Wound Healing Process

In man and domestic animals, scarring left after a trauma, surgery, burn or sports injury is an important medical problem, often resulting in altered aesthetics, loss of function, restriction of tissue movement and/or growth and adverse psychological effects.

Modern treatments are empirical, troublesome and unpredictable: there are no prescription medicines for the avoidance or treatment of dermal scarring. Skin wounds on early mammalian embryos cure flawlessly with no scars whereas wounds in adult mammals scar.

Scientists are investigating the cellular and molecular differences between scar-free healing in embryonic and adult wounds. Important differences include the inflammatory response, which in embryonic wounds consists of fewer numbers of less differentiated inflammatory cells. This, together with augmented levels of morphogenetic molecules involved in skin growth and morphogenesis, implies that the growth factor profile in a healing embryonic wound is very different from that in an adult wound.

These experiments result in scar-free wound healing in adults. Such experiments have allowed the recognition of therapeutic targets; an appropriate treatment clearly improves or completely avoids scarring during adult wound healing in experimental animals. Some of these new medications have successfully completed safety tests and others. This has allowed them to enter human clinical trials with approval from the appropriate regulatory authorities. Based on encouraging results attained from these experiments lead medications have now entered human patient-based trials e.g. in skin graft donor sites.

The theory is that evolutionary pressures have been exerted on medium sized, widespread, dirty wounds with considerable tissue destruction e.g. bites, bruises and contusions. Modern wounds (e.g. resulting from trauma or surgery) caused by sharp instruments and healing in a clean or aseptic environment with close tissue apposition are recent situations, not previously encountered in Nature and to which the evolutionary selected wound healing reactions are somewhat useless. It has been demonstrated that both repair with scarring and regeneration can occur within the same animal, including man, and of course within the same tissue, thereby suggesting that they share similar procedures and regulators.

Consequently, by slightly altering the ratio of growth factors present in adult wound healing, we can induce adult wounds to heal flawlessly with no scars, with accelerated healing and with no adverse effects, e.g. on wound strength or wound infection rates. This implies that scarring may no longer be an inevitable consequence of modem injury or surgery and that a fully new pharmaceutical concept to the avoidance of human scarring is now possible. Not only skin suffers from scarring; they can appear in many other tissues as well.

Thus scar-improving treatments could have extensive benefits and avoid complications in several tissues, e.g. prevention of blindness after scarring due to eye damage, support of neuronal reconnections in the central and peripheral nervous system by the elimination of glial scarring, restitution of normal gut and reproductive function by preventing strictures and adhesions after damage to the gastrointestinal or reproductive tracts, and recovery of locomotor function by preventing scarring in tendons and ligaments.

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