Bone Tissue Biology & The Application of Synthetic Compounds for the Facilitation of Bone Tissue Healing Ryan T. Jones Western Michigan University May 2011
Introduction Bone has unique properties: Tensile Adaptive Achieved with cells that interact with both organic and inorganic extracellular matrix Environmental factors mediate intricate signaling pathways to control local cellular processes Homeostatic factors also mediate this system to ensure functionality for the body
Modeling, Remodeling, Damage & Repair Mechanisms/Processes in place to change/adapt bone structure: Modeling: addition/removal of new components without replacement Remodeling: coupled addition & removal of bone tissue Repair: restructuring/tissue generation after damage.
Bone Tissue Damage
Bone Tissue Remodeling
Homeostatic Fracture Repair
Synthetic Tissue Repair/Engineering On occasion, outside intervention may be required to facilitate the natural healing process Examples for need: Trauma Surgery Disease Immobilization to facilitate healing Physical support to avoid further damage Induce and support new tissue growth Expedite the healing process:
Tissue Repair Materials Materials developed: Bone Grafts Synthetic Cements Synthetic Ceramics Bioactive Glasses Glass Ionomers Synthetic Hydroxyapatite The application of metals & other materials Other/future therapies
Key Terms/Classifications of Materials Osteointegrative: Bonds/adheres well with existing tissue. Osteoinductive: Posses signaling factors that recruit bone progenitor cells. Osteoconductive: Readily serve as a medium for new bone tissue formation Osteogenetic: Posses inherient progenitor/stem cells with the ability to differentiate into bone cells
Bone Grafting Golden Standard of bone tissue healing facilitation Concepts found in Greek Mythology First documented use in 1668 A.D. Gained popularity during World War II 2 Types: Autogenious Grafting: transplant within same individual Allogenious Grafting: Transplant between individuals Transplant from cadaver
3 Days 1 Week 3 Weeks 4 Weeks
Autogenious Allogenious Bone Grafts Composition: Natural bone tissue Obtained from cadaver or donor Properties: Osteoinductive, Osteoconductive Osteogenetic* Osteointegrative*
Autogenious Bone Grafts Application: DBM Morselized Whole-segment Pros: Natural bone tissue More abundant supply Can undergo lab alteration Cons: Chances for rejection Chances for infection/disease transfer
Post-operation 10 months after operation
Acrylic Bone Cements Developed: Original use in early 20 th century. Originally used to facilitate fracture unions Now applied mainly in prosthetic implantation Properties: Variably osteointegrative Lacks: Osteoinductivity Osteoconductivity Osteogenicity
Acrylic Bone Cements Composition: methylacrylate Polymethylacrylate Application: Injection Paste/Putty Pros: Adheres to most materials and bone tissue Provides quick, tensile support
Acrylic Cements Complications Acrylic based cements can produce complications: Fibrous tissue encapsulation Local tissue damage from curing Toxicity of compounds used
Calcium-Sulfate Developed: Middle-east in the 10 th century to form splints Plaster of Paris Used as splints/bandages in early 20 th century In 1892, was successfully injected to treat tuberculous osteomyelitis Composition: Calcium-sulfate hydrate (Gypsum) (original) Calcium-sulfate hemi-hydrate + cellulose derivative Tissue engineering properties of: Provides Osteointegration & Osteoconduction Lacks: Osteoinduction & Osteogenicity
Calcium-Sulfate Application: Paste/putty or injection Pellets Pros: More absorbable than acrylic cements Easy to shape Provides immediate support Cons: Needs dry environments Current Use: Joints & small voids
Tricalcium-Phosphate Ceramics Developed: Originally used in 1920 as an injection Used today in solid or granular implantation Composition: Tricalcium-phosphate mixed in castor oil Properties: Osteointegration & Osteoconduction Lacks: Osteoinduction & Osteogenicity
Tricalcium-Phosphate Ceramics Application: Solid Blocks Granules Pros: Solid: Provides immediate structure Granular: Faster vascular invasion, absorbtion, and integration Cons: Solid: Not as easily absorbed Granular: Does not provide great support
Bioactive Glasses Developed: In response to Silicon-based material success First application in the 1970's Composition: Sodium and Calcium oxides Phosphorus pentoxide Silicon dioxide Properties: Osteointegration & Osteoconduction, Some Osteoinductive characteristics Lacks Osteogenicity
Bioactive Glasses Application: Solid & molded to desire Pros: Inherently alkaline to facilitate new bone growth Integrate well with existing tissue Can induce bone formation to some extent Cons: Minor chances for scar tissue formation Minor chances for rejection or toxicity Currently used extensively in Dentistry
Glass Ionomers Developed: First applications also in 1970's Originally intended for dental use Composition: Flurosilicate Calcium & Aluminium Properties: Osteointegration & Osteoconduction Some Osteoinductive characteristics Lacks Osteogenicity
Glass Ionomers Application: Semi-solid Paste/putty or Injection Pros: Easy to apply, especially for small voids Bio-compatible properties similar to bioactive glass Anti-bacterial Regulates gene expression? Cons: Possible problems with toxicity Lacks physical support
Synthetic Hydroxyapatite Developed: Synthetic preparation began in 1970's Directly for in vivo material application Composition: Prepared from natural apatite minerals Hydrated with precipitation or hydrolysis Properties: Osteointegrative Varying osteoconductivity Lacks osteoinductivity and osteogenicity (without supplemental materials)
Synthetic Hydroxyapatite Application: Ceramic or Non-ceramic Blocks or Granules Varying porosity Pros: Diversity of material characteristics Natural mineral found in bone Works well with other material types Cons: Depend upon material characteristics chosen
Stem Cell Therapy Provides properties of: Osteoinduction Osteogenicity Method: Bone marrow transplantation or aspiration Cultivation Combination with other materials or direct administration to area of need
Future Directions Development of new materials Development of new preparation methods Increases in stem-cell therapy research Bone morphogenetic protein (BMP's) research Gene-therapy?
Summary Many material options exist to provide individualized options in healing The continued use of materials will produce future discoveries of complications The recent addition of stem-cell therapies and other biomedical application have opened a new avenue of research for future therapies
Conclusion Biomedical research in preventative medicine will have the greatest impact on orthopedics New therapies will use existing mechanisms in place by body to ensure integrity of bone The bodies natural ability to heal is unmatched Individuals ultimately have control over their own bone health Easy, healthy lifestyle choices include: Balanced diet Avoiding risky activities Daily exercise