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Scar formation and contraction around implantsA. Scar formation following traumaScar formation following trauma (cont.)B. Scar formation around “inert” implantC. Chronic scar formationD. Mechanism of scar formation. Scar forms secondary to contraction.Quantitative description of healing processesUnit cell processes of scar formationUnit cell processes of scar formation (Cont.)Developmental transition from scarless fetal to scarring (adult-type) fetal healingE. Templates prevent scar formation around implants by blocking contractionScar formation and contraction around implantsA. Scar formation following traumaB. Scar formation around “inert” implantC. Chronic scar formationD. Mechanism of scar formation. Scar forms secondary to contractionE. Templates prevent scar formation around implants by blocking contractionA. Scar formation following trauma1. Sources of trauma: energy sources.• mechanical: deep cut, laceration, surgery• thermal: fire, hot water.• electromagnetic: UV, electrical discharge• nuclear: radiation therapy.Skin: reversible injurySpontaneous regeneration of excised epidermisFigure by MIT OCW.Left: a controlled injury (e.g. stripping or blistering) which leaves the dermis intact. Right: the epidermis recovers completelyat the defect site. Hair follicles are lined with epidermal tissue and also regenerate.Skin: irreversible injurySpontaneous healing of skin excised to full thickness by contraction and scar formation. The dermis does not regenerate.Figure by MIT OCW.Left: Excision of the epidermis and dermis to its full thickness. Right: Wound edges contract and close, while scar tissue forms simultaneously in place of a physiological dermis. The epidermis that forms over the scar is thinner and lacks undulations (rete ridge).Peripheral nerve: reversible injuryMildly crushed nerve heals spontaneously by regenerationFigure by MIT OCW.Within the nerve fiber, axons and their myelin sheath are regenerative. Top: Following mild crushing injury, the axoplasm separates and the myelin sheath degenerates at the point of injury. However, the basement membrane stays intact.Bottom: The nerve fiber regenerates after a few weeks.Peripheral nerve: irreversible injuryTransected nerve heals spontaneously by contraction and neuroma (neural scar) formation. No reconnection of stumps.Figure by MIT OCW.Most supporting tissues (stroma) that surround nerve fibers are not regenerative. Thus, while nerve fibers can regenerate following a transection, the other tissues in the nerve trunk cannot regenerate. After transection, the nerve trunk stumps become neuromas - clumps of scarred tissue that close largely by contraction.Severity of injury determines its reversibilityFigure by MIT OCW.Scar formation following trauma (cont.)2. Morbidity of trauma, scar formation and contraction• on finger joint it prevents movement (“contracture”)• in peripheral nerves (neuroma) it prevents conduction of electric signals (paralysis)• in neck or face it creates serious problems of social acceptance• around suture points (e.g., following caesarian section)• surgical adhesions prevent normal function of intestines or lungs (e.g.,following heart surgery)Images removed due to copyright restrictions. Poster warning NFL football players not to tackle with the crown of their helmet ("Play Heads-Up!)Diagram describing angioplasty.B. Scar formation around “inert” implant1. Scarring following implantation of any nondegradableprosthesis (e.g., silicone, polyethylene)2. Constrictive scar tissue (fibrous capsule) around implant causes chronic pain and implant deformation3. Implantation of nonporous, biodegradable sheet under skin (subcutaneous) leads to encapsulation of implant by fibrotic tissue. No capsule formation around identical implant, except for being porous.4. Implants are often supported mechanically by contraction and scar formation around them.NORMAL IMPLANTImages removed due to copyright restrictions. Diagrams of human breast - normal and with implant.C. Chronic scar formation• Scar formation and contraction result from chronic trauma; or from acute or chronic inflammation caused by various agents• Scar takes different names depending on medical specialty• Examples: 1. Scarred heart valve due to incidence of rheumatic fever leads, e.g., to valve stenosis or to leakage.2. Necrosis (death) of myocardium (infarct)due to interruption of oxygen supply (clogged arteries) interferes with electrical conduction of heart muscle3. Obstruction of intestinal tract, due to chronic inflammation, leads to digestive problems (e.g., duodenal ulcer with gastric outlet obstruction)4. Fibrotic liver (cirrhosis) prevents liver functionscarred heart muscle(heart attack)scarred liver(cirrhosis)scarred cornea(infection)scarred kidney(infection)scarred heart valve(rheumatic fever)Figure 1.3 in [TORA]: Yannas, I. V. Tissue and Organ Regeneration in Adults. New York, NY: Springer, 2001. ISBN: 0387952144.Figure removed due to copyright restrictions.D. Mechanism of scar formation. Scar forms secondary to contraction.1. Macroscopic movement of tissue from periphery of wound toward center (contraction) with formation of scar near center.2. Contractile fibroblasts (myofibroblasts, MFB) may initiate contraction; they almost certainly propagate contraction.3. Collagen fibers in scar are highly oriented in the plane of the wound.4. Collagen fibers synthesized by MFB and extruded outside with fiber axis parallel to long cell axis. Fiber orientation is replica of MFB axis orientation during scar synthesis. 5. Collagen fiber orientation in scar is in the plane of the wound, suggesting that MFB are in a plane stress field during scar synthesis.6. Regeneration templates cancel out mechanical field, leading to randomization of MFB axes and fiber synthesis in random orientation.Burn patienthas closed severe skin wounds in neck partly by contractionand partly by scarFinal state of healing of full-thickness skin wound in the human.Photo removed due to copyright restrictions.Tomasek et al., 2000Spontaneous contraction and scar formation in burn victimPhoto removed due to copyright restrictions.Contracting skin wound.Guinea pig model. Adipose tissue layerunderneathis greatlydeformedby contracting wound.Natural light. Conventional histologicalview. Stained with H&E.S, scar. D, dermis.A, adipose tissue.Viewed in polarized lightstage. Collagen fibers light up.Photos removed due to copyright restrictions.Edge of


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MIT 2 782J - Study Notes

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