair damaged tissues, avoiding problems with organ transplants, mechanical devices, and surgery. A major goal is designing scaffolds that recreate the in vivo microenvironment through biophysical and biochemical signaling. Stem cells are a promising cell source for their ability to integrate into tissues and secrete growth factors. Signaling molecules can also be used to modulate cell behavior. Magnetic targeting of stem cells may help with the challenge of cell retention in tissue engineering applications like cardiac repair.
This document discusses biomaterials and their applications. It defines biomaterials as materials that are compatible with living tissues or interact with biological systems. Some key points made include:
- Biomaterials have characteristics of being biocompatible, bioinert or biofunctional.
- Common biomaterials are used in applications like dental implants, hip replacements, and intraocular lenses.
- The properties of biomaterials that are important for their use in the body include mechanical, thermal, electrical, optical and surface properties.
This document discusses tissue engineering and its applications in artificial skin and cartilage. It begins by defining tissue engineering as applying engineering and life science principles to develop biological substitutes that restore or improve tissue function. It then discusses the goals of tissue engineering, including restoring biomechanical and physiological function. The document outlines different types of cells used, including autologous, allogeneic, xenogeneic and stem cells. It provides details on different tissue culture techniques and goes on to describe artificial skin and cartilage, including their history, manufacturing processes, cell sources and advantages/disadvantages.
Tissue reaction to dentofacial orthopedic appliances /certified fixed orthodo...Indian dental academy
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This document summarizes a study on using cell therapy to assist in regenerating cartilage in cases of avascular bone necrosis. It discusses how mesenchymal stem cells derived from bone marrow were used in 15 patients with avascular bone necrosis of the femoral head. The stem cells were isolated from patients' bone marrow and fat tissue then reintroduced with platelet rich plasma. Follow-ups over a year found improved symptoms and radiological signs of new cartilage formation in the patients. The role of the stem cell microenvironment in differentiation is also discussed. The study suggests cell therapy is a promising alternative to traditional surgery for certain orthopedic conditions.
Advancement in Scaffolds for Bone Tissue Engineering: A Reviewiosrjce
In last decade, Tissue Engineering has moved a way ahead and has proposed solutions by replacing
the permanently or severely damaged tissues of our body. The field has expanded to tissue regeneration of
cartilage, bone, blood vessels, skin, etc. The domain of tissue engineering is very wide and is the combination of
bioengineering, biology & biochemistry. This review is focus on recent research advancement in bone tissue
engineering. Bone grafting techniques are used to replace the severely damaged due to any accident, trauma or
any disease. These are either allograft, autologous or synthetic bone properties similar to bone. Bone Tissue
Engineering is part of a synthetic technique and overcome the limitations faced in other two mentioned
techniques. Bone Tissue engineering is rapidly developing field and has become important due to its remarkable
therapeutic properties. Mesenchymal stem cells are used as starting cells in tissue regeneration. These cells get
differentiated into bone cells and start multiplying to form bone. One inevitable requirement of these growing
human cells is a strong support which helps in the proper growth. This support is known as scaffold, in tissue
engineering. For proper regeneration of cells scaffold materials plays vital importance in the field of bone tissue engineering. This review attempts is illustrate the biology of natural bone, various desirable properties of scaffold, biomaterials used for fabrication of scaffold and various fabrication techniques with examples of bone regenerate.
The authors aimed to control the structure of tissue-engineered bone through scaffold design. They seeded human mesenchymal stem cells on silk scaffolds with varying pore sizes using static and dynamic seeding methods. They found that dynamic seeding, where the scaffolds were stirred in a spinner flask, produced bone-like structures that matched the scaffold geometry best. In particular, scaffolds with small pores produced optimal bone growth when seeded dynamically. The experimental design demonstrated the ability to engineer bone-like structures in vitro by controlling scaffold pore size and seeding technique.
Autologous Mesenchymal Stem Cells in OrthopaedicsVladimir Bobic
Nuffield Health, The Grosvenor Hospital Chester, UK
27 June 2013. GP and Physiotherapy Seminar: Autologous Stem Cell Therapies in Orthopaedics. Moderator and Presenter: Vladimir Bobic, Chester Knee Clinic
This document discusses knee cartilage repair technologies and the potential role of stem cells and bone marrow aspirate. It provides an overview of current surgical options for cartilage repair like microfracture and OATS that often have issues with peripheral integration and subchondral support. Finding a biological solution for cartilage regeneration is a major focus of orthopaedic research. Mesenchymal stem cells from bone marrow aspirate show promise but more study is needed. A combined approach of subchondral decompression, bone marrow injection, and osteochondral grafting aims to address both cartilage and subchondral bone issues and may provide better outcomes than addressing cartilage alone.
Craniomaxillofac trauma reconstruction bone graft in cranifacial surgery/oral...Indian dental academy
This document summarizes different types of bone grafts that can be used for craniofacial reconstruction. It discusses autografts, which are obtained from the patient's own bone, including cancellous bone grafts from the iliac crest or cortical bone grafts from the calvarium. The mechanisms by which bone grafts incorporate into the recipient site, including osteoconduction, osteoinduction and osteogenesis, are described. Factors that influence graft incorporation such as graft type, vascularity of the recipient site, and fixation are also reviewed.
Craniomaxillofac trauma reconstr bone graft in cranifacial surgeryIndian dental academy
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Bone physiologynew /certified fixed orthodontic courses by Indian dental acad...Indian dental academy
The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and offering a wide range of dental certified courses in different formats.
Indian dental academy provides dental crown & Bridge,rotary endodontics,fixed orthodontics,
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The document discusses the process of fracture healing. It begins with an inflammatory phase where hematoma forms and inflammatory cells degrade necrotic tissue. This is followed by a reactive phase where new capillaries form granulation tissue (procallus) and osteogenic cells lay down a soft callus of collagen and fibrocartilage. Finally, there is a remodeling phase where the callus is calcified to form hard callus, then remodeled over years into the original bone shape through the action of osteoblasts and osteoclasts. Growth factors and cytokines that regulate each phase of healing are also outlined.
This document summarizes a seminar on bone grafts in hard tissue reconstruction. It discusses the properties, indications, advantages, and disadvantages of various types of bone grafts including autogenous, allogenous, xenografts, and alloplasts. It also describes the principles of bone grafting, factors affecting graft incorporation, classification of grafts, and their mode of action. Specifically, it provides details on autogenous bone grafts including their sources, advantages, and types based on histologic features and vascularity.
Regenerative techniques for periodontal therapyEnas Elgendy
This document discusses graft materials and procedures for restoring periodontal osseous defects, as well as the principles of guided tissue regeneration (GTR). It describes the potential of autografts, allografts, and xenografts to promote osteogenesis, osteoinduction, and osteoconduction. The challenges of transplanting materials into periodontal defects are outlined. Techniques for GTR involve placing barriers to exclude epithelium and favor regeneration. Membranes can be non-resorbable like ePTFE or resorbable like collagen, polyglycolic acid, or polylactic acid polymers. Proper technique and postoperative care are important for successful regeneration.
This document provides an overview of bone biology and its relevance to orthodontics. It discusses the gross anatomy and types of bone, including cortical and trabecular bone. It describes the cells involved - osteoblasts which build bone, and osteoclasts which resorb it. The periodic dental ligament is described as the soft tissue between cementum and alveolar bone. Bone composition, structure, modeling and remodeling processes are summarized. The roles of calcium, phosphorus, collagen and other components are outlined.
Development,structure and organization of boneadityachakri
This document provides an overview of bone development, structure, and types. It discusses that bone is a mineralized connective tissue composed of cells and an intercellular matrix. There are two main types of bone tissue: compact bone, which makes up the hard outer surface and is made up of concentric lamellae; and spongy or cancellous bone, which is found in the interior and has a sponge-like appearance. Bone is also classified based on shape into long, short, flat, irregular, and sesamoid bones. The document outlines the development of bone through two processes: intramembranous ossification which forms flat bones; and endochondral ossification which replaces cartilage models with bone in
This document discusses fracture healing and bone repair. It describes the complex cellular and molecular processes involved, including inflammation, soft and hard callus formation, and remodeling. Failure of healing can occur through atrophic, hypertrophic, oligotrophic, or delayed nonunion. Treatment options to promote healing include autografts, allografts, bone graft substitutes, growth factors, and mechanical or electrical stimulation techniques.
Development of bone
Microstructure of bone
Composition of bone
Formation of osteoblasts
Mineralisation of bone
Formation of osteoclasts
Resorption of bone
Macrostructure of bone
Volume changes in bone
Bone healing
The document discusses the use of bone marrow stromal stem cells (bMSCs) therapy for musculoskeletal problems like discs, cartilage, and bone. It describes a study conducted in rabbits to evaluate the effectiveness of transplanting bMSCs and distracting the intervertebral disc to reverse disc degeneration. The study found that bMSCs transplantation combined with disc distraction led to improved disc height, higher proteoglycan content, and better histological scores compared to other treatment groups. The results suggest that bMSCs transplantation along with increasing disc rehydration through distraction can promote extracellular matrix repair and regeneration for intervertebral disc degeneration.
This document is the thesis of Dongyun Wang for obtaining a Doctor degree from Vrije Universiteit Amsterdam. It discusses developing osteoinductive and antibacterial biomaterials for bone tissue engineering. The thesis contains 7 chapters that investigate enhancing bone regeneration in critical-sized bone defects by introducing osteoinductivity to biphasic calcium phosphate granules, developing a novel bone defect filling material with sequential antibacterial and osteoinductive properties for infected bone defects, and coatings for osseointegration of metallic biomaterials. Funding sources and a list of contents are also provided.
This document discusses the anatomy and types of bone grafts. It begins by describing the two types of bone tissue: cortical/compact bone, which forms the dense outer layer, and cancellous/spongy bone, which fills the interior. Bone grafting is then introduced as a surgical procedure to repair broken or defective bone using donor bone material. The document proceeds to explain the three key processes in bone graft incorporation: osteoinduction, osteoconduction and osteogenesis. It provides details on the types of bone grafts, including those based on donor origin (autograft, allograft, xenograft) and composition (cortical, cancellous). Risks, techniques and applications of different bone graft procedures are
Programmed Assembly of Synthetic Protocells into Thermoresponsive PrototissuesZohaib HUSSAIN
Programmed assembly of synthetic protocells into thermoresponsive prototissues
Programmed assembly of synthetic protocells into thermoresponsive prototissues
Programmed assembly of synthetic protocells into thermoresponsive prototissues
Programmed assembly of synthetic protocells into thermoresponsive prototissues
Programmed assembly of synthetic protocells into thermoresponsive prototissues
Large-scale Production of Stem Cells Utilizing MicrocarriersZohaib HUSSAIN
Large-scale Production of Stem Cells Utilizing MicrocarriersLarge-scale Production of Stem Cells Utilizing MicrocarriersLarge-scale Production of Stem Cells Utilizing MicrocarriersLarge-scale Production of Stem Cells Utilizing MicrocarriersLarge-scale Production of Stem Cells Utilizing MicrocarriersLarge-scale Production of Stem Cells Utilizing MicrocarriersLarge-scale Production of Stem Cells Utilizing MicrocarriersLarge-scale Production of Stem Cells Utilizing MicrocarriersLarge-scale Production of Stem Cells Utilizing MicrocarriersLarge-scale Production of Stem Cells Utilizing Microcarriers
Characterization of Supramolecular PolymersZohaib HUSSAIN
This document discusses several methods for characterizing supramolecular polymers, which are challenging to characterize due to their dynamic nature. Vapor pressure osmometry uses Raoult's law to relate vapor pressure to molecular weight. Theoretical estimation of molecular weight can be obtained from binding constants using equilibrium models. Size exclusion chromatography separates polymers by hydrodynamic radius. Viscometry uses the Mark-Houwink equation to relate intrinsic viscosity to molecular weight. Mass spectrometry, scanning probe microscopy, electron microscopy, and MALDI-TOF mass spectrometry also provide characterization of supramolecular polymers.
Translation initiation in eukaryotes is a highly regulated and rate-limiting process that involves the assembly of numerous transient complexes containing over a dozen eukaryotic initiation factors. This process culminates in the accommodation of a start codon at the appropriate ribosomal site. Structural biology has provided insights into the mammalian mitochondrial translation initiation complex and other key complexes and factors involved in the process, such as eIF3, the eIF2 ternary complex, and the DHX29 helicase. Dysregulation of translation initiation can contribute to diseases like cancer and metabolic disorders.
The document discusses mitochondrial respiratory complexes and respirasomes. It notes that the complexes assemble into larger structures called respirasomes, which are necessary for stable respiratory function. There are four main complexes involved in oxidative phosphorylation. The complexes work together to establish a proton gradient used by ATP synthase to generate ATP. Dysfunction can lead to diseases. Recent cryo-EM studies have provided structural information on respiratory supercomplexes in various organisms, revealing details of protein interactions and organization principles.
PHOTOSYNTHESIS: What we have learned so far? Zohaib HUSSAIN
This document summarizes key information about photosynthesis. It discusses that photosynthesis captures light energy to convert carbon dioxide and water into glucose through chloroplasts in plant leaves. It describes the two stages of photosynthesis - the light-dependent reactions where ATP and NADPH are produced, and the Calvin cycle where glucose is produced. It also discusses C3, C4, and CAM pathways and how plants with different pathways may be impacted by increasing carbon dioxide levels. Potential targets for improving plant photosynthesis through genetic engineering or other methods are also outlined.
Contents
1. Insulin Molecule
2. Effect of Insulin in Body
3. History of Insulin
4. Recent Trends in Insulin Productions and Types
4.1 Animal Insulins
4.2 Long-Acting Insulins
4.3 Human Insulins
4.4 Insulin Analogues
4.5 Biosimilar Insulins
5. Insulin Production (Chain A and Chain B Method)
5.1 Upstream Processing
5.2 Downstream Processing
6. The Proinsulin Process
7. Insulin Available in Market with Different Brand Names
8. References
Oxidation & Reduction involves electron transfer & How enzymes find their sub...Zohaib HUSSAIN
Oxidation is loss of electrons
Reduction is gain of electrons
Oxidation is always accompanied by reduction
The total number of electrons is kept constant
Oxidizing agents oxidize and are themselves reduced
Reducing agents reduce and are themselves oxidized
Cellulase (Types, Sources, Mode of Action & Applications)Zohaib HUSSAIN
Cellulase is an enzyme system consisting of endo- and exo-glucanases and cellobiase that catalyzes the hydrolysis of cellulose. There are three major types of cellulases - endoglucanase, exoglucanase, and beta-glucosidase. Cellulase-producing microbes employ one of three mechanisms: free cellulase systems using individual enzymes, cellulosome complexes, or endoglucanases without other domains. The synergistic action of endo- and exoglucanases supplemented by beta-glucosidase completely degrades cellulose to glucose. Cellulases find applications in food, animal feed, textiles, biofu
Amylases (Types, Sources, Mode of Action & Applications)Zohaib HUSSAIN
Amylases are important hydrolase enzymes which have been widely used since many decades. These enzymes randomly cleave internal glycosidic linkages in starch molecules to hydrolyze them and yield dextrins and oligosaccharides. Among amylases α-Amylase is in maximum demand due to its wide range of applications in the industrial front. α-Amylase can be produced by plant or microbial sources. The ubiquitous nature, ease of production and broad spectrum of applications make α-Amylase an industrially important enzyme.
Life on Earth (By Alonso Ricardo and Jack W. Szostak) Summary (By Zohaib Hus...Zohaib HUSSAIN
Life on Earth (By Alonso Ricardo and Jack W. Szostak)
Summary (By Zohaib Hussain)
Life on Earth (By Alonso Ricardo and Jack W. Szostak)
Summary (By Zohaib Hussain)
Life on Earth (By Alonso Ricardo and Jack W. Szostak)
Summary (By Zohaib Hussain)
Life on Earth (By Alonso Ricardo and Jack W. Szostak)
Summary (By Zohaib Hussain)
Layout of the Cell Culture Room Layout of the Cell Culture Room Layout of the Cell Culture Room Layout of the Cell Culture Room Layout of the Cell Culture Room Layout of the Cell Culture Room Layout of the Cell Culture Room Layout of the Cell Culture Room Layout of the Cell Culture Room Layout of the Cell Culture Room Layout of the Cell Culture Room Layout of the Cell Culture Room Layout of the Cell Culture Room Layout of the Cell Culture Room Layout of the Cell Culture Room Layout of the Cell Culture Room Layout of the Cell Culture Room Layout of the Cell Culture Room Layout of the Cell Culture Room Layout of the Cell Culture Room
1. Levels of gene regulation
The observation that differences in the RNA and protein content of different tissues are not paralleled by significant differences in their DNA content indicates that the process whereby DNA produces mRNA must be the level at which gene expression is regulated in eukaryotes. In bacteria this process involves only a single stage, that of transcription, in which RNA copy of the DNA is produced by the enzyme RNA polymerase. Even while this process is still occurring, ribosomes attach to the nascent RNA chain and begin to translate it into protein. Hence cases
of gene regulation in bacteria, such as the switching on of the synthesis of the enzyme β-galactosidase in response to the presence of lactose (its substrate), are mediated by increased transcription of the appropriate gene. Clearly, a similar regulation of gene transcription in different tissues, or in response to substances such as steroid hormones which induce the synthesis of new proteins, represents an attractive method of gene regulation in eukaryotes.
In contrast to the situation in bacteria, however, a number of stages intervene between the initial synthesis of the primary RNA transcript and the eventual production of mRNA (Fig. 1).
The initial transcript is modified at its 5′ end by the addition of a cap structure containing a modified guanosine residue and is subsequently cleaved near its 3′ end, followed by the addition of up to 200 adenosine residues in a process known as polyadenylation. Subsequently, intervening sequences or introns, which interrupt the protein-coding sequence in both the DNA and the primary transcript of many genes. Although this produces a functional mRNA, the spliced molecule must then be transported from the nucleus, where these processes occur, to the cytoplasm where it can be translated into protein.
Telomere, Functions & Role in Aging & CancerZohaib HUSSAIN
Telomeres cap the ends of chromosomes and protect them from degradation during cell division. As cells divide, telomeres shorten due to the inability of DNA replication enzymes to fully copy chromosome ends. This limits a cell to around 50-70 divisions before entering senescence. Cancer cells activate telomerase to maintain telomere length, allowing unlimited division. Telomeres play a key role in both aging and cancer - their shortening limits the lifespan of normal cells but cancer cells overcome this via telomerase to achieve immortality and uncontrolled growth. Measuring and targeting telomerase may provide new strategies for cancer detection and treatment.
Eukaryotic and Prokaryotic Chromosomes Eukaryotic and Prokaryotic Chromosomes Eukaryotic and Prokaryotic Chromosomes Eukaryotic and Prokaryotic Chromosomes Eukaryotic and Prokaryotic Chromosomes Eukaryotic and Prokaryotic Chromosomes Eukaryotic and Prokaryotic Chromosomes
Chromosomes are bundles of tightly coiled DNA located within the nucleus of almost every cell in our body. A chromosome is a DNA molecule with part or all of the genetic material (genome) of an organism. Chromosomes are normally visible under a light microscope only when the cell is undergoing the metaphase of cell division. Before this happens, every chromosome is copied once (S phase), and the copy is joined to the original by a centromere, resulting in an X-shaped structure. The original chromosome and the copy are now called sister chromatids. During metaphase, when a chromosome is in its most condensed state, the X-shape structure is called a metaphase chromosome.
Chemical Modifications of Protein and its Applications Zohaib HUSSAIN
This document discusses chemical modifications of proteins. Chemical modifications can be done intentionally to study structure-function relationships, develop new products, or improve existing ones. Modifications are used in fields like pharmacology, food production, and industry. Specific modifications discussed include sulfhydryl and disulfide modifications by oxidation, and reduction of disulfide bonds. Applications mentioned are in basic protein chemistry, food and nutrition to prevent deterioration or alter properties, and pharmaceuticals to alter biological properties, target drug delivery, or influence drug lifetime in the body.
Chair and Presenter, Stephen V. Liu, MD, Benjamin Levy, MD, Jessica J. Lin, MD, and Prof. Solange Peters, MD, PhD, discuss NSCLC in this CME/MOC/NCPD/AAPA/IPCE activity titled “Decoding Biomarker Testing and Targeted Therapy in NSCLC: The Complete Guide for 2024.” For the full presentation, downloadable Practice Aids, and complete CME/MOC/NCPD/AAPA/IPCE information, and to apply for credit, please visit us at https://bit.ly/4bBb8fi. CME/MOC/NCPD/AAPA/IPCE credit will be available until July 1, 2025.
Why Does Seminal Vesiculitis Causes Jelly-like Sperm.pptxAmandaChou9
Seminal vesiculitis can cause jelly-like sperm. Fortunately, herbal medicine Diuretic and Anti-inflammatory Pill can eliminate symptoms and cure the disease.
Causes Of Tooth Loss
PERIODONTAL PROBLEMS ( PERIODONTITIS, GINIGIVITIS)
Systemic Causes Of Tooth Loss
1. Diabetes Mellitus
2. Female Sexual Hormones Condition
3. Hyperpituitarism
4. Hyperthyroidism
5. Primary Hyperparathyroidism
6. Osteoporosis
7. Hypophosphatasia
8. Hypophosphatemia
Causes Of Tooth Loss
CARIES/ TOOTH DECAY
Causes Of Tooth Loss
CAUSES OF TOOTH LOSS
Consequence of tooth loss
Anatomic
Loss of ridge volume both height and width
Bone loss :
mandible > maxilla
Posteriorly > anteriorly
Anatomic consequences
Broader mandibular arch with constricting maxilary arch
Attached gingiva is replaced with less keratinised oral mucosa which is more readily traumatized.
