Massachusetts Institute of Technology Harvard Medical School Brigham and Women’s Hospital VA Boston Healthcare System 2.79J/3.96J/BE.441/HST522J UNIT CELL PROCESSES ASSOCIATED WITH WOUND HEALING I.V. Yannas, Ph.D. and M. Spector, Ph.D. WOUND HEALING Roots of the Tissue Response Injury Inflammation (Vascularized tissue) Healing Process Regeneration* Repair (Scar) CT: bone CT: cartilage Ep: epidermis Nerve Muscle: smooth Muscle: cardiac, skel. 4 Tissue Categories Connective Tissue Epithelium Nerve Muscle *spontaneous Resolution Slight No Healing Nonvascularized tissue RESPONSE TO IMPLANTS: WOUND HEALING Injury Vascular Response Inflammation Tissue of Labile Tissue of and Stable Cells Permanent Cells Framework Framework Scar Intact Destroyed Regeneration Scar RESPONSE TO IMPLANTS: WOUND HEALING Surgical Implantation Vascular Response Clotting Phagocytosis Neovascularization New Collagen Synthesis Tissue of Labile and Stable Cells Tissue of Permanent Cells Framework Framework Scarring Intact Destroyed (fibrous encapsulation; synovium) Regen. Scarring Chronic Inflammation (incorp. (fibrous encapsulation; of implant) synovium) Chronic Inflammation Acute Inflammation Granulation Tissue Implant Movement Inc. time UNIT CELL PROCESSES Cell + Matrix Product + Regulator Regulator Mitosis Synthesis Migration Contraction Endocytosis Exocytosis UCP Connective Tissue Epithelia Muscle Nerve ECM Adhesion Protein Collagen Biomaterial Integrin UNIT CELL PROCESSES VASCULAR RESPONSE Endothelial Cell + Basal Lamina Leakage + Reg. Contraction UNIT CELL PROCESSES VASCULAR RESPONSE Endothelial Cell + Basal Lamina Leakage + Reg. Contraction Platelet + serum Reg. Exocytosis Basophil + serum Reg. Exocytosis Mast Cell + ECM Reg. Exocytosis Seratonin Histamine PAF Seratonin (circulation) (circulation) (tissue) UNIT CELL PROCESSES VASCULAR RESPONSE Endothelial Cell + Basal Lamina Leakage + Reg. Contraction Smooth Muscle + Basal Lamina Vasoconstrict. Contraction Platelet + serum Reg. Exocytosis Basophil + serum Reg. Exocytosis Mast Cell + ECM Reg. Exocytosis Histamine Cell Seratonin Histamine PAF Seratonin UNIT CELL PROCESSES CLOTTING Platelet + Collagen Coaguation factors Exocytosis Fibrin polymerization UNIT CELL PROCESSES CLOTTING Platelet + Collagen Coaguation factors Exocytosis Basophil + serum Reg. Exocytosis Mast Cell + ECM Reg. Exocytosis Fibrin polymerization PAF PAF (In Circulation) (In Tissue) UNIT CELL PROCESSES PHAGOCYTOSIS Macrophage + Part.* Sol. Part + Reg. Endocytosis * Cell debris and degraded ECM UNIT CELL PROCESSES PHAGOCYTOSIS Macrophage + Part.* Sol. Part + Reg. Endocytosis Fibroblast + ECM + Reg. Endothelial Cell + ECM + Reg. * Cell debris and degraded ECM UNIT CELL PROCESSES NEOVASCULARIZATION Synthesis: enzymes Endothelial Cell + Basal Lamina + Reg. Migration Endothelial Cell + ECM + Reg. Endothelial Cell + ECM + Reg. Mitosis UNIT CELL PROCESSES NEW COLLAGEN SYNTHESIS Fibroblast + ECM + Reg. Migration Fibroblast + ECM + Reg. Mitosis Synthesis Fibroblast + ECM + Reg. Fibroblast* + ECM + Reg. Contraction *Myofibroblast UNIT CELL PROCESSES NEW COLLAGEN SYNTHESIS Fibroblast + ECM + Reg. Migration Fibroblast + ECM + Reg. Mitosis Synthesis Fibroblast + ECM + Reg. UNIT CELL PROCESSES Fibroblast + Collagen Contracture + Reg. TGF-β1 Contraction