Gradient Biomolecular Immobilization of 3D Structured Poly‐ɛ‐caprolactone Biomaterials toward Functional Engineered Tissue

Abstract Additive manufacturing (AM) enables the tailored production of precision fibrous scaffolds toward various engineered tissue models. Moreover, by functionalizing scaffolds in either a uniform or gradient pattern of biomolecules, different target tissues can be fabricated in vitro to capture key characteristics of in vivo cellular microenvironments. However, current engineered tissue models lack the appropriate cellular cues that are needed to deterministically direct cell behavior. Specifically, tunable and reproducible scaffold‐guided stimuli are identified herein as the missing link between biomaterial structure and cellular behavior. Therefore, the bottleneck of precision control is addressed here over the immobilization of patterned biomolecular stimuli with either uniform or gradient distribution over the AM‐enabled 3D biomaterial model as a function of different growth factors exposure variables, protocols, and various scaffold architectural design parameters. The produced study outcomes herein will improve the directing and guiding of biological cell attachment and growth direction in the context of scaffold‐guided stimuli techniques. Therefore, unprecedented control is presented here over 3D structured biomaterial gradient functionalization and immobilization of biomolecules toward biomimetic tissue architectures.