ALBERT

Description: Polymeric scaffolds such as hydrogels can be engineered to restore, maintain, or improve impaired tissues and organs. However, most hydrogels require surgical implantation that can cause several complications such as infection and damage to adjacent tissues. Therefore, developing minimally invasive strategies is of critical importance for these purposes. Herein, we developed several injectable cryogels made out of hyaluronic acid and gelatin for tissue-engineering applications. The physicochemical properties of hyaluronic acid combined with the intrinsic cell-adhesion properties of gelatin can provide suitable physical support for the attachment, survival, and spreading of cells. The physical characteristics of pure gelatin cryogels, such as mechanics and injectability, were enhanced once copolymerized with hyaluronic acid. Reciprocally, the adhesion of 3T3 cells cultured in hyaluronic acid cryogels was enhanced when formulated with gelatin. Furthermore, cryogels had a minimal effect on bone marrow dendritic cell activation, suggesting their cytocompatibility. Finally, in vitro studies revealed that copolymerizing gelatin with hyaluronic acid did not significantly alter their respective intrinsic biological properties. These findings suggest that hyaluronic acid-co-gelatin cryogels combined the favorable inherent properties of each biopolymer, providing a mechanically robust, cell-responsive, macroporous, and injectable platform for tissue-engineering applications.

Description: Porous three-dimensional hydrogel scaffolds have an exquisite ability to promote tissue repair. However, because of their high water content and invasive nature during surgical implantation, hydrogels are at an increased risk of bacterial infection. Recently, we have developed elastic biomimetic cryogels, an advanced type of polymeric hydrogel, that are syringe-deliverable through hypodermic needles. These needle-injectable cryogels have unique properties, including large and interconnected pores, mechanical robustness, and shape-memory. Like hydrogels, cryogels are also susceptible to colonization by microbial pathogens. To that end, our minimally invasive cryogels have been engineered to address this challenge. Specifically, we hybridized the cryogels with calcium peroxide microparticles to controllably produce bactericidal hydrogen peroxide. Our novel microcomposite cryogels exhibit antimicrobial properties and inhibit antibiotic-resistant bacteria (MRSA and Pseudomonas aeruginosa), the most common cause of biomaterial implant failure in modern medicine. Moreover, the cryogels showed negligible cytotoxicity toward murine fibroblasts and prevented activation of primary bone marrow-derived dendritic cells ex vivo. Finally, in vivo data suggested tissue integration, biodegradation, and minimal host inflammatory responses when the antimicrobial cryogels, even when purposely contaminated with bacteria, were subcutaneously injected in mice. Collectively, these needle-injectable microcomposite cryogels show great promise for biomedical applications, especially in tissue engineering and regenerative medicine.