Porcine Bi-layered Living Cellular Construct Promotes Healing in Diabetic Porcine Model

Introduction: Diabetic patients are prone to developing chronic wounds due to numerous underlying causes, some of those including being vulnerable to infections, dysregulated growth factor levels, and altered MMP expression. These chronic wounds often have persistent levels of inflammation and stalled re-epithelialization, which may lead to complications and ultimately, amputation. Treatment of chronic wounds involves sharp debridement often followed by a skin substitute to support healing. Bi-layered Living Cellular Construct (BLCC*) has been engineered to mimic human skin and consists of fibroblasts, keratinocytes, and a bovine collagen matrix. A comparable porcine-derived BLCC (pBLCC) was developed to study how BLCCs could promote healing in a full-thickness, diabetic porcine model without the complexity resultant from a xenogeneic response.Methods:32 to 36 months prior to study, Yucatan miniature pigs were chemically induced to become diabetic using alloxan. Full-thickness wounds (4cmx4cm) (Nf6/pig) were generated on the backs of pigs (Nf5); wounds were not treated (control, Nf10) or treated with either a single pBLCC treatment (Nf10) or multiple pBLCC treatments (Nf10). Healing was assessed by planimetry and histological assessment.Results: A single application of pBLCC resulted in greater wound healing by day 17, while four applications of pBLCC resulted in statistically greater healing on days 10, 13, and 17 compared to control wounds. Wound closure of pBLCC-treated wounds was primarily driven by re-epithelialization rather than contraction or granulation. Computational modeling mirrored the in vivo findings, with multiple pBLCC applications resulting in 90% closure rates 4 days quicker than a single application of pBLCC and up to two weeks faster than untreated control.Discussion: pBLCCs had comparable structure to human BLCCs and promoted increased rates of wound closure between days 10 and 21 after even a single application. Regardless of whether wounds received a single or multiple applications of pBLCC, statistically more rapid re-epithelialization of wounds was observed compared to untreated controls in this diabetic porcine wound model. These findings build upon the existing literature of how BLCCs may improve wound healing.References: