Engineered stimuli-responsive smart grafts for bone regeneration

Complex tissue regeneration through biomaterial-based strategies has witnessed a substantial structural transformation to facilitate the attachment and migration of host cells. Smart biomaterials offer exceptional features by rearranging themselves into diverse conformations upon exposure to physical (e.g., magnetic, temperature, electric field, and light), chemical (e.g., pH and ionic strength), or biological (e.g., enzymes) stimuli. By engineering conventional biomaterials into threedimensional smart porous constructs (i.e., grafts) with novel sensory materials through a range of chemical and physical processing routes, it is possible to mimic the diverse mechanical, biological, and physiochemical nature of bone tissue. The resulting smart grafts can efficiently deliver the appropriate signals and guide the stem cells to promote tissue regeneration. In addition, they regulate the release of various bioactive agents in response to external and internal stimuli while combatting infections at the wound sites. This review discusses numerous strategies to engineer synthetic polymers to yield stimuli-responsive smart grafts suitable for bone tissue engineering. Various additives have also been included, ranging from nanoparticles to biologically active agents responsible for the graft's smart function. Furthermore, the review highlights recent trends and developments, contemporary challenges, and future perspectives of smart stimuli responsive grafts concerning bone tissue engineering.