Strategy

Introduction

            There has been a lot of research done in the area of scarless wound healing.  A few selected studies are discussed on the literature page.  What follows below is a hypothetical strategy to reduce scar formation in dermal wounds.  This strategy was conceived by considering the results of the previously mentioned studies, among others.  It is not suggested that this strategy is the best approach to achieve scarless wound healing, nor even is a measure of its effectiveness hypothesized.  Rather, it serves as a demonstration of how an effective strategy for scarless healing could be found by integrating the findings of many different studies and bases of knowledge.
           Also, by presenting additional information in this manner, it is hoped that the overall considerations of the scarless wound healing problem can be more completely appreciated.  Hopefully, this could lead to other promising strategies leading to improved dermal wound healing.

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A Proposed Strategy

            Based on the findings of these studies and similar studies not mentioned, an approach to encourage scarless healing of cutaneous wounds is proposed.  It is the goal to integrate several approaches that have shown promise in reducing scar formation to treat cutaneous wounds.  It is now helpful to lucidly present the systems we wish to merge to create this novel wound treatment.  The base of the healing salve would be very similar to antibiotic ointments currently on the market.  It is proposed to apply a specialized wound dressing to help mimic the subcutaneous environment.  Added to the salve base would be factors to accomplish two specific goals: TGF-β1 suppression and the relaxation of tension in the wound.
            An existing triple antibiotic ointment could be used as the base for the salve.  The medium is a white petrolatum with cocoa butter, cottonseed oil, olive oil, sodium pyruvate, vitamin E.  The active ingredients are bacitracin zinc 400 units, Neomycin 3.5 mg and Polymyxin B sulfate 5,000 units. [9]. Neomycin and polymyxin are effective in killing gram-negative bacteria, while bacitracin targets gram-positive bacteria; hence, this 'triple antibiotic' ointment covers for a wide range of bacteria which may infect wounds. [10] Topical antibacterial ointments such as these not only help prevent infections, but also significantly speed up the healing of the wound.  The petrolatum keeps the wound moist, preventing scab formation.  Studies have shown that wounds heal significantly faster if prevented from scabbing.  Also, due to the results of Adzick’s work with fetal healing, we wish to mimic the subcutaneous environment.  A wound dressing designed to seal the wound from the external environment (and air) is suggested.  This would help mimic the subcutaneous environment and would be more similar to the amniotic environment, both of which may help induce favorable healing as seen in the results of Adzick’s study.
            Adzick, Szpaderska, Siebert, Krummell, and Chipey and Simon have all linked TGF-β to increased fibroblast differentiation to myofibroblasts, which is thought to eventually lead to increased scarring.  It will be attempted to suppress TGF-β expression to consequently reduce the differentiation of fibroblasts to myofibroblasts.  This will be done with an antisense oligonucleotide (ASO) technology, as previously described. [11] Human TGF-β1 ASOs contained in the ointment will be delivered to the cells in proximity of the wound via liposome encapsulation .
            Chipey and Simon found that decreased tension in the extraceullular matrix led to decreased fibroblast differentiation to myofibroblasts.  Accordingly, we will attempt to lower the tissue tension of the wound to achieve the same affect.  Cytochalasin D, which blocks the polymerization and elongation of actin filaments, will be included in the ointment.  Brown et al. studied the effect of CD on tissue tension in a 3D fibroblast-collagen lattice model.  In the study, human dermal fibroblasts were used.  After adding CD to the model, the tension decreased significantly, from 1.3 mN to 0.4 mN.  The CD acts to stop cell generated tension, thus in their experiment, 0.9 mN of force was cell generated tension, while the other 0.4 mN was due to residual stress in the collagen matrix. [12] Accordingly, including CD in the salve should greatly reduce the tissue tension of the wound and this should lower fibroblast differentiation to myofibroblasts.

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Conclusion

           The final salve and bandage system together will hopefully encourage scarless wound healing in cutaneous wounds.  The main idea of this approach of decreasing scar formation is to attempt to limit the genesis of myofibroblasts in the wound.  This approach is novel in that it uses a multi-faceted strategy borrowing from several dissimilar previously described strategies.  It is hoped that the effectiveness of each individual strategy could be combined to create a collective strategy that is more effective than each alone.
           The main concerns with the strategy laid out above is that the wound healing process is not fully understood.  In fact, none of the individual processes discussed are completely understood, nor is the complete function of the proteins discussed.  Previous studies related to wound healing have found adverse consequences when manipulating the wound healing process such as inflammation and delayed scab loss. [13] Thus, although while the healing process will hopefully react favorably to our approach, the opposite is also possible.  For instance, decreasing the number of myofibroblasts at the wound site should also lower the amount of wound contraction occurring.  Hopefully the negative consequences of this could be overcome by providing antibiotics and sealing the wound from the environment.  Also, if this approach worked and scarring was reduced/eliminated, then the principal negative consequence of the larger wound size would be negated.

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