CHAPTER

1111Wound Healingand the Presenceof Biomaterials

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

11-2 Foreign Body Reaction Foreign body giant cells (FBGCs) --- multinucleated cells (monocytes/macrophage)

Relative composition of FBR (1)Surface properties of biomaterial

topography (roughness) / surface chemistry (2)Shape of the implants

high and low surface area/volume

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 (1)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

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

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

11-7 Techniques: In Vivo Assays for Inflammatory Response

Biological response via: (1)Interactions of biological molecules or cells with the implant (2)Interactions with soluble agents leached from the implant (3)Interactions with insoluble particulates (implant degradation) (4)Alterations in load or strain in the area around the implant

FDA: in vivo biocompatibility assessment biocompatibility / biocompatibility assessment

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 sizeb. Implant surface areac. Implant topographyd. # of implants per animal

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 (1)Histology / Immunohistochemistry (2)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