Abstract
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.
Highlights
Soft tissue damage can occur due to traumatic injury, congenital and acquired medical conditions, infection, aging, or ablative surgical procedures such as tumor resection
Synthetic implants can be used to treat some types of soft tissue defects such as those used for breast reconstruction following a mastectomy
Surgical approaches to treat soft tissue defects may utilize autologous tissue harvested from the patient to provide a living implant for reconstruction as an alternative to synthetic implants
Summary
Soft tissue damage can occur due to traumatic injury, congenital and acquired medical conditions, infection, aging, or ablative surgical procedures such as tumor resection. Surgical approaches to treat soft tissue defects may utilize autologous tissue harvested from the patient to provide a living implant for reconstruction as an alternative to synthetic implants. Poor viability of transplanted adipose tissue can lead to necrosis, calcifications, and cyst formation[2,3,4,5]. The unpredictability of these procedures can result in costly secondary surgeries and are limited by the volume of autologous tissue available in each patient, as well as comorbidities related to tissue harvest and scarring at the donor site[6]. There is a significant need for a biomaterial solution that could provide the benefits of autologous adipose tissue with the ease of use and delivery of synthetic implants
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