2.79J/3.96J/20.441J/HST522J Biomaterials-Tissue Interactions Reversible and Irreversible injuryInjury to adult ECM is irreversibleThe tissue triad in organsOrgans are made of tissues which heal differently from each other. The tissue triad in skin and nerves Conclusion2.79J/3.96J/20.441J/HST522J Biomaterials-Tissue InteractionsECM does not regenerate spontaneouslyORInjury to ECM is IrreversibleReversible and Irreversible injuryReversible injurySpontaneous regeneration of amputated limb in the newt occurs independently of severity of injuryGoss, 1992Figure removed due to copyright restrictions. See Figure 1.1 in [TORA].[TORA] = Yannas, I. V. Tissue and Organ Regeneration in Adults. New York, NY: Springer-Verlag, 2001. ISBN: 9780387952147. [Preview in Google Books]Irreversible injuryBurn victim suffering from severe contractionand scar formationTomasek et al., 2000Photo removed due to copyright restrictions.Injury to adult ECM is irreversibleSummary:1. After severe injury, and in contrast to the fetus, the adult heals most organs irreversibly (no regeneration). 2. Most organs are made up of three basic tissues (“tissue triad”): epithelia, basement membrane, and stroma.3. Epithelia and basement membrane are spontaneously regenerative; the stroma is not.4. Therefore, the central problem in biomaterials selection for organ replacement by regeneration is synthesis of the stroma.Text: Chaps. 1 and 2 of Tissue and Organ Regeneration in Adults, by I.V.Yannas, New York, Springer, 2001 (on reserve in MIT Libraries).The healed liver has the same mass, but a different shape (resected lobes are not regenerated), than the intact organFigure removed due to copyright restrictions. See Figure 1.2 in [TORA].scarred heart muscle(heart attack)scarred liver(cirrhosis)scarred cornea(infection)scarred kidneyImage removed due to copyright restrictions.See Figure 1.3 in [TORA].(infection)scarred heart valve(rheumatic fever)Pathology resulting from irreversibility of injury in various organsThe tissue triad in organs• epithelial tissue: 100% cellular, no ECM • basement membrane: 100% ECM , no cells • stroma: cells, ECM, blood vesselsOrgans are made of tissues which heal differently from each other. The tissue triad in skin and nerves100 µm───1 µm───Figure by MIT OpenCourseWare.Figure by MIT OpenCourseWare.Skin. Reversible InjuryFigure by MIT OpenCourseWare.Left: a controlled injury (e.g. stripping or blistering) which leaves the dermis intact.Right: the epidermis recovers completely at the defect site. Hair follicles are lined with epidermal tissue and also regenerate.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).Figure by MIT OpenCourseWare.Skin. Irreversible InjuryMildly crushed nerve heals spontaneously by regenerationPeripheral nerve. Reversible injuryWithin 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.Figure by MIT OpenCourseWare.Peripheral nerve. Irreversible injuryTransected nerve heals spontaneously by contraction and neuroma (neural scar) formation. No reconnection of stumps.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.Figure by MIT OpenCourseWare.intact nerve with myelinated (M) axon (A) and Schwann cell (S)spontaneously healed nerve (following transection) is filled with collagen fibers (scar) but has no myelinated axon or Schwann cellPeripheral Nerve. Irreversible InjuryFigure removed due to copyright restrictions. See Figure 2.5 in [TORA].injury modebasic blister configurationthrough dermis:irreversible healingthrough epidermis: reversible healingbetween epidermis and dermis:reversible healingIs the basement membrane regenerative?Yes!Figure removed due to copyright restrictions. See Figure 2.6 in [TORA].tissue triad in skinCartoon of “organism”shows that basement membrane (thick solid line) appears In almost all organsanatomyUse of tissue triad model with other organstissue triad in nerveFigures by MIT OpenCourseWare.Figure by MIT OpenCourseWare.Figure by MIT OpenCourseWare.Regenerative tissues. Reversible injury. No contraction.Nonregenerative tissues. Irrever-sible injury. Contraction+scar.SKIN epidermis dermisBMNERVE myelin endoneurial stromaBMSUMMARY SO FARConclusionThe central problem in organ regeneration is regeneration of the stroma. Once the stroma has been regenerated, epithelial tissues regenerate spontaneously and synthesize the basement membrane as wellMIT OpenCourseWarehttp://ocw.mit.edu 20.441J / 2.79J / 3.96J / HST.522J Biomaterials-Tissue InteractionsFall 2009For information about citing these materials or our Terms of Use, visit: