Examination of endothelial cell‐induced epidermal regeneration in a mice‐based chimney wound model

Abstract

As wound contraction in the cutaneous layer occurs rapidly in mice, mechanical means are typically used to deliberately expose the wound to properly investigate healing by secondary intention. Previously, silicon rings and splinting models were attempted to analyze histological recovery but prevention of surrounding epidermal cell migration and subsequent closure was minimal. Here, we developed an ideal chimney wound model to evaluate epidermal regeneration in murine under hESC-EC transplantation through histological analysis encompassing the three phases of regeneration: migration, proliferation, and remodeling. Human embryonic stem cell derived endothelial cells (hESC-EC) were transplanted due to possessing a well-known therapeutic effect in angiogenesis which also enhances epidermal repair to depict the process of regeneration. Following a standard 1 mm biopsy punch, a chimney manufactured by modifying a 1.7 mL microtube was simply inserted into the excisional wound to complete the modeling process. Under this model, the excisional wound remained fully exposed for 14 days and even after 4 weeks, only a thin transparent layer of epidermal tissue covered the wound site. This approach is able to more accurately depict epidermal repair in relation to histology while also being a user-friendly and cost-effective way to mimic human recovery in rodents and evaluate epithelial repair induced by a form of therapy.

Reconstituting Human Cutaneous Regeneration in Humanized Mice under Endothelial Cell Therapy

“…An excisional wound was made dorsal surface at the middle site using a standard 8-mm biopsy punch (Acuderm Inc, Fort Lauderdale, FL). A chimney was completely inserted into the excisional wound as described previously (Seo et al, 2016). Subsequently, PBS, CB-EPC, or hPSC-EC (3 Â 10 5 cells) were injected into the chimney by combining Growth Factor-Reduced BD Matrigel to reduce cell migration within the transplanted region.…”

Therapeutic Efficacy of Artificial Skin Produced by 3D Bioprinting

“…However, the mechanism of skin regeneration in rodents differs from that of humans. The chimney wound model can simulate the human wound-healing process in mice; it involves the implantation of a structure called a chimney to prevent wound contraction [ 18 , 21 ]. The conventional chimney wound model uses a nonbiocompatible material known as a microtube.…”

“…For the wound-healing study, we used a chimney model mimicking the human wound-healing process [ 18 , 21 ]. This chimney model was established in Balb/c nude mice (Orient Bio Inc., Gyeonggi-do, Korea), as described in a previous study [ 18 ].…”

“…For the wound-healing study, we used a chimney model mimicking the human wound-healing process [ 18 , 21 ]. This chimney model was established in Balb/c nude mice (Orient Bio Inc., Gyeonggi-do, Korea), as described in a previous study [ 18 ]. Briefly, mice were anesthetized with an intraperitoneal injection of 40 μL of a solution containing ketamine (10 mg/kg; Ketamine, Yuhan Co., Seoul, Korea) and xylazine (40 mg/kg; Rompun®, Bayer, Leverkusen, Germany).…”

“…Skin defect models evaluate skin regeneration by an artificial wound such as an incision, excision, or burn. A newly proposed mouse chimney wound model could be a suitable animal experimental model for examining the recovery of skin wounds in that it is similar to that of a human, so in this study, we assessed the therapeutic effects of 3D-printed skin substitutes in an environment mimicking the human wound-healing process [ 18 ].…”