3D Bioprinting of Heterogeneous Constructs Providing Tissue‐Specific Microenvironment Based on Host–Guest Modulated Dynamic Hydrogel Bioink for Osteochondral Regeneration

Abstract

3D bioprinting is a promising strategy to develop heterogeneous constructs that mimic osteochondral tissue. However, conventional bioprinted hydrogels suffer from intrinsically weak mechanical strength, limited cell adaptability, and no sustained release of biochemical drugs, restraining their use as bioinks to emulate native osteochondral extra cellular matrix. Herein, a novel host-guest modulated dynamic hydrogel is developed for 3D bioprinting heterogeneous cell-laden constructs for osteochondral regeneration. Apart from gelatin methacryloyl (GelMA), this bioink consists of dopamine-functionalized GelMA and acrylate β-cyclodextrin and is crosslinked