Research
The Kwee Laboratory develops innovative approaches to enhance the efficacy of tissue engineering therapies, in the context of lymphatic, nerve, vascular, and skeletal muscle regeneration. We are specifically interested integrating concepts of immunoengineering, drug delivery, biomaterials, and cell manufacturing to enhance these therapies in two broad areas:
In situ tissue engineering with immunomodulatory biomaterials: It is becoming increasingly appreciated that the immune system plays a critical role in tissue regeneration. However, impaired or prolonged inflammation can lead to adverse tissue responses, such as fibrosis and necrosis. We design cell and drug delivery biomaterials that can recruit host immune cells and modulate them to promote muscle regeneration. Our designed biomaterials control the number and type of innate and adaptive immune cells (i.e. macrophages and T-cells) at sites of injury and disease to induce pro-regenerative inflammatory microenvironments (Fig. 1).
Fig. 1. Schematic illustration of immunomodulatory biomaterials for regenerating vascular, nerve, and skeletal muscle tissue. (Figure made with BioRender)
Representative Publications in this area:
1. Kwee BJ, Mooney DJ. Manipulating the intersection of angiogenesis and inflammation. Annals of biomedical engineering. 2015, 43:628-640. [Link]
2. Kwee BJ, et al. CD4 T-cells Regulate Angiogenesis and Myogenesis. Biomaterials. 2018, 178:109-121. [Link]
3. Raimondo TM, Li H, Kwee BJ, Kinsley S, Budina E, Anderson EM, Doherty EJ, Talbot SG, Mooney DJ. Combined delivery of VEGF and IGF-1 promotes functional innervation in mice and improves muscle transplantation in rabbits. Biomaterials. 2019, 216:119-246. [Link]
4. Kwee BJ, et al. Treating ischemia via recruitment of antigen-specific T cells. Science Advances. 2019, 5(7):eaav6313. [Link]
Cell manufacturing applied to tissue engineering: The clinical success of cell therapies is limited by cellular functional heterogeneity, where cells from different donors or subpopulations within a donor exhibit varying potency. Our work focuses on reducing this heterogeneity with fluorescence-activated cell sorting (FACS) to identify cell subpopulations of varying therapeutic potency in biomaterials. We focus on sorting these cells by integrin/cadherin expression and evaluating how these cell subpopulations function and/or form tissues in biomaterial scaffolds. We are applying this cell manufacturing approach to endothelial cells and muscle cells combined with biomaterials to engineer vascularized muscle tissues (Fig. 2).
Fig 2. Schematic illustration of manufacturing cells for engineered vascularized skeletal muscle tissue. (Figure made with BioRender)
Representative Publications in this area:
1. Kwee BJ, Sung KE. Engineering microenvironments for cell therapy product manufacturing. Experimental Biology and Medicine. 2021, 246: 1845–1856. [Link]
2. Kwee BJ, et al.. Functional heterogeneity of IFN-γ-licensed mesenchymal stromal cell immunosuppressive capacity on biomaterials. PNAS. 2021, 118 (35): e2105972118. [Link]