Lecture 3.2 - Regeneration and Repair PDF

Regeneration and repair: ◦In healing (or repair) of damaged tissue: ‣ Regeneration (functional repair) - is the growth of cells and tissues to replace lost structures, in which new growth completely restores portions of damaged tissue and recovers normal function (eventual...

Regeneration and repair: ◦In healing (or repair) of damaged tissue: ‣ Regeneration (functional repair) - is the growth of cells and tissues to replace lost structures, in which new growth completely restores portions of damaged tissue and recovers normal function (eventually no scar) ‣ Repair (fibrous repair) - a process when severely damaged or non-regenerate tissues are replaced by the connective tissue (scar) with loss of specialised function. Wound healing: wound and tissue injury: ◦Wound: ‣ A wound is an injury to the skin with/without underlying tissues/organs ‣ Caused by: Surgery A blow, cut, shear force Heat/cold Chemicals Disease, such as ulcers or carcinomas ◦Tissue injury: ‣ Any organ/tissue damages: ‣ Caused by: Traumatic events (car accidents) Ischemia/internal bleeding A sprain Aging Processes and timing of wound healing: Stages of the processes in wound healing: ◦There are 4 stages of wound healing: ‣ 1. Haemostasis - as vessels are open -> clot/scab to seal ‣ 2. Inflammation - as there has been tissue injury -> cytokines and phagocytosis ‣ 3. Proliferation - as structures have been injured/lost -> regrowth by stem cells -> reservation and repair ‣ 4. Remodelling -> functional regaining (scar disappearing and regeneration complete)  Cell types involved in healing (regeneration and scarring): ◦Inflammatory cells - neutrophils, macrophages, lymphocytes ‣ Phagocytosis of debris ‣ Production of chemical mediators ◦Endothelial (+ progenitor) cells proliferation ‣ Angiogenesis ◦Fibroblasts and myofibroblasts ‣ Produce collagen and contract ◦Parenchymal cells - skin epithelial cells (basal cells) ‣ Proliferate and restore skin structure Wound healing: granulation tissue: ◦Granulation tissue: ‣ Proliferation of the repair tissue ‣ Has a granular appearance and texture (red) ◦Consists of: ‣ Endothelial cells and capillaries ‣ Fibroblasts and myofibroblasts ‣ Type I collagen ‣ Chronic inflammatory cells ◦Functions: ‣ Fills the gap ‣ Angiogenesis (red) to supply oxygen, nutrients and cells ‣ Contracts and closes the wound ‣ Help lost tissue to restore Wound healing: fibroblasts/myofibroblasts: ◦Produce collagen (type I) ◦Contract and close the wound Wound healing: diseases related to collagen defect:  Wound healing: fibrous repair and scar: ◦Fibrous repair is scar formed by fibrovascular connective tissue that replaces lost tissue after an injury ‣ Occurs when extensive lost of tissue or/and local infection/persistent harmful agent ‣ Forming by overgrowth of granulation tissue into dense collagen fibres ‣ Associated with loss of function - flexibility, sweating, sensation ‣ Keloid-abnormal scar forming Complications of fibrous repair: Dynamic process of regeneration and fibrous repair: ◦Scarring is a natural part of the healing, skin scars are the normal and inevitable outcome of tissue repair ◦Scarring goes through the same 4 processes of the healing ◦Regeneration and fibrous scaring occur on varying combinations ◦Beneficial aspect - fibrous repair helps to close the wound, stop further damage Regeneration and repair in other organs and tissues: ◦Healing of bone fractures: ‣ Similar healing processes as at other tissues ‣ Some modification for special environment and structure of bone Haematoma - fills gap and surrounds injury. Inflammation occurs Granulation tissue forms - capillaries develop, cytokines activate osteoprogenitor cells Soft callus - at 1 week, fibrous tissue and cartilage Hard callus - after several weeks, initial woven bone forms - weaker and less organised than lamellar bone that can form quickly Lamellar bone - (normal bone structure) replaces woven bone Remodelling to mechanical stress, and bone not physically stressed is  resorted, bone structure is re-established, weeks-2 years Clinical classification - primary and secondary intention (union): ◦Healing by ‘primary intention’ ‣ Wound surfaces have been closed, with very little tissue loss and no infection (clean). Intact connective tissue scaffold (e.g. skin sharp cut, surgical incision, sutured wound) ‣ ——> Regeneration ◦Healing by ‘secondary intention’ ‣ A wound that is extensive and involves considerable tissue loss, and in which the edges cannot be brought together (e.g. ulcer, burn), infected wound ‣ ——> Fibrous repair ◦Tertiary intention healing - this type of wound healing is also known as “delayed” or “secondary closure” Summary: primary intention and secondary intention: Summary of healing: Factors influencing regeneration and repair:  Peripheral nerve regeneration/repair: Some consequences of healing - neuroma: ◦Traumatic neuroma is a benign growth (tumour) of nerve tissue (nerve fibres and myelin), that occurs in response to injury or surgery, when normal growth is interrupted ◦Symptoms - pain and abnormal sensation