RESUMO
Stem cells have been introduced as a promising therapy for acute and chronic wounds, including burn injuries. The effects of stem cell-based wound therapies are believed to result from the secreted bioactive molecules produced by stem cells. Therefore, treatments using stem cell-derived conditioned medium (CM) (referred to as secretome) have been proposed as an alternative option for wound care. However, safety and regulatory concerns exist due to the uncharacterized biochemical content and variability across different batches of CM samples. This study presents an alternative treatment strategy to mitigate these concerns by using fully characterized recombinant proteins identified by the CM analysis to promote pro-regenerative healing. This study analyzed the secretome profile generated from human placental stem cell (hPSC) cultures and identified nine predominantly expressed proteins (ANG-1, FGF-7, Follistatin, HGF, IL-6, Insulin, TGFß-1, uPAR, and VEGF) that are known to contribute to wound healing and angiogenesis. These proteins, referred to as s (CMFs), were used in combination to test the effects on human dermal fibroblasts (HDFs). Our results showed that CMF treatment increased the HDF growth and accelerated cell migration and wound closure, similar to stem cell and CM treatments. In addition, the CMF treatment promoted angiogenesis by enhancing new vessel formation. These findings suggest that the defined CMF identified by the CM proteomic analysis could be an effective therapeutic solution for wound healing applications. Our strategy eliminates the regulatory concerns present with stem cell-derived secretomes and could be developed as an off-the-shelf product for immediate wound care and accelerating healing.
RESUMO
BACKGROUND: Alloplastic implants have been used clinically to treat congenital abnormalities and traumatic injuries. However, these implants are often associated with complications, including inflammation, infection, erosion, and dislodgment. To minimize these complications, the authors have developed a system in which tissue-engineered cartilage serves as a shell that entirely covers the implant. This system is designed to improve the structural and functional stability between the implant and recipient tissue. METHODS: Chondrocytes isolated from rabbit ear cartilage were expanded in vitro. The cells were mixed with fibrin hydrogel for spray-coating a human ear-shaped implant. The surface of the implant was modified using an oxidizing solution to provide hydrophilic characteristic; thus, the cell-fibrin suspension readily adhered onto the surface of the implants. The engineered cartilage-covered implants were implanted into the dorsal subcutaneous space of athymic mice. Histologic and gross examinations of the implants were performed at 2, 4, 8, and 12 weeks after implantation. RESULTS: None of the engineered cartilage-covered implants showed evidence of skin necrosis, implant exposure, or extrusion (n = 10). However, the control implants developed extensive necrosis following implantation (n = 10). In the experimental group, histologic evaluations showed the formation of neocartilage covering the implants. The presence of sulfated glycosaminoglycans was evident in the engineered cartilage tissue. CONCLUSIONS: These results demonstrate that engineered cartilage tissues can be used as a biological cover for an alloplastic implant. This system may improve the structural and functional interactions between the implant and the recipient's tissues and thus enhance the outcome of total auricular reconstruction.
