Bioinspired 3D-printing strategies for skeletal tissue regeneration: From natural architectures to clinical applications.

Skeletal tissues possess complicated structures and thereby their regeneration confronts considerable challenges. The final objective of skeletal tissue engineering is the development of efficient engineered substitutes in order to promote tissue regeneration. Numerous efforts have been made to develop functional biomimetic constructs with superior functions and characteristics to create advanced biomaterials for skeletal regeneration. One of the efficient approaches for designing bioinspired materials is mimicking the microstructure and architecture of natural living organisms and applying them in developing biomaterials with relevant functionality. Moreover, bioinspired complex structures which are developed by mimicking natural or synthetic architectures provide a crucial role in tissue engineering. Since the traditional approaches can not fulfill the demands to design intricate biomimetic materials, employing novel technologies may be satisfying. 3D bioprinting is a rapidly evolving technology which offers accurate multi-material and multi-scale manufacturing of biomimetic constructs for the patient-specific tissue regeneration. Numerous attempts such as mimicking the hierarchical structure and function of bone tissue, resembling the zonal architecture of cartilage tissue and imitating the microstructure and mechanical characteristics of natural osteochondral tissue, can suggest clinically desirable candidates for skeletal reconstruction. Here, 3D bioprinting technology for creating bioinspired constructs for use in skeletal tissue regeneration is discussed. We review various types of bioinspired constructs developed by mimicking the endogenous structure and function of skeletal tissues. Next, biomimetic constructs that are designed by imitating other natural and synthetic structures are discussed. Clinical trials utilizing 3D-printed constructs for skeletal tissue regeneration is discussed as the final part of the story. Different strategies such as mimicking strong adhesion to different surfaces, imitating the morphology of different architectures and resembling the hierarchical structure of natural and synthetic structures can expand the opportunity to develop realistic and effective constructs for clinical regeneration of skeletal tissue.