This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Keloids and hypertrophic scars are aberrant scarring processes characterized by excessive production of collagen and ground substance by fibroblasts in reaction to wounds. Current treatment options for keloids scars unsatisfactorily unreliable. These treatments include pressure and massage, intralesional triamcinolone injections, and surgical excision with or without laser therapy. These modalities are generally reported to be approximately 50% to 60% successful. The goals of this study were to design an investigational model enabling the study of potential treatments on fibroblasts derived from aberrant scars such as keloids and hypertrophic scars in a natural environment, over time. This would require non-destructive and minimally disruptive measurement techniques. We employed MPM to image artificial tissue engineered skin constructed with keloid-derived or normal dermal fibroblasts. Various types of wounds were simulated in the tissue-engineered skin constructs and MPM was used to monitor cell migration, scarring and healing. Specifically, we measured collagen production, which relies on intensity measurement and depth-dependent decay of second harmonic intensity in the skin constructs in the area of the wound. This project presents a wound-healing model designed to allow direct measurement of collagen production in a tissue-engineered skin construct. In future work this model will be used for the investigation of potential treatments for aberrant wounds consisting of excessive collagen deposition (keloids and hypertrophic scars). Potential treatment modalities that will be tested with this model include photodynamic therapy (PDT), leukotriene inhibitors, and physical environment modification (temperature, pressure, oxygen).
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