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Biomimetic Nanofiber-hydrogel Materials And Autologous Adipocytes/Adipose-Derived Stem Cells Enable Durable Soft Tissue Restoration
Myan Bhoopalam, BA, MS, Ainsley Taylor, BS, Ya-Ching Hung, MD, Zhicheng Yao, BE, MSE, Jarvis Kong, BS, MSE, Hai-Quan Mao, PhD, Kevin Yang, PhD, Sashank K. Reddy, MD, PhD.
Johns Hopkins School of Medicine, Baltimore, MD, USA.

PURPOSE - Soft tissue losses from oncologic resection, trauma, aging, and congenital differences are a ubiquitous problem in clinical medicine. Lipotransfer of adipocytes and adipose-derived stem cells (ADSCs) has emerged as an important reconstructive strategy over the last two decades.1 Nonetheless, as currently practiced lipotransfer suffers from two major limitations (1) unpredictability of cell survival, and (2) limited long-term volume retention. Recently, we developed a nanofiber-hydrogel composite (NHC) that closely mimics the ultrastructure and macroscopic properties of adipose tissue while encouraging vascularization and soft tissue remodeling in vivo. Here, we explore the capacity of NHC to enhance survival, volume retention, and adipose tissue integrity of autologous transferred adipocytes and ADSCs.
METHODS - Nanofiber-hydrogel composite materials comprising of covalently linked hyaluronic acid and polycaprolactone nanofibers were prepared in fully-hydrated, beaded form. Autologous adipocytes and adipose derived stem cells were harvested from inguinal fat pads of Lewis rats, minced, and washed with PBS solution and passed through Luer lock syringes. The resulting adipose slurry -an autologous analog of human lipoaspirate-was mixed with NHC in varying ratios from 100% NHC to 100% adipose slurry (Figure). The mixtures were injected subcutaneously on the back of Lewis rats at a constant volume of 400cc per group. Volume retention and structural integrity were assessed by quantitative 3D MRI and histology.
RESULTS - Markedly improved volume retention was observed in the 100% NHC groups and the 50:50 NHC:fat groups with over 49% and over 40% of the original volume remaining at post-operation day (POD) 90, respectively. This is compared to 16.63% in the 100% fat group. Critically, the 50:50 NHC:fat group also had improved adipose tissue structure with discrete adipoctyes and fibrous septae evident as compared to the 100% fat group which had large oil droplets and vacuolar structures and a paucity of adipocytes and the 100% NHC group which showed a mixed inflammatory and fibrovascular infiltrate (Figure).
CONCLUSIONS - We demonstrated improved volume retention and structural integrity of transferred autologous adipocytes and ADSCs when combined in equal ratios with biomimetic nanomaterials. The use of an autologous lipotransfer model more closely mimics the clinical scenario than immunocompromised rodent models or allogeneic human fat transfer into immunocompetent models. Given the ongoing preclinical and clinical testing of NHC, we expect that this approach will powerfully complement traditional lipotransfer to enable more predictable and durable soft tissue restoration.
References - 1. James IB, Coleman SR, Rubin JP. Fat, Stem Cells, and Platelet-Rich Plasma. Clin Plast Surg. 2016 Jul;43(3):473-88. doi: 10.1016/j.cps.2016.03.017. PMID: 27363761.


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