Technologies for Natural‐Synthetic Polymer Hybrids: Synergistic Biointerface Engineering From Fabrication to Devices

ABSTRACT

This review summarizes natural and synthetic polymer hybrid materials for biointerface engineering. Natural polymers like chitosan, collagen, and hyaluronic acid (HA) provide biocompatibility and bioactivity but lack mechanical strength, whereas synthetic polymers such as polylactic acid, polycaprolactone, and polyethylene glycol offer tunable mechanical properties yet lack bioactive sites. Integrating these via physical blending, covalent functionalization, layer‐by‐layer assembly, block/graft copolymer design, in situ synthesis, and topographical patterning creates synergistic effects. These include balanced mechanical and biological performance, stimuli‐responsiveness to pH, temperature, enzymes, and magnetic fields, combined antifouling and targeting functions, immunomodulation, and multifunctional integration. Key applications encompass tissue engineering scaffolds, spatiotemporally controlled drug delivery, advanced biosensing, antimicrobial coatings, and organ‐on‐a‐chip platforms. Despite progress, challenges persist regarding natural polymer batch‐to‐batch variability, potential toxicity of synthetic degradation byproducts, long‐term stability, scalability of manufacturing, and clinical translation. Future research should prioritize multi‐responsive intelligent materials, AI‐driven design, green manufacturing, and interdisciplinary collaboration to standardize evaluation criteria and accelerate clinical use in regenerative medicine, personalized theranostics, and implantable electronics.