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CHAPTER 11

Wound Healing and the Presence of Biomaterials. CHAPTER 11. 11-1 Introduction: Formation of Granulation Tissue 24 hrs: macrophages and inflammatory cells --- chemoattractants -- migration of fibroblasts and vascular endothelial cells. 3-5 days:

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CHAPTER 11

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  1. Wound Healing and the Presence of Biomaterials CHAPTER 11 • 11-1 Introduction: Formation of Granulation Tissue • 24 hrs: macrophages and inflammatory cells --- chemoattractants • -- migration of fibroblasts and vascular endothelial cells 3-5 days: (1) beginning of granulation tissue formation neovascularization and angiogenesis (2) proliferation of fibroblasts connective tissues and myofibroblasts

  2. 11-2 Foreign Body Reaction • Foreign body giant cells (FBGCs) --- multinucleated cells (monocytes/macrophage) • Relative composition of FBR • Surface properties of biomaterial • topography (roughness) / surface chemistry • Shape of the implants • high and low surface area/volume

  3. 11-3 Fibrous Encapsulation • Granulation tissue maturation (large blood vessels & collagen fiber alignment) • Long-term capsule formation (4 weeks post-implantation) • (1) Degree of original injury during implantation • (2) Amount of subsequent cell death • (3) Location of implant site • (4) Degradation time of implant • Thickness of the capsule • Amount & chemical composition of • small particulates produced • (2) Mechanical factors at implant site • (3) Shape of implant • (4) Electrical currents • 11-4 Chronic Inflammation • Between acute and full development of granulation tissue • Granulomas • Epitheloid cells

  4. 11-5 Four Types of Resolution Extrusion / Resolution / Integration / Encapsulation - Failure or success 11-6 Repair vs Regeneration: Wound Healing in Skin - Tissue repair with scar tissue - Tissue regeneration with identical tissue 11.6.1 Skin Repair Skin = internal dermal layer + outer epidermal layer Injury --- blood clotting --- fibrin network --- acute inflammation --- influx of fibroblasts into ECM --- beginning of granulation tissue --- Remodeling and scar formation collagen III turnover (1) collagen I (2) GAG ratio 변화 collagen accumulation

  5. 11.6.2 Skin Regeneration Erosions: small skin wounds within the epidermal layer Re-epithelialization Defect --- cell flattening --- cell migration --- cell proliferation migration edge in contact with other epithelial cells --- cuboid morphology and re-attach to ECM --- proliferation and matrix production --- restoring the original thickness of tissue

  6. 11-7 Techniques: In Vivo Assays for Inflammatory Response • Biological response via: • Interactions of biological molecules or cells with the implant • Interactions with soluble agents leached from the implant • Interactions with insoluble particulates (implant degradation) • Alterations in load or strain in the area around the implant • FDA: in vivo biocompatibility assessment • biocompatibility / biocompatibility assessment

  7. 11.7.1 Considerations in development of animal models (1) Choice of animals: small vs. large animals (2) Choice of implant site: vascularized area / surrounding cell’s ability (3) Length of study acute / subacute / subchronic / chronic toxicity (4) Biomaterial consideration: dose and administration shape Biocompatibility test to screen novel materials to assess the inflammatory response to the material a. Implant weight and/or bulk size b. Implant surface area c. Implant topography d. # of implants per animal

  8. Direct implantation / Extracts of the material / Cage implant model • (5) Inclusion of proper controls • a. intact contra-lateral tissue • b. an unfilled surgical implant site • c. material and device controls • 11-7-2 Methods of Assessment • Histology / Immunohistochemistry • Electron microscopy • TEM and SEM • (3) Biochemical assays • colorimetry assay for bioactive molecules • immuno-based assay • (4) Mechanical testing • the implant + surrounding tissue • ---- tensile, bending, push-out tests • remodeling around the implant • integration of the implant

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