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

Amy E. Anderson, Iwen Wu, Alexis J. Parrillo, David R. Maestas, Ian Graham, Ada J. Tam, Rachael M. Payne, Jeffrey Aston, Carisa M. Cooney, Patrick Byrne, Damon S. Cooney, Jennifer H. Elisseeff
2020 medRxiv   pre-print
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 trips to the operating room, and have highly variable outcomes. To address the clinical need for soft tissue reconstruction, we developed an off-the-shelf adipose matrix from allograft
more » ... n adipose 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 fat grafting materials. Biological activity was assessed using cell migration and stem cell adipogenesis assays. Characterization of the regenerative immunology properties in a murine muscle injury model revealed allograft and xenograft AAT induced pro-regenerative CD4+ T cells and macrophages with xenograft AAT attracting additional eosinophils secreting interleukin 4 (Il4). In immunocompromised mice, AAT injections retained similar tissue volumes as human fat grafts but did not have the cysts and calcifications that formed in the human fat graft implants. Combination of AAT with human adipose-derived stem cells (ASCs) resulted in lower implant volumes. However, tissue remodeling and new adipose development increased significantly with the addition of cells. Larger injected volumes of porcine-derived AAT demonstrated biocompatibility and greater volume retention when applied allogeneicly in Yorkshire cross pigs. Under a biologic IND application, AAT was implanted in healthy volunteers in abdominal tissue that was later removed (panniculectomy or abdominoplasty). The AAT implants were well tolerated and biocompatible in all eight human subjects. Analysis of 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.
doi:10.1101/2020.10.08.20206672 fatcat:iu62rvzamjh4hftuzi5xbwcxoq