Xinqiao JiaDept. Materials Science and Engineering and Biomedical Engineering, University of Delaware
Our recent work is dedicated to the development of biomaterials-based strategies for the in vitro growth of replacement tissues and disease models. Using a high molecular weight hyaluronic acid (HA) carrying sulfhydryl groups (HA-SH) and a low molecular weight HA carrying reactive acrylates (HA-AC), we have created a cell-permissive hydrogel network that is conducive to the 3D assembly of salivary gland modules. In our system, the initial gelation occurred rapidly via thiol/acrylate Michael reaction to form a loose network for 3D encapsulation of dispersed human primary salivary gland cells. Owing to the significant access of thiols relative to the acrylate groups, disulfide bonds form slowly overtime to stabilize the matrix and to establish a redox-responsive microenvironment. These features, combined with susceptibility of the hydrogel matrix to hydrolytic degradation, contribute to the maintenance of the correct cell phenotype, foster intimate cell-cell communications and induce the assembly of organized, multicellular acinar spheroids. Modification of the above gel formulation and incorporation of growth factor depots and multivalent integrin binding motifs afforded a biologically relevant 3D culture system that recaptures essential features of prostate cancer microenvironment. Prostate cancer cells entrapped in the synthetic matrices formed distinct multicellular aggregates, expressed pro-angiogenic factors and exhibit inherent drug resistance. The PCa model was used successfully to test the efficacy of anti-cancer drugs, free or encapsulated in polymeric nanoparticles. Most recently, an ultrafast bioorthogonal reaction between s-tetrazine and trans-cyclooctones has been successfully applied to materials synthesis via diffusion controlled interfacial polymerization processes. Hydrogels with spatial patterns and polymer fibers with alternating molecular structure were successfully produced without having to rely on external triggers or polymer processing devices. The novel bioorthogonal platforms are being explored for the construction secretory salivary glands with a branched architecture, as well as advanced tumor models that recapitulate the PCa-nerve interface.
Hosted by Ying Liu