A recombinant matrix to improve autologous tissue grafts

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Project Summary The objective of this proposal is to further develop a new restorative tissue matrix which Phase I studies indicate is capable of expanding the utility of autologous fat grafting in breast reconstructive surgery. This objective is motivated by the need to improve the accessibility and safety of breast reconstruction for cancer patients. Breast implants dominate the field as they are easy to place and provide a defined shape. However, growing concerns over the long-term impact of implants with regards to capsular contracture, breast implant illness (BII) and breast implant associated anaplastic large cell lymphoma (BIA-ALCL) are driving many patients to seek other options. Tissue flap procedures effectively deliver large sections of fat to the defect; however, these procedures are complex, expensive, and not widely available to all patients. The long-term outcomes of successful tissue flaps are favorable but associated with significant investment in time, money, bodily scars, and effort. A third option is autologous fat, which can also be transferred as a graft using only liposuction and small injection cannulas as an outpatient procedure. Despite its potential, many surgeons feel limited in their capabilities when using fat grafts as: (1) harvesting fat with liposuction destroys its structural matrix, resulting in a shapeless slurry, and (2) many patients simply do not have enough fat to donate. To date, the technical and surgical barriers to using fat grafting for definitive breast reconstruction have not been solved. While attempts have been made to improve graft success rates by combining tissue with synthetic polymers or decellularized tissue, these attempts have shown minimal success due to a lack of intrinsic bioactivity, high cost, or long processing times. Recombinant protein polymers are an unexplored but promising alternative, whereby mimics of naturally occurring extracellular matrix proteins can be synthesized at high yield with molecular level control of their properties. Motivated by this clear clinical need, this proposal seeks to advance commercialization of a recently developed innovative biomatrix —Fractomer. Fractomers are artificial proteins designed to mimic soft tissue that can be co-injected with fat to expand volume, increase long-term stability, and improve fat shape by allowing tissue ingrowth and blood vessel formation. The Phase I program focused on Fractomer’s interaction with lipoaspirate to determine biomechanical and thermal response properties ideally suited to a tissue repair matrix. In vivo studies demonstrated Fractomer’s ability to promote cellular infiltration and vascularization associated with repair and remodeling, as opposed to scar formation and fibrosis. Finally, in a murine flank fat grafting model, Fractomer enabled the retention of form, localization, and structure of fat grafts up to three months. During Phase II we will continue commercial development of Fractomer by: 1) scaling manufacturing; 2) completing necessary biocompatibility and toxicity studies as required by the FDA for Investigational Device Exemption status prior to clinical testing; and 3) testing the material’s safety and efficacy in a porcine model of mammary fat pad repair.