Wound Healing: Past, Present and Future; Is It Time for a Treatment Paradigm Shift? Editorial Summary ‘Normal’ evolutionary wound healing processes that have been in place over time have been altered. This articles discusses an overview of the mechanisms that have caused deviation from the normal evoluionary processes. Theories are explored about the high incidence of chronic or hard-to-heal wounds.
Introduction
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Dr Kenneth Burhop Life Sciences Advisor and Consultant San Diego CA, United States
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n the surface, wound healing as designed or evolved by nature is a rather straight forward process and the same basic principles apply to the past, present and future. The response to injury in a foetus and neonatal mammals involves very little inflammation, is primarily regenerative in nature, and leads to very little fibrosis and complete healing. In contrast, the response to injury in adults first involves significant inflammation with very little regeneration, followed by fibrosis. In animals, these same basic principles have remained consistent over time. Regardless of the tissue type, the regenerative process adheres to similar principles: first, recruitment and migration and attachment of cells, followed by cellular proliferation and differentiation, which then leads to tissue deposition, and ultimately, tissue remodeling. In nature when an animal becomes injured, the wound healing process focuses on rapid recovery as aesthetics are of no importance. Animals really don’t care what they look like, as long they are able to stay alive and defend themselves. Assuming the injury is non-critical and that there is no major infection (which is a key assumption), animals are generally successful in healing their own wounds without much/ any intervention. What happens if we now move to man? If we look at the very distant past, one can assume that these same basic principles seen in animals applied to adult humans, as survival was paramount. However, if we step forward to the present time, and see the high incidence of chronic wounds that don’t heal, we have to ask the question ‘what happened’? Why is it that today we have
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such a high incidence of chronic wounds that don’t heal and why is there such a significant impairment of normal wound healing? To answer this, I believe we have to now consider all of the complicating factors that man has introduced into and on top of the ‘natural processes’ over time. That is, the incidence of concomitant factors today is significantly higher. For example, and just to name a few, animals don’t smoke, the incidence of diabetes and hypertension is lower in animals; animals do not typically have vascular disease, animals do not take dozens of medications; animals don’t care about the aesthetic outcomes of healing (speed is of the utmost importance), they are not dependent on Centers for Medicare & Medicaid Services (CMS) or insurance carriers to approve and pay for their treatment, and they don’t have to worry about inpatient or outpatient perspective payment systems and physician fee schedules. As a result of these and many other factors, in humans today the ‘normal’ processes that have been in place over time have been altered and wound healing has become much more complicated. If we then think about tissue engineering of new products to address this more complicated situation, while the goals of tissue engineering remain relatively the same and simple on the surface (i.e., prevent infection, prevent fibrosis and promote regeneration and incorporate tissue, signals and cells), the solution set is now multifactorial. While the three main factors that must be considered, i.e., tissue, signals and cells, remain the same, the problem is significantly compounded.