PURPOSE: Autologous fat grafting has emerged as a cornerstone of plastic surgery. Despite increasing applications in reconstructive and aesthetic surgery, fat grafting poses accessibility issues for patients with inadequate autologous tissue in addition to post-operative complications including fat displacement and necrosis. Currently marketed synthetic polymer or decellularized tissue injectables are inadequate to meet demand for a material able to augment autologous fat grafts due to a lack of intrinsic bioactivity, high cost, or long processing times. We report on the applications of an injectable biomatrix -Fractomer- and its ability to expand the effective volume of adipose tissue, adapt to different shapes, and reduce complications of fat grafting.
METHODS: We previously developed a recombinant protein matrix designed to mimic native elastin, modifying it to have temperature responsive phase behavior – turning from liquid to solid at body temperature.1 Rate of degradation and in vivo stability of the subcutaneously injected Fractomer wereTracked over 12 months in BL/6 mice using IVIS ® Spectrum in vivo imaging. In vivo biocompatibility was also assessed in Yucatan minipigs for 4 months. To test the combination of Fractomer and fat, human lipoaspirate was harvested, mixed with Fractomer, and subcutaneously injected into athymic mice. Resultant graft volume retention over 6 months was monitored and measured using micro-computed tomography. At the conclusion of all experiments, the injected grafts were excised, fixed, embedded in paraffin, sectioned, and stained to assess cell infiltration, vascularization, and foreign body response.
RESULTS: Fractomer is biocompatible with a degradation rate tunable (25-90% resorption range) with concentration. Histological analysis of Fractomer injections excised at 12 months revealed healthy integration with subcutaneous tissue, including significant vascularization, minimal fibrosis, and minimal inflammatory reaction. Similar results were obtained for Fractomer injections in minipigs, with a high level of vascularization, minimal fibrosis, and only quiescent macrophages present at 4 months. Compared to fat alone injections, Fat+Fractomer co-injections allowed 50% less fat to be used to obtain the same final graft volume at 6 months. On histological examination of the fat+Fractomer grafts, proliferation and remodeling of fat within the scaffold was seen along with evidence of vascularization, especially with areas of high Fractomer density. Importantly across all experiments no signs of cyst formation or necrosis were seen in the fat+Fractomer groups, whereas fat alone grafts demonstrated fat necrosis in 60% of injections.
CONCLUSION: Our studies to date demonstrate that the Fractomer biomatrix can integrate with and increase the effective volume of adipose tissue, maximizing graft success while reducing the required amount of autologous tissue needed for reconstruction. Fractomer achieves many coveted qualities of an ideal scaffold as it is angiogenic, biodegradable, and immune-compatible. Our findings demonstrate a viable option for reducing fat grafting complications and increasing accessibility for patients who were previously ineligible.
REFERENCE:
1. Roberts, S., Harmon, T. S., Schaal, J. L., Miao, V., Li, K. J., Hunt, A., Wen, Y., Oas, T. G., Collier, J. H., Pappu, R. V., & Chilkoti, A. (2018). Injectable tissue integrating networks from recombinant polypeptides with tunable order. Nature materials, 17(12), 1154 – 1163. https://doi.org/10.1038/s41563-018-0182-6