An immunologically active, adipose-derived extracellular matrix biomaterial for soft tissue reconstruction: concept to clinical trial

Soft tissue reconstruction remains an intractable clinical challenge as current surgical options and synthetic implants may produce inadequate outcomes. Soft tissue deficits may be surgically reconstructed using autologous adipose tissue, but these procedures can lead to donor site morbidity, require multiple procedures, and have highly variable outcomes. To address this clinical need, we developed an “off-the-shelf” adipose extracellular matrix (ECM) biomaterial from allograft human tissue (Acellular Adipose Tissue, AAT). We applied physical and chemical processing methods to remove lipids and create an injectable matrix that mimicked the properties of lipoaspirate. Biological activity was assessed using cell migration and adipogenesis assays. Characterization of regenerative immune properties in a murine muscle injury model revealed that allograft and xenograft AAT induced pro-regenerative CD4+ T cells and macrophages with xenograft AAT additionally attracting eosinophils secreting interleukin 4 (Il4). In immunocompromised mice, AAT injections retained similar volumes as human fat grafts but lacked cysts and calcifications seen in the fat grafts. The combination of AAT with human adipose-derived stem cells (ASCs) resulted in lower implant volumes. However, tissue remodeling and adipogenesis increased significantly in combination with ASCs. Larger injected volumes of porcine-derived AAT demonstrated biocompatibility and greater retention when applied allogeneicly in Yorkshire cross pigs. AAT was implanted in healthy volunteers in abdominal tissue that was later removed by elective procedures. AAT implants were well tolerated in all human subjects. Implants removed between 1 and 18 weeks demonstrated increasing cellular infiltration and immune populations, suggesting continued tissue remodeling and the potential for long-term tissue replacement.

Salvianolic Acid B Improves the Effect of Fat Grafts by Inhibiting the NF-kB Signalling Pathway in Macrophages

Background Autologous fat grafting (AFG), although an appealing approach to repair soft tissue defects, has various complications. Excessive inflammation at the transplant site is one of the main reasons for the poor effect of fat transplantation and occurrence of complications. Our previous study proved that Salvia miltiorrhiza can enhance fat graft survival. Salvianolic acid B (Sal-B) is the most abundant and bioactive water-soluble compound in Salvia miltiorrhiza and has anti-inflammatory effects on other diseases. Therefore, we hypothesized that salvianolic acid B could improve the effect of fat grafts by inhibiting inflammation. Methods In vivo, 0.2 ml of Coleman fat was transplanted into nude mice with salvianolic acid B. The grafts were evaluated by HE and IF at 2, 4 and 12 weeks posttransplantation and by micro-CT at 4 weeks posttransplantation. In vitro, the proliferative and anti-inflammatory activities of salvianolic acid B were analyzed in cultured RAW264.7 cells to detect the mechanism by which salvianolic acid B affects graft survival by inhibiting inflammation. Results In vivo, the degree of adipose tissue fibrosis and inflammatory cell infiltration in the salvianolic acid B treatment group was lower, and the infiltration of M1 macrophages in fat grafts was also less than that in the control group. In vitro, salvianolic acid B inhibited the proliferation and activation of inflammatory pathways in RAW264.7 cells. Conclusions This study demonstrates the use of salvianolic acid B as a possible treatment to improve the effect of fat transplantation.

Salvianolic acid-B improves fat graft survival by promoting proliferation and adipogenesis

Background Our previous study proved that Salvia miltiorrhiza could enhance fat graft survival by promoting adipogenesis. However, the effect of salvianolic acid B (Sal-B), the most abundant and bioactive water-soluble compound in Salvia miltiorrhiza, on fat graft survival has not yet been investigated. Objective This study aims to investigate whether salvianolic acid B could improve fat graft survival and promote preadipocyte differentiation. The underlying mechanism has also been studied. Methods In vivo, 0.2 ml of Coleman fat was transplanted into nude mice with salvianolic acid B. The grafts were evaluated by HE and IF at 2 and 4 weeks posttransplantation and by micro-CT at 4 weeks posttransplantation. In vitro, the adipogenesis and proliferative activities of salvianolic acid B were analyzed in cultured human adipose-derived stem cells (h-ADSCs) and 3T3-L1 cells to detect the mechanism by which salvianolic acid B affects graft survival. Results In vivo, the weights and volumes of the fat grafts in the Sal-B-treated groups were significantly higher than those of the fat grafts in the control group. In addition, higher fat integrity and more viable adipocytes were observed in the Sal-B-treated groups. In vitro, salvianolic acid B showed the ability to promote 3T3-L1 and h-ADSC proliferation and adipogenesis. Conclusions Our in vitro experiments demonstrated that salvianolic acid B can promote the proliferation of adipose stem cells and enhance the differentiation of adipose stem cells. Simultaneously, in vivo experiments showed that salvianolic acid B can improve the survival rate of fat transplantation. Therefore, our research shed light on the potential therapeutic usage of salvianolic acid B in improving the survival rate of fat transplantation.

Autologous Platelet-Rich Plasma Efficacy in the Field of Regenerative Medicine: Product and Quality Control

Platelet-rich plasma (PRP) has emerged as a significant regenerative therapy used alone or combined mainly with stem cells, autologous fat grafts, hyaluronic acid, and biomaterials in a variety of medical fields, especially in hair regrowth, wound healing, and sports and rehabilitation medicine. However, the results obtained with this biologic therapy are heterogeneous and conflicting. The observed disparities in the effectiveness of PRP therapies may be due to a lack of standardization in blood processing and preparation. This article is aimed at reviewing the main biological parameters that need to be documented for a thorough reporting of quantitative and qualitative characteristics of the PRP injected, to allow a comparison between the quality of samples and the clinically obtained results and advance the efforts towards treatment standardization.