A recombinant matrix to improve autologous tissue grafts

Abstract The objective of this proposal is to validate a new regenerative tissue matrix which studies to date indicate may be possible of redefining the limits of autologous fat graftingThis objective is motivated by the currently limited surgical options available to themillion patients undergoing reconstructive plastic surgery each year to treat body disfigurement and dysfunctionA core component of many reconstructive procedures is filling a void with tissueand the use of autologous fat graftswith their innate biocompatibility and low procedural riskhas gained popularityDespite their increase in favorable outcomesobtaining consistent results has proved a significant challengeFor examplepatients undergoing post mastectomy breast reconstruction require an average of greater thansurgeries for procedural completion because of insufficient available volume of soft tissue or resorption due to insufficient vascularizationWhile attempts have been made to improve initial graft success rates by combining autologous tissue with synthetic polymers or patient derived decellularized tissuethese attempts have met with minimal success due to lack of intrinsic bioactivityhigh costor long processing timesRecombinant protein polymers are an unexplored but promising alternativewhereby mimics of naturally occurring extracellular matrix proteins can be recombinantly synthesized at high yield with molecular level control of their properties a precision far superior to synthetic polymersMotivated by this clear clinical needthis proposal seeks to optimize and test a recently developed innovative biomatrixFractomercomposed of an artificial recombinant protein designed to mimic native elastinThe Fractomer biomatrix is thermally responsiveallowing it to be injected as a liquidbut to rapidly phase transition in vivo to form a porousfractal network at body temperaturePreliminary studies have shown that this matrix is biocompatiblewith minimal inflammationno fibrous capsule formationexcellent tissue integrationand the rapid formation of the branching neovascular networks essential for tissue graft successOur central hypothesis is that the Fractomer matrix can stability integrate with and increase the effective volume of adipose tissuemaximizing graft success while reducing the required amount of autologous tissueThe following research strategy will be pursued in clinically relevant small animal models as a precursor to clinical implementationpurified fat prepared from human lipoaspirate at Duke University Hospital will be mixed with a Fractomer solution at different ratios in athymic miceand monitored for up tomonthsThe cellular composition and long term stability of the Fractomer matrix will be directly compared with both fat grafting and commercial hyaluronan gels with the goal of demonstrating permanent retention of higher graft volumesGraft weightvolumeand cellular composition as determined by a combination of computed tomography and histology will be used to evaluate graft successThe technology proposed here offers a basis for solving the fundamental issues associate with fat graft reliabilityandif successfulwould significantly reduce the necessity of secondary surgical procedures Project Narrative Autologous fat grafting is a valuable option to treat contour irregularities and volume deficits in the nearlymillion Americans undergoing reconstructive plastic surgery each yearThough preferred for their permanence and innate biocompatibilityfat grafts especially large volume grafts such as those used in post mastectomy patients routinely require multiple surgeries due to the insufficient available volume of harvested tissueTo alleviate the financial and health burden of multiple surgerieswe have developed a recombinant protein matrix which can be mixed with harvested tissue to expand volume and increase long term stability