Principal Investigator: Stephen E. Feinberg, DDS, MS, PhD; Co-PI Mary-Ann Mycek, PhD
Organization: Regents of the University of Michigan
Our novel approach to reconstruct composite lip defects utilizes a prelaminated microvascular free flap based on latissimus dorsi muscle (LDM). The laminate is a tissue engineered medical product (TEMP) that is composed of autogenous oral and skin keratinocytes grown on an acellular dermal matrix. The oral stoma is maintained in the prelaminated flap utilizing a novel biocompatible obturator that is patent protected as is our technological approach with free and rotational flaps. This study uses a validated immunodeficient rat model for use in a preclinical animal study for data to be included in an IND submission to CBER/FDA for a first-in-human clinical trial. This preclinical animal study will focus on: (1) potential local toxicity of TEMP, (2) potential system toxicity of TEMP, and (3) vascularity and integration of TEMP with underlying muscle, maturation of the construct, and contractile capacity. We will conduct a controlled study with male immunodeficient rats in the following groups: control (no intervention), surgical control (isolation of LDM, placement of obturator) and test (isolation of LDM, placement of obturator and TEMP). Following euthanasia at 2 and 4 weeks, contractility will be assessed via video upon stimulating the thoracodorsal nerve. Construct maturation, TEMP vascularity and integration will be assessed by histology. Persistent zones of oral mucosa and skin epithelium and blood vessel formation will be assessed with immunohistochemistry.