Department of Mechanical Engineering and Engineering Science, College of Engineering, UNC Charlotte
Engineering Human ECM Biomaterials
The extracellular matrix (ECM), composed primarily of collagen, elastin, laminin, fibronectin, proteoglycans, and other biomolecules, serves as the structural foundation of nearly all tissues and organs. It not only provides mechanical support but also mediates cell signaling through adhesion receptors and regulates the availability of soluble factors. Animal-derived biomaterials such as rat collagen I, Matrigel, Geltrex, and bovine fibrinogen are widely used in stem cell culture and tissue engineering due to their accessibility and low cost. In microvessel engineering specifically, rat tail collagen I and bovine fibrinogen are the most commonly employed materials. Although ECM components are often assumed to be conserved across species, notable differences exist between human and animal ECM that can significantly influence human cell behavior. Moreover, compositional disparities may introduce xenogeneic contaminants, raising concerns about immunogenicity and tumorigenicity. Human ECM-based biomaterials hold great promise for advancing tissue engineering; however, their limited availability and high cost remain major obstacles. To address this challenge, this project aims to develop hydrogel matrices that closely recapitulate human ECM by leveraging genetic engineering of iPSC-derived cells.
Engineering Functional Microcirculation
Microcirculation, consisting of arterioles, capillaries, and venules, is fundamental to vascular function—regulating blood flow (arterioles), enabling nutrient and oxygen exchange (capillaries), and facilitating immune surveillance (venules). Creating physiologically relevant microcirculation models is essential for engineering vascularized tissues, studying vascular pathologies, and advancing therapeutic screening. This project aims to engineer a functional microcirculation network composed of mature arterioles, capillaries, and venules. Aim 1 focuses on developing individual vessel models with appropriate supporting cells. Initial studies will utilize primary vascular cells and rat tail type I collagen, progressing to iPSC-derived vascular cells and human ECM-based biomaterials. Sacrificial hydrogel templates will guide mural cell seeding, basement membrane deposition, and endothelialization. Media composition and flow parameters—including shear stress, pressure, and pulsatility—will be optimized to ensure long-term vessel stability. Aim 2 seeks to integrate these vessel types into a unified microcirculation network on a single chip. Using 3D-printed sacrificial templates, we will fabricate interconnected vessels ranging from capillaries (~10 µm) to larger arterioles and venules (~200 µm), thereby recapitulating the hierarchical structure of native microcirculation.
Vascularized Skin Grafts
Skin grafts are generally divided into acellular and cellularized scaffolds. Acellular grafts—such as Integra, Biobrane, and Alloderm—are engineered or decellularized matrices that provide structural support for wound healing but lack the full function of native skin, often leading to scarring and poor sensory recovery. Cellularized grafts, including Episkin, Epicel, and Apligraf, contain cultured cells and are used to treat ulcers and burns, yet they still face major limitations.The main challenge with all current grafts is the absence of microvessels, which delays integration and increases the risk of graft failure, especially in severe burns and deep wounds. To address this, researchers have explored strategies such as co-culturing endothelial cells with fibroblasts or ECM to form small vessel networks, or using 3D-printed vascular templates. However, these approaches usually lack mature vessel features, perfusion capability, or true capillary-sized networks. This project aims to develop a vascularized skin graft with functional microvessels, enabling faster integration, improved survival, and better long-term outcomes.
