The interaction of biomaterials with biological systems is a complex process, that is triggered in response to implants and wounds. It is essential to understand the phases of wound healing response, particularly the interactions of immune cells such as macrophages and fibroblasts, with the local extracellular matrix which can influence implant acceptance or the restoration of the damaged wound site. Materials properties such as compressive modulus, surface geometry, functionalization, and topology can be tuned to modulate the inflammatory and fibrotic responses to wounds and implants. Naturally derived materials, such as alginate, are widely used biomaterials owing to their biocompatibility and the diverse crosslinking strategies that can be used for fabrication. Soft alginate gels can be synthesized after methacrylation to be relatively stable under physiological conditions, while retaining pH sensitivity, which can be useful in the treatment of chronic wounds. Studying the collagen response to NIH/3T3 fibroblasts encapsulated in these soft hydrogels can develop wound healing strategies to promote faster wound healing. The transition of collagen organization from aligned to isotropic states in the dually crosslinked stiffer methacrylated alginate (ALGMA) hydrogels shows promise towards the development of topical gels for wound care. Modifying the surface properties using arginine-like derivatives is effective in modulating the fibroblast response to implanted glass beads in SKH1-E mice. Collagen response to modified glass beads using SHG microscopy was evaluated using several factors such as collagen amount, secretion of collagen III, and organization of collagen. The albizziin modification showed both isotropic collagen organization as well similar collagen type III as unwounded skin. Furthermore, statistical analysis uncovered correlations between SHG derived parameters and the materials properties of the chemical modifiers. Collagen type III was correlated with the surface tension of the modifier, and an empirical equation was derived relating materials parameters with the observed collagen measurements. The effectiveness of diverse wound care strategies on shallow and deep wounds on porcine subjects was conducted using SHG microscopy. Treatment duration, as well as scaffold preparation were instrumental in reducing a scarring response and accelerating wound closure rates. By combining the understanding of wound healing in diverse tissue environments, with environmentally responsive wound dressings, it is possible to improve the quality of life for millions of patients across the world.