Fabrication of physical and chemical crosslinked hydrogels for bone tissue engineering

Bone tissue engineering has emerged as a significant research area that provides promising novel tools for the preparation of biomimetic hydrogels applied in bone-related diseases (e.g., bone defects, cartilage damage, osteoarthritis, etc.). Herein, thermal sensitive polymers (e.g., PNIPAAm, Soluplus, etc.) were introduced into main chains to fabricate biomimetic hydrogels with injectability and compatibility for those bone defect need minimally invasive surgery. Mineral ions (e.g., calcium, copper, zinc, and magnesium), as an indispensable role in maintaining the balance of the organism, were linked with polymer chains to form functional hydrogels for accelerating bone regeneration. In the chemically triggered hydrogel section, advanced hydrogels crosslinked by different molecular agents (e.g., genipin, dopamine, caffeic acid, and tannic acid) possess many advantages, including extensive selectivity, rapid gel-forming capacity and tunable mechanical property. Additionally, photo crosslinking hydrogel with rapid response and mild condition can be triggered by different photoinitiators (e.g., I2959, LAP, eosin Y, riboflavin, etc.) under specific wavelength of light. Moreover, enzyme triggered hydrogels were also utilized in the tissue regeneration due to its rapid gel-forming capacity and excellent biocompatibility. Particularly, some key factors that can determine the therapy effect for bone tissue engineering were also mentioned. Finally, brief summaries and remaining issues on how to properly design clinical-oriented hydrogels were provided in this review.
Graphical abstract Biomimetic hydrogels based on different crosslinking conditions, possess three-dimensional (3D) network with high aqueous content and functional properties, enabling their wide applications in bone tissue engineering. Recent advances in the design, preparation and application of light trigger hydrogels, thermal response hydrogels, small molecule crosslinking hydrogels, ionic crosslinking hydrogels and enzyme triggered hydrogels in the field of bone tissue engineering are reviewed.Image 1
Highlights • Diverse fabrication methods of advanced hydrogels were overviewed. • The process, advantages and drawbacks of advanced hydrogels were discussed. • Some key points in design of hydrogels for clinical use were summarized in this review. • The challenges, future directions and transformation potentials of hydrogels in bone tissue engineering were mentioned.