Anatomic consequences
Tipping of the adjacent teeth
Supraeruption of the teeth
Traumatic occlusion
Premature occlusal contact
Anatomic Consequences
Anatomic Consequences
Physiologic consequences
Physiologic Consequences
Decreased lip support
Decreased lower facial height
Physiologic Consequences
Physiologic consequences
Education of Patient
Diagnosis, Treatment Planning, Design, Treatment, Sequencing, and Mouth Preparation
Support for Distal Extension Denture Bases
Establishment and Verification of Occlusal Relations and Tooth Arrangements
Initial Placement Procedures
Periodic Recall
Education of Patient
Informing a patient about a health matter to
secure informed consent.
Patient education should begin at the initial
contact with the patient and should continue throughout treatment.
The dentist and the patient share responsibility for the ultimate success of a removable partial denture.
This educational procedure is especially important when the treatment plan and prognosis are discussed with the patient.
Diagnosis, Treatment Planning, Design, Treatment, Sequencing, and Mouth Preparation
Begin with thorough medical and dental histories.
The complete oral examination must include both clinical and radiographic interpretation of:
caries
the condition of existing restorations
periodontal conditions
responses of teeth (especially abutment teeth) and residual ridges to previous stress
The vitality of remaining teeth
Continued…..
Occlusal plan evaluation
Arch form
Evaluation of Occlusal relationship through mounting the diagnostic cast
The dental cast surveyor is an absolute necessity in which patients are being treated with removable partial dentures.
Mouth preparations, in the appropriate sequence, should be oriented toward the goal of
providing adequate support, stability,
retention, and
a harmonious occlusion for the partial denture.
Support for Distal Extension Denture Bases
A base made to fit the anatomic ridge form does not provide adequate support under occlusal loading.
The base may be made to fit the form of the ridge when under function.
Support for Distal Extension Denture Bases
This provides support
Exploring Alternatives- Why Laparoscopy Isn't Always Best for Hydrosalpinx.pptxFFragrant
Not all women with hydrosalpinx should choose laparoscopy. Natural medicine Fuyan Pill can also be a nice option for patients, especially when they have fertility needs.
Mainstreaming #CleanLanguage in healthcare.pptxJudy Rees
In healthcare, every day, millions of conversations fail. They fail to cover what’s really important, fail to resolve key issues, miss the point and lead to misunderstandings and disagreements.
Clean Language is one approach that can improve things. It’s a set of precise questions – and a way of asking them – which help us all get clear on what matters, what we’d like to have happen, and what’s needed.
Around 1000 people working in healthcare have trained in Clean Language skills over the past 20+ years. People are using what they’ve learnt, in their own spheres, and share anecdotes of significant successes. But the various local initiatives have not scaled, nor connected with each other, and learning has not been widely shared.
This project, which emerged from work done by the NHS England South-West End-Of-Life Network, with help from the Q Community and especially Hesham Abdalla, aims to fix that.
JMML is a rare cancer of blood that affects young children. There is a sustained abnormal and excessive production of myeloid progenitors and monocytes.
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1. Bone Tissue Engineering
Zohaib Hussain
Tissue Engineering
Professor Dr Giyoong Tae
School of Materials science and Engineering
Gwangju Institute of Science and Technology
2. • Introduction
• Anatomy and Physiology of bone
• Bone Tissue Engineering
• Recent studies related to bone tissue engineering
• Commercialized products and ongoing clinical trials
• Biomedical start-ups
• Concluding remarks
Contents
3. Introduction and Motivation
The global market for bone grafts and substitutes now
exceeds US$2.5 billion, including over US$500 million
for dental and craniofacial applications
4. Autologous bone grafts - The "gold standard" - a procedure where bone is relocated from one organ to another in the
patient's body. Autologous bone grafting currently accounts for about 40% of all bone reconstruction procedures.
Limitations:
- An invasive surgical procedure
- Donor site morbidity
- Insufficient graft volume
- Poor graft quality
Allogeneic/xenogenic bone grafts - These grafts are obtained from human cadavers, living donors or animal sources.
DBM (Demineralized Bone Matrix) is employed which is produced by partial dissolution of bone tissue and consequent
gain of vital organic ingredients that support bone cells.
Limitations:
- Suitable for small bone defects
- Inferior bone properties
- Risk of infection
- Long recovery
The ideal bone graft substitute must demonstrate biocompatibility, functional and structural similarity to the
defective or deficient bone, ease of use and cost-effectiveness.
Treatments
9. Short, irregular, and flat bones all consist of thin plates of
spongy bone covered by compact bone. There is no well-
defined cavity for the marrow to sit in, and hyaline cartilage
covers portions of the surface that are involved with joints.
Compact bone, which is very dense and smooth.
Inside there is lots of spongy bone, which is like a
honeycomb of little needles. Typically the open
spaces will be filled with bone marrow. The precise
arrangement of compact and spongy bone depends
on the bone type.
11. Periosteum - the fibrous membrane
cover the outer surface of the bone. It
has blood vessels, nerves, lymphatic
vessels that nourish the compact bone. -
covers the entire outer surface of the
bone, outer surface of the bone except
at the epiphysis region where it has
articular cartilage. this acts as the shock
absorber and reduces the friction.
Endosteum-place for bone growth, repair and
remodeling
12. Flat bones: Cranium it is made up of a layer of a
spongy bone and lined on either side of the layer
of the compact bones. So, the layer of spongy
bone and the two layers of the compact bone
works together to protect the internal organs. If
there is any fracture in the outer cranial bone still
the brain is protected by the inner contact layer
of the compact bones.
Three general classes of bone markings: (1)
articulations, (2) projections, and (3) holes
13. Question: Both osteocyte and osteoblast lack mitosis, then there rise
the question, if both the cells lack mitosis how are they replenished
when old one dies?
Answer: Osteogenic cell. It is the only bone cell that can divide, it
divide and differentiate into osteoblast cells.
14. Osteon is made of a series of lamellae, which are hollow tubes, Within each
lamella are collagen fibers running in a specific direction, with crystals of bone
salts in between. This alternating pattern is what gives compact bone the ability
to withstand torsion or twisting force
Spongy bone is not made up of concentric rings whereas it
is made up of lattice like network of matrix spikes called
trabeculae. This provides strength to the bone, the spaces in
some spongy bones which that contains red marrow which
are protected by the trabeculae where haematopoiesis
occurs.
15. The spongy bone and medullary cavity receive nourishment from arteries that
pass through the compact bone.
Enter through the nutrient foramen which is the small opening that present in
the diaphysis.
The osteocytes present in the spongy bone get nourished by the blood vessels
and the arteries that enter through the periosteum and into the marrow cavities.
Nerves tend to concentrate in the more metabolically active regions of the bone.
Nerves also sense pain; the nerves also plays a very important role in regulating
blood supplies and bone growth.
Blood and nerve supply
16. Two Pathways
Intramembranous pathway and endochondral
pathway
In first intramembranous bone where
mesenchymal stem cells are directly developed
into osteoblast cells and subsequent bone
formation occurs.
In endochondral bone endochondral the
mesenchymal progenitor cells developed into
chondrocytes, first they are developed into
chondrocytes. Then they form a cartilaginous
layer, cartilaginous matrix, calcified matrix, then
they subsequent bone formation occurs.
Bone development “modeling”
Aghajanian, P., Mohan, S. The art of building bone: emerging
role of chondrocyte-to-osteoblast transdifferentiation in
endochondral ossification. Bone Res 6, 19 (2018).
22. Timeline of major milestones in biomaterials design for bone-tissue engineering
Koons, G.L., Diba, M. & Mikos, A.G.
Materials design for bone-tissue
engineering. Nat Rev
Mater 5, 584–603 (2020).
https://doi.org/10.1038/s41578-
020-0204-2
27. Common material types for bone- tissue engineering
Biosynthetic substitutes - synthetic or natural
biomaterials that promote bone regeneration.
Limitations:
- Inferior bone properties
- Suitable for small bone defects
- Long recovery
31. PCL and PCL composites (PCL–HA, PCL/TCP, etc.) obtained by
Fused Deposition Modelling (FDM) These so-called first-
generation scaffolds have been studied for more than 5 years
in a clinical setting, have been commercialized
(http://www.osteoporeinternational.com) and have gained
Federal Drug Administration (FDA) approval. Schantz et al.
(2006) used FDM-fabricated PCL scaffolds as burr hole plugs in
a pilot study for cranioplasty. The clinical outcome after 12
months was positive, with all patients tolerating the implants,
no adverse side-effects reported and good cosmetic and
functionally stable cranioplasty observed in all cases.
Same group studied
mPCL–CaP composite
scaffolds for cranial,
osteochondral and spinal
fusion in animal models
1st and 2nd Generation scaffolds for bone tissue engineering
32. Liu, M., Zeng, X., Ma, C. et al. Injectable hydrogels for
cartilage and bone tissue engineering. Bone Res 5, 17014
Injectable hydrogels for bone tissue-engineering applications
33. Macrophage-derived small extracellular vesicles promote biomimetic mineralized
collagen-mediated endogenous bone regeneration
Liu, A., Jin, S., Fu, C. et al. Macrophage-derived small extracellular vesicles promote biomimetic mineralized collagen-
mediated endogenous bone regeneration. Int J Oral Sci 12, 33 (2020)
35. Highly osteogenic MSC line generated from induced
pluripotent stem cells that generates high yields of
an osteogenic cell-matrix (ihOCM) in vitro.
The intrinsic osteogenic activity of ihOCM surpasses
bone morphogenic protein 2 (BMP2) driving healing
of calvarial defects in 4 weeks by a mechanism
mediated in part by collagen VI and XII. We propose
that ihOCM may represent an effective replacement
for autograft and BMP products used commonly in
bone tissue engineering.
b High-power micrographs of healed specimens indicating
trabecular micro-structure of newly formed bone (bar = 75 μm).
Yellow boxes in panel a indicate the enlarged region in
panel b. c Healing index of defects.
McNeill, E.P., Zeitouni, S., Pan, S. et
al. Characterization of a pluripotent stem cell-
derived matrix with powerful osteoregenerative
capabilities. Nat Commun 11, 3025 (2020).
https://doi.org/10.1038/s41467-020-16646-2
Characterization of a pluripotent stem cell-derived matrix with powerful osteoregenerative
capabilities
36. Graphic representation of the ultrasound-mediated gene
therapy for segmental bone repair. (1) Non-union bone
fracture. (2) Collagen sponge insertion. (3) Stem cell migration
into the sponge (4) Injection of microbubbles and therapeutic
gene. (5) Sonoporation/Ultrasound application.
Bone grafting can be complicated, as bone
cells are not always available and their harvest,
usually from the pelvic bone, can lead to
prolonged pain.
The Gazit Laboratory is developing a novel
approach for the treatment of bone fractures
without the need for bone grafting.
Targeting of Endogenous Stem Cells for Segmental Bone
Fracture Repair
Sci Transl Med. 2017 May 17; 9(390):pii:eaal3128.
38. Commercial product
(name)
Substitute materials Properties Applications
Osteograf Ceramic
Osteoconductive, limited osteoinductive
when mixed with bone marrow
Bone void filler
NovaBone Bioactive glass
Osteoconductive, limited osteoinductive
when mixed with bone marrow
Filling surgical or traumatic bone gaps
Osteosat Surgical grade calcium phosphate Osteoconductive and bioresorbable Hip and knee joint repair
Calceon 6 Calcium sulfate Osteoconductive and bioresorbable Bone void filler; provides strength
Norian
Monocalcium phosphate, tricalcium phosphate, and
calcium carbonate
Good compressive strength
Skull bone defect; injectable paste,
craniofacial reconstructions
Hard tissue-replacement
(HTR)
Poly methyl methacrylate (PMMA)
Good strength, durable, and surface
osteoconductive
Craniofacial reconstruction
Alpha BSM Calcium phosphate cement Good compressive strength
Dental application for bone and cartilage
defects
Mimix Synthetic hydroxyapatite tetra-tricalcium phosphate Good compressive strength Cranial defects
ELIZ (Kyeron)
Composed of (40%) β-tricalcium phosphate and of
(60%) hydroxyapatite
Ultrahigh porosity, biocompatible, and
osteoconductive
It has been successfully implanted in
more than 1200 patients without any
side-effects.
OSIQ (Kyeron) Fully synthetic ultrapure nano-hydroxyapatite
Ready to use, injectable, and
biodegradable
Filling or reconstruction of small and
medium bone defects
AXOZ QS (Kyeron)
Resorbable phosphocalcic compounds and a
polymer
Injectable and fully resorbs Supports bone growth
COLLAPAT II (Symatese)
Composed of a collagen structure in which
ceramised hydroxyapatite granules are dispersed
Strong hemostatic power, completely
resorbable in a few weeks, and
osteoconductive
Induces bone substance replacement in
maxillofacial surgery and
odontostomatology
CopiOs (Zimmer Biomet)
Bone Void Filler
Calcium phosphate, dibasic (DICAL), and highly
purified Type I bovine collagen
DICAL provides significantly more
calcium and phosphate ions at
equilibrium than either β-TCP or HA
CopiOs paste acts as an osteoconductive
scaffold for the growth of new bone
List of some commercially available synthetic materials and their applications.
Dahiya, U. R., Mishra, S., & Bano, S. (2019). Application of Bone Substitutes and Its Future Prospective in Regenerative Medicine. In Biomaterial-
supported Tissue Reconstruction or Regeneration. IntechOpen.
39. Commercial
product (name)
Substitute material Properties Applications
Cortoss
Polymer system with
reinforcing particle bioactive
glass
Forms biological interface
Augmentation of screws in
osteoporotic bone (hip,
spine, etc.)
Open porosity
polylactic acid
polymer (OPLA)
Polylactic acid
Osteoconductive and
bioresorbable
Articular cartilage
regeneration
Collagraft
Mixture of tricalcium
phosphate, bovine collagen,
and hydroxyapatite
Bioresorbable and
osteoconductive
Use for the treatment of
long bone fracture and
void filling
DynaGraft Demineralized bone matrix
Heat sensitive copolymer,
injectable gel, limited
osteo-induction
Dental bone graft
substitute
MedPor Porous polyethylene Higher porosity
Orbital reconstruction and
facial contouring
Collapro/matrix
Human collagen in lyophilized
strip
Lack of immunogenic
property
Use in development
Healos
Hyaluronic acid-coated
collagen sponge
Osseo-inductive property
Replacement of
autograft/autograft
extender for spinal fusion
Immix
PGA/PLA polymer to be
produced in chip, flex forms
Provides structural
support
Bone graft extender
OsteoScaf (Bonetec)
Macroporous poly(lactide-co-
glycolide)/calcium phosphate
(PLGA/ CaP) foam matrices
Fully resorbable,
osteoconductive, and
mechanically robust
Heal tissue defects
List of some commercially available polymer-based graft materials and their applications.
Dahiya, U. R., Mishra, S., & Bano, S. (2019). Application of Bone Substitutes and Its Future Prospective in Regenerative Medicine. In Biomaterial-
supported Tissue Reconstruction or Regeneration. IntechOpen.
40. A Tailor-made bone graft:
Personalized bone regeneration by using culture expanded autologous cells and
biomaterials
The cells autlogous (self) origin eliminates the risk of tissue rejection and surgery failure. The adipose tissue required for
the production of adipose-derived cells is harvested in a simple and minimally invasive procedure.
The scaffold's unique nano-structure optimally supports cell expansion in vitro (in the laboratory) and provides the desired
supporting properties in vivo (in the patient).
Personalized, available-on-demand product aimed to treat a variety of bone and joint conditions. It is individually designed
to precisely fit the anatomical shape of the bone void in question.
Growing trend and advanced approach
41. Injectable bone graft:
Provided in a pre-filled syringe containing bone-
inducible cell-seeded matrix particles. This product is
suitablee for well-defined bone repair applications
such as jaw bone cysts
Anatomically pre-designed bone graft:
The scaffold is cut to precisely match the patient's 3D
Computed Tomography (CT) image. This product aims
to repair large/ segmental bone defects.
BonoFillTM is currently being performed in phase I/II clinical study, for maxillofacial bone augmentation
and regeneration.
https://www.bonusbiogroup.com/index.php/products/bonofill
42. Personalized maxillary bone regeneration by using culture expanded autologous bone marrow stem cells and
biomaterials
https://www.maxibone.eu/page-d-exemple/about-maxibone/
Sarted in January 2018 as a four year program with an European funding of 6 million euros. The consortium gathers 12 partners from 6
European countries including research laboratories, academic hospitals, cell therapy units, an SME manufacturing biomaterials and the global
leader of dental implants.
The FP7-Reborne project, a phase 2 clinical trial, received European funding from 2010 to 2015.
The H2020-Maxibone project, a phase 3 clinical trial, has received two European grants and is scheduled to start in early 2019.
43. Next 21 K.K. to commercialize CT Bone, 3D printed bone grafts, in Japan, Europe and other Asian countries
•
3D Printed Bone Grafts – Japan-based Next 21 K.K. received formal approval from Ministry of Health, Labor and Welfare (MHLW) to 3D print synthetic
bone grafts made of calcium phosphate, called CT Bone, for patients
•Accurate and Compatible – 3D printing allows bone grafts to be made with 0.1 millimeter accuracy, with curing method applied so material can assimilate
with patient’s existing bone quickly
•Study Results – 3D printed implants were placed on 23 sites for 20 patients with facial bone deformities and results show sufficient bone union in 19 sites
with no serious defects and no change observed in shape of CT bones
•Commercialization – Company to commercialize technology in Japan and other Asian countries, and will work with Dutch company Xilloc on licensing to
expand manufacturing and sales in Europe
CT-Bone®
CT-Bone® is not yet available. CT-Bone® is a 3D printed calcium
phosphate that unifies with the patient’s bone. It can be used
for bony augmentations (non-load-bearing) and is converted
into real bone in the patient. Because it is 3D printed it can be
made into complex shapes with controlled porosity. Autoclave
(steam) sterilisation.
Histological investigations showed that in the
hydroxyapatite, bone-like tissue was only found in
some micropores close to the surface. In CT-Bone®,
large bone-like tissues penetrated into the
macropores, containing activated osteoclasts,
fibroblasts and even blood vessels. In addition, bone
marrow formation was observed containing
erythroblasts and megakaryocytes.
44. Grow bones from your own cells: EpiBone is developing technology to create bone tissue from a patient's mesenchymal
stem cells in vitro for use in bone grafts.
https://www.epibone.com/technology/
45. The ideal bone graft substitute must demonstrate biocompatibility, functional and structural similarity to the
defective or deficient bone, ease of use and cost-effectiveness.
Bone tissue engineering has been developed as a promising alternative to bone grafting and as a solution exhibiting
the three required processes of bone healing: osteogenesis, osteoinduction and osteoconduction.
Current limitations:
Identification of the ideal cell population for transplantation
Inefficient procedures for cell isolation
Expansion on the scaffold
Preparation for grafting
Lack of sufficient and timely vascularizations
To address the limitations of existing bone regeneration therapies, multidisciplinary team of scientists, engineers,
clinicians need to work together to design strategy that precisely fit the patients needs and feature all ideal bone
graft characteristics.
Concluding Remarks
46. Thank you so much; If you have any question please ask
Editor's Notes
Bones can be placed into two categories, axial and appendicular.
Axial bones are found in the head and torso, making up the spine, rib cage, and skull.
Appendicular bones make up our appendages, or limbs, those being the arms and legs, as
well as the pelvis and shoulders.
Bones can also be classified by shape, being either long, short, flat, or irregular.
Long bones are longer than they are wide, like the ones in our limbs.
Short bones are cubelike, found in the ankles and wrists among other places.
Flat bones are thin and often curved, like the sternum and shoulderblades.
And irregular bones are the ones that have complicated shapes that don’t fit into the
other three categories, like vertebrae and hip bones.
Bones protect organs
Bones support body
Bones act as lever
Mineral storage ca and p enter into blood stream when required
Fat sotrgae
Harmone production
Blood cell formation
Schematic illustration of a distinct hierarchical structure of bone tissue. (a)At the macrostructural level, bone is composed of cortical bone and cancellous bone. (b) At the microstructural level, the cortical bone is made up of repeated units of osteon, which is characterized by 20–30 concentric layers of collagen fibers, called lamellae. The lamellae surround the central canal and contain various blood vessels and nerves. (c) At the nanostructural level, there are large numbers of collagen fibers, which are composed of periodic collagen fibrils and gaps between the collagen molecules. The calcium phosphate crystals and non-collagenous organic proteins are embedded in these gaps between collagen molecules.76
We will have to examine bones at a few levels of complexity, starting with gross anatomy,
meaning the part that is visible to the naked eye.
The outer layer of any bone is made of
Long bones are a little different.
These contain a tubular shaft, called a diaphysis.
This is made of a thick collar of compact bone surrounding a medullary cavity, or marrow cavity.
In adults, this cavity contains yellow bone marrow which is high in fat.
The ends of a long bone are called epiphyses.
These parts do contain spongy bone inside the compact bone, and again, cartilage covers
the joint surface for cushion and stress absorption.
Beyond the yellow marrow we mentioned, there is also red marrow, which can be found inside
the cavities of spongy bone, and this type of marrow produces blood cells.
We can also see an epiphyseal line, which is a remnant of the epiphyseal plate, a disc
of cartilage that grows during childhood, which is how these bones get longer as a child
gets taller.
A white membrane called the periosteum covers the exterior of the bone, consisting of an
outer fibrous layer made of dense irregular connective tissue, and an inner osteogenic
layer, containing primitive stem cells.
This membrane is attached to a network of nerve fibers and blood vessels, which then
pass through the shaft to the marrow cavity, and perforating fibers connect the periosteum
to the bone.
Endosteum covers the internal spongy bone layer, as well as canals that pass through
the compact bone.
Now that we have this view covered, let’s zoom in a little more and check out the microscopic
anatomy of a bone.
We can find a few different types of cells in here, so let’s go through each one.
First, osteogenic cells.
These are a type of stem cell that actively divide, and they are found in the periosteum
and endosteum that we mentioned.
If the bone is growing, these are flattened or squamous cells, and they can differentiate
into other types at certain times.
Next are osteoblasts.
These are the ones that secrete the bone matrix that consists of collagen and other proteins,
meaning they are responsible for bone growth.
These are also actively mitotic, and cube-shaped while active.
Once surrounded by matrix, they become our next type of cell, osteocytes.
These are mature bone cells that monitor and maintain the bone matrix, communicating this
information to other cells.
Next are bone lining cells, which are flat cells found on the surface of the bone.
These also help maintain the matrix.
And lastly, osteoclasts.
These are large cells with multiple nuclei that use enzymes to break down bone, which
is a normal process called resorption that releases minerals to be transferred to the blood.
an articulation is where two bone surfaces come together (articulus = “joint”). These surfaces tend to conform to one another, such as one being rounded and the other cupped, to facilitate the function of the articulation. A projection is an area of a bone that projects above the surface of the bone. These are the attachment points for tendons and ligaments. In general, their size and shape is an indication of the forces exerted through the attachment to the bone. A hole is an opening or groove in the bone that allows blood vessels and nerves to enter the bone. As with the other markings, their size and shape reflect the size of the vessels and nerves that penetrate the bone at these points.
Osteoblasts cells are the bones cells responsible for the formation of bone. It
is present in the growing structures and it is called osteocyte and which is the primary
cell for the mature bone. And, the places where the osteocytes located are called as
lacunae. Osteocytes maintain the mineral concentration within the matrix. Osteoblast and osteocytes
communicate with each other and exchange their nutrients through the long cytoplasmic processes
via canaliculi which is canaliculus which is present inside the bone matrix. Both osteocyte
and osteoblast lack mitosis, then there rise the question, if both the cells lack mitosis
how are they replenished when old one dies? The answer lies in the third category, third
property of cell which is osteogenic cell. It is highly undifferentiated cell and it
is present in the deep marrow present in the deeper regions of periosteum and marrow cavities.
It is the only bone cell that can divide, it divide and differentiate into osteoblast
cells. So, while explaining the function of bone the last function where I said bonus
is dynamic in nature, which means the new bone is constantly formed and the old bone
that or the damaged bone or the repaired bone should be resorbed continuously, which was,
which is done by the cells called osteoclast cells. Osteoclast cells are responsible for
bone resorption. So, there should be a constant balance between
osteoblast cells which are responsible for the formation of new bone and osteoclast cells
which are responsible for the bone resorption in order to maintain the structural integrity
of the bone.
So, this reviews the cell type, its function and location in the bone. First cell type
is osteogenic cells, as I said it is the only cell that can divide and it develop into osteoblast.
It is present in the deep layers of periosteum and the marrow. And, the next is osteoblasts
cells which are responsible for the formation of bone and present in the growing portions
of bone including periosteum and endosteum. Osteocytes which are the primary cell for
a matured bone and the location where it is located it is known as lacunae.
And, it maintains the mineral concentration of matrix which are entrapped in matrix. Osteoclasts
cells are responsible for bone resorption and it is present at the bone surfaces and
at sites of old injured or unneeded bone. These osteoclasts cells are formed from monocytes
or macrophages which are two white blood cells, they are not originated from osteogenic cells.
First let’s check out the compact bone in the shaft.
This is actually not solid all the way through, there are many cylindrical units with open
canals at the center, and each of these units is called an osteon.
If we were to pull one of these out of the bone, we would see that it is made of a series
of lamellae, which are hollow tubes, and these are arranged like the rings of a tree trunk.
Within each lamella are collagen fibers running in a specific direction, with crystals of
bone salts in between, and as we proceed inward, the next lamella will have its fibers running
in another direction, continuing in this fashion all the way to the center.
This alternating pattern is what gives compact bone the ability to withstand torsion, or
twisting force.
The open region at the center is called the central canal, and it contains blood vessels
and nerve fibers that serve the cells in that osteon.
There are also shorter canals running perpendicular, allowing for connections to run all the way
from the periosteum to the central canals to the medullary cavity.
Where the lamellae meet we can find tiny gaps called lacunae, and these are filled with
osteocytes.
The lacunae are connected by extra-tiny canals called canaliculi.
Beyond the lamellae found within osteons, there are others called interstitial lamellae,
that fill in gaps between osteons, as well as circumferential lamellae, which make up
the circumference of the diaphysis, surrounding all the osteons.
a Endochondral ossification. Mesenchymal stromal cells develop into two different lineages, chondrogenic and osteogenic with no other intermediates. b Intramembranous ossification. Osteoblast development does not require the formation of a chondrocyte template. Mesenchymal stromal cells directly differentiate in an osteogenic lineage. c Chondrocyte to osteogenic precursor. Immature chondrocytes differentiate into an osteogenic precursor population which then differentiate into pre-osteoblasts and osteoblasts. d Dedifferentiation to redifferentiation. Hypertrophic chondrocytes dedifferentiate into immature chondrocytes, which directly differentiate to an osteogenic fate. e Direct transdifferentiation. Hypertrophic chondrocytes directly differentiate to osteoblasts.
Then the remodelling of bone takes place, we know that the skeleton is a metabolically
active organ that undergoes continuous remodelling throughout the life. This remodelling is necessary
in order to maintain the structural integrity as well as to maintain the mineral concentration
within the matrix. Remodelling of bone begins at the early fetal stage and also once the
skeleton is fully formed in young adults, afterwards all the metabolic activity will
takes place in this form.
This remodelling consists of highly regulated series of; this consists of series of highly
regulated steps which involves the interaction of two cell lineages, two cell lineages.
They are mesenchymal osteoblastic cells and hematopoietic osteoclastic cells. The interaction
between mesenchymal osteoblastic cells and hematopoietic osteoclastic cells precursors
cells leads the it the start of the remodeling phase. And, there are four phases in remodelling
of a bone: activation phase, resorption phase, reversal phase and formation of the phase.
The first phase is the activation phase where the interaction between the two precursors
cell lines happens. So, which results in the formation, differentiation, fusion of and
formation of the large osteoclasts cells. Osteoclast cells which are present at the
surface of the bone matrix, these cells will tend to secrete hydrogen ions, hydrogen ions
as well as the lysosomal enzymes. Especially cathepsin C, cathepsin K; cathepsin K these
two will degrade all bone cellular components including collagen at low pH. And, this is
the resorption phase, the resorption phase where the cells interact with the hematopoietic
precursors to form osteoclasts and the reversal phase the complete resorption takes place.
The complete resorption of bone by osteoclasts takes place in the reversal phase and initiates
the formation phase. In this formation phase, mesenchymal osteoblastic
cells will form, will start to produce osteoblasts, which which fills the cavity which are resorbed
by the osteoclasts thereby it laid down the bone matrix. So, this how the remodelling
of bone occurs; the first is the interaction of between two precursors cell lines which
is hematopoietic osteoclasts cell and mesenchymal osteoblasts. And then they form the osteoclasts
cells. This osteoclast cell involve in bone resorption and it resorbs the bone matrix
completely whereas, there is an formation of osteoblast cells which fills the cavity
of the bone resorbed matrix. So, this is how bone modelling and remodelling, formation
of bone occurs.
If there are any abnormalities present in this bone remodelling will lead to various
skeletal disorders. For example, osteoporosis, hypothyroidism and hyperthyroidism, hyperparathyroidism
and hyperthyroidism, Paget disease, orthopaedic disorders, osteopetrosis. These are the skeleton
disorders which are due to abnormalities happen in the bone remodelling cycle. So, osteoporosis
- osteoporosis is defined as the loss of bone mass and strength which leads to the increase
in propensity to fracture. It is type 1 and type 2; type 1 is called as postmenopausal
osteoporosis and type 2 is called as senile osteoporosis.
Recently studies have, literature have proved that deficiency of oestrogen which is the
important systemic hormone for the bone turnover; if there is deficiency of oestrogen it leads
to osteoporosis. So, this deficiency or the osteoporosis reasons can be mainly due to
three reasons; one the peak, peak bone mass is not formed completely or there is a imbalance
between osteoclast function and osteoblast function or the over activeness of osteoclast.
Like over osteoclasts are activated too much thereby it resorbs bone more than the bone
formation, that is osteoporosis. And, Paget disease again they complete mechanism or the
clear mechanism is not yet understood. But, they say that the because of some viral
infection this osteoclast cells are activated abnormally and thereby bone resorption is
more, where it changes the structural structure of the bone, where it shows in the evident
in that picture that is Paget disease. In osteopetrosis, osteoblasts function is lost,
loss of osteoblast function; bone formation is not that great when compared to bone resorption.
So, there should be a balance between the formation of bone or the resorption of bone,
in order to maintain a proper shape of the bone; otherwise it will lead to a variety
of skeletal disorders.
is any fracture, bone can itself heal by its process. It can be repaired by the process
of both intra membranous and endochondral bone formation. It first it starts with the
hematoma formation accompanied by the inflammatory response, then it start recruiting the signalling
molecules. For example: interleukin, fibroblast growth factors, bone morphogenetic proteins
which are responsible for the formation of bone.
Once after recruiting signalling molecules at the place of cortex and periosteum intra
membranous formation, bone formation immediately occurs. Then it stabilizes the fracture by
the formation of callus which is under which with by chondrogenesis. Chondrogenesis is
the activation of chondrocytes which is highly similar to endochondral ossification.
Then once the tissue reaches its maturity, the chondrocyte proliferation decreases and
they calcify the matrix, the growing blood vessel which carries chondroclasts and osteoblastic
progenitors. This chondroclasts will resorb the calcified cartilage and whereas, the osteoblastic
progenitors will helps in the formation of new bone and the remodelling of new bone will
starts; so, thus by it heals the repair or fracture.
As we know that bone is highly vascularized tissue, though it can heal by itself beyond
certain point or beyond critical point clinical intervention is required; where the future
treatment option is bone tissue engineering. Bone tissue engineering is considered to be
the future treatment option. In next session we will be discussing about is status or key
components involved in the bone tissue engineering. Thank you.
. Initial efforts towards bone repair involved the use of calcium phosphates and bioresorbable metals, which were followed by observations of bone formation in polymeric materials and the invention of Bioglass, the first human- made material capable of bonding to living tissues. Further work led to the identification of bioactive molecules such as proteins and peptides, after which bone-tissue engineering emerged as a separate research field. Subsequently, scaffolds were designed using different material types and were modified to induce specific biological responses. Throughout the development of biomaterials for use in bone- tissue- engineering applications, regulatory agencies have evaluated products containing various biomaterials and have deemed several commercial products suitable for clinical use. BMP, bone morphogenetic protein; FDA, US Food and Drug Administration; RGD, arginine–glycine–aspartic acid.
3D, three- dimensional. The materials- design pathway begins with astrategic selection, which is followed by bthe optimization cycle. cFinally, the performance of materials is evaluated, which might direct the materials developer to return to the boptimization cycle
Paracrine is nothing but where they act on the neighbouring cells, the signal transfer
take place in the neighbouring cells.
In autocrine as it defines like it acts on itself the same cell.
Endocrine where it is transfer in the blood and tissues and it transported through the
blood and in the targeted site, it will enhance its property or elucidate its response.
(A) Two full-thickness critical bone defects (5 mm in diameter) were created in the rat parietal bone. Bone chips
are shown after trephination (arrows). (B) Implantation of PCL–TCP–Col1 scaffolds into the defects; inset, PCL–TCP scaffold
(5 mm diameter and 1 mm thick, 0–90
◦
lay-down pattern, 70% porosity) before treatment (left) and after lyophilization of
350 µg rat tail collagen 1 (right). (C, D) Micro-CT scanning of the skull defect showing the bone formation with and without
scaffold after 14 months of implantation. It can been seen in (D) that >90% of the original critical size defect is filled with bone.
(b) Implantation of a Mesenchymal stem cells (MSC)-loaded mPCL–CaP scaffold into the bone in a high load-bearing osteochondral
defect. (c) Implantation of a MSC-loaded mPCL–CaP scaffold in a pig spinal fusion model. The mechanical testing of mPCL-TCP
scaffolds show the high reproducibility of the manufacturing process (d) mPCL-TCP scaffolds seeded with BMSC’s were implanted
for 2 years in a critical size (15 mm) skulkl defects of New Zealand white rabbits. Analysis of the tissue engineered constructs (TEC)
showed bone formation throughout the entire scaffold and no fibrous tissue formation. MicroCT analysis revealed that 30% of the
mPCL-TCP is resorbed and replaced by bone
https://doi.org/10.1021/acsami.0c00275
Stem cells are usually extracted from the marrow of an adult bone and are, as a result, older. Their age affects the cells' ability to divide and produce more of the precious extracellular matrix.
Pluripotent stem cells, unlike adult mesenchymal cells that have a relatively short lifetime, they noted that these primitive cells can keep proliferating, thereby creating an unlimited supply of mesenchymal stem cells needed to make the extracellular matrix for bone grafts- can be made by genetically reprogramming donated adult cells.
Induced the pluripotent stem cells to make brand new mesenchymal stem cells, they were able to generate an extracellular matrix that was far more biologically active compared to that generated by mesenchymal cells obtained from adult bone
Implanted it at a site of bone defects-pluripotent stem-cell-derived matrix was five to six-fold more effective than the best FDA-approved graft stimulator.
Stem cells are recruited to the fracture site using a collagen matrix and then a bone-forming gene is directly delivered to the stem cells using an ultrasound pulse
his proposed therapy has the potential to generate rapid healing of segmental bone fractures and significantly decrease patient hospitalization, loss of working days and significant healthcare costs. In addition, this therapeutic intervention can be repeated several times when needed in order to deal with severe cases of bone loss.
Bonus BioGroup developed a unique method to grow three dimensional (3D), high-density, multi-cell bone grafts - BonoFillTM . These grafts are produced from patients' adipose (fat) tissue-derived cells, are designed to precisely fit the patients' deficient anatomical sites, and feature all ideal bone graft characteristics.