1. Radostina Alexandrova, PhD
BONE IMPLANTS – OLD PROBLEMS AND NEW PERSPECTIVEES
Radostina Alexandrova, PhD
Institute of Experimental Morphology, Pathology AND Anthropology with Museum, Bulgarian Academy of Sciences

2. Collagen type I fibers (95%)
Bone tissue
Organic matrix
Collagen type I fibers (95%)
Proteoglicans and numerous non-collagenous proteins (5%)

3. structure of osseoum tissue

4. CELLS Cell type Origin Differentiation Function and phenotype
OSTEOBLASTS
(Four categories)
pluripotential mesenchymal
stem cells
Highly differentiated
!. Active osteoblasts - mononuclear cells with cuboidal shape; rich in alkaline phosphatase; synthesize and secrete collagen type I and glycoproteins (osteopontin, steocalcin), cytokines, and growth factors into a region of unmineralized matrix (osteoid) between the cell body and the mineralized matrix; produce calcium phosphate minerals extra- and intracellularly within vesicles;
2. Osteocytes – mature osteoblasts which have become trapped within the bone matrix and are responsible for its maintenance;
3. Bone-lining cells - found along the bone surfaces that are undergoing neither bone formation nor resorption, inactive cells that are believed to be precursors osteoblasts;
4. Inactive osteoblasts - elongated cells, undistinguishable morphologically from the bone-lining cells.
OSTEOCLASTS
hematopoietic stem cells (monocytes)
Polynuclear cells responsible for bone resorption (by acidification of bone mineral leading to its dissolution and by enzymatic degradation of demineralized extracellular bone matrix; important for growth and development
CHONDROCYTES
mesenchymal stem cells
Cells found in cartilage that produce and maintain the cartilaginous matrix
MESENCHYMAL STEM CELLS AND OSTEOPROGENITOR CELLS
Adult mesenchimal stem cells can be isolated from bone marrow, adipose tissues, or amniotic membrane; non differentiated with self-renewal capacity; multipotent cells able to repopulate all the appropriate differentiation lineages (osteoblastic, myoblastic, adipocytic, chondrocytic, endothelial, and neurogenic). For the osteogenic lineage, mesenchimal stem cells sustain a cascade of differentiation steps as described by the following sequence: Mesenchimal stem cell → immature osteoprogenitor → mature osteoprogenitor → preosteoblast → mature osteoblast → osteocyte or lining cell or apoptosis.
In bone marrow osteoprogenitor cells represent a very small percentage (e.g. < 0.005%) of nucleated cell types in healthy adult bone.
Osteoprogenitor stem cell differentiation is controlled by the “osteogenic mastergene” Cbfa1/Osf2 that intervenes in skeleton and tooth mineralization.

5. Hormones (parathyroid hormone (PTH) and 1α, 25(OH)2 vitamin D3)
Cytokines
Hormones (parathyroid hormone (PTH) and 1α, 25(OH)2 vitamin D3)
Growth factors (IGFs, PDGF, FGFs, VEGFs, tTGFs and bone morphogenic proteins (BMPs)

6. F U N C T I O N Involved in body protection, support and motion;
It is a protection and production site for specialized tissues (bone marrow, heart, lungs)
Supports structurally the mechanical action of soft tissues, like the construction of muscles or extension of lungs.
It is a mineral reservoir whereby endocrine system regulate the level of calcium and phosphate ions in the circulating body fluids

7. Mechanical properties

8. Congenitive disorders
Diseases
Trauma
Congenitive disorders
Cancer, ostoeporosis, Rheumatoid arthritis, etc
Fractura, Burning
BONE DEFFECTS

9. Techniques used to repair damaged bones
Autografts
Allografts
Limited availability
Foreign body reactions
Infections
Limited amount
Artificial materials

10. B I O M A T E R I A L S

11. DEFINITION OF BIOMATERIALS
A biomaterial can be defined as any material used to make devices to replace a part or a function of the body in a safe, reliable, economic, and physiologically acceptable manner. A variety of devices and materials is used in the treatment of disease or injury.

12. biocompatibility

13. Приложение на тъканното инженерство

14. BIOMATERIAL
SHORT CHARACTERISTIC
ADVANTAGES
DISADVAMTAGES
CERAMICS
Based mainly on hydroxyapatite, since this is the inorganic compound of bone
Able to form bone apatite-like material or carbonate hydroxyapatite on their surface, enhancing their osseointegration;
Able to bind and concentrate cytokines, as in the case of natural bone
Brittleness and slow degradation rates
METALS
Mainly stainless steel and titanium alloys (i.e. Ti-6Al-4V)
Excellent mechanical properties, which makes them the most widely applied implant material used in bone surgical repairs
The lack of tissue adherence and the low rate of degradation results either in a second surgery to remove the implant or in permanent implantation in the body with the related risks of toxicity due to accumulation of metal ions due to corrosion
NATURAL POLYMETS
Collagen and glycosaminoglycans
Silk-based biomaterials
Biocompatibility and biodegradability, since they compose the structural materials of tissues
Low mechanical strength and high rates of degradation (they are used in composites or in chemical modification by cross-linking. These changes make cause cytotoxic effects and reduce compatibility).
Biocompatibility, excellent mechanical properties, long-standing use of silk as sature material.
SYNTHETIC POLYMERS
The versatility of chemically synthesized polymers enables the fabrication of scaffolds with different features (forms, porosities and pore size, rates of degradation, mechanical properties) to match tissue specific applications
COMPOSITES
Each individual material has advantages for osteogenic applications, each also has drawbacks associated in certain properties (i.e. brittleness of ceramics) that can be overcome by combining different materials.

15. Orthopedic implants may fail owing to different reasons:
poor osseointegration at the tissue-implant interface
generation of wear debris
stress and imbalance between implant and surrounding tissues
infections
The average lifetime of the current bone biomaterials is less than 15 years

16. TISSUE ENGINEERING
STEM CELLS
SCAFFOLD

17. Osteogenesis occurs by seeding the scaffolds before implantation with cells that will establish new centers for bone formation, such as osteoblasts and mesenchymal cells that have the potential to commit to an osteoblastic lineage
Genetically transduced cells that express osteoinductive factors can also be used

18. Scaffolds for bone regeneration should meet certain criteria to serve this function:
Mechanical properties -
Biocompatibility and biodegradability
Osteoconductivity
Dlivery vehicles for cytokines such as BMPs, IGFs and TGFs –
similar to those of the bone repair site
at a rate commensurate with remodeling.
the phenomenon of new bone formation on the surfaces of biomaterial
that transform recruited precursor cells from the host into bone matrix producing cells, thus providing osteoinduction.

20. Cytokines
Growth factors
MSC protocol

21. 3D scaffold

22. Micrograph three-dimensional and inconsistency in pore sizes and surfaces of a cubic scaffold produced

24. 1.Activation: preosteoclasts are stimulated and differentiate under the influence of cytokines and growth factors into mature active osteoclasts
2. Resorption: osteoclasts digest mineral matrix (old bone)
3. Reversal: end of resorption
4. Formation: osteoblasts synthesize new bone matrix
5. Quiescence: osteoblasts become resting bone lining cells on the newly formed bone surface

25. The complexity of architecture and the variability of properties of bone tissue (e.g. porosity, pore size, mechanical properties, mineralization of mineral density, cell type and cytokine graduated features)
Differences in age, nutritional state, activity (mechanical loading and disease status of individuals
a major challenge in fabricating scaffolds and engineering bone tissues that will meet the needs of specific repair sites in specific patients

26. Poly(lactic-coglycolic acid scaffold

27. Acknowledgement: This study was supported by Grant DTK-02-70/2009, National Science Fund, Bulgaria

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