Biological function following radical photo-polymerization of biomedical polymers and surrounding tissues: Design considerations and cellular risk factors

Radical photo-cross-linking of polymers has been at the forefront in the development of biomedical applications to meet many of the biomaterial design criteria needed to address clinical and healthcare challenges, particularly in relation to regenerative and restorative medicine strategies, to treat damaged or diseased tissues and organs. Exciting new hybrid designs, elegantly expanding the range of properties and applications available to individual polymeric materials, are starting to offer detailed customization with complex and dynamic interactions similar to the events occurring within native tissue microenvironments in vivo. Yet the variety in success reported in the literature highlights the many unknown design criteria and parameters affecting functional restoration of damaged tissues and organs. The applied light curing units and radical initiating system, as well as underlying chemical reactions and resultant network structures, all require detailed consideration as means to modulate biological function while further being assessed as sources of toxicity. This is especially important when cells embedded in the polymeric material (or in surrounding tissues) are directly exposed to photo-irradiation. Ultimately, achieving successful clinical translation necessitates the chemical photo-polymerization platforms to be efficacious, safe, and customizable but also convenient for clinical use and cost-effective production. This review thus aims to summarize current and emerging toolkits to photo-polymerize biomedical polymers requiring the direct irradiation of cells and/or mammalian tissues and its associated impact on biological functionality. This specifically includes (1) in vitro photo-polymerization of cell-laden 3D-hydrogels for tissue engineering and regeneration medicine applications, (2) in vivo transdermal photo-polymerization of injectable hydrogels for cell/drug delivery, and (3) in vivo photo-polymerization of cell-free, injectable resin-based composites for load-bearing restorative surgery, all fast-growing and highly competitive fields of modern medicine. We herein summarize both design considerations and biological risk factors associated with selecting suitable light sources, photo-initiators, functional groups, chemical propagation, as well as how subsequent network properties can modulate biological function and ultimately clinical applicability. As more knowledge is continuously accumulated through materials science, matrix biology, and technology, this review provides recommendations for researchers to extend their chemical, biological, and structural characterizations to systematically enrich the paradigm of photo-polymerizable materials for biomedical applications to help ensure efficient and safe radical photo-processing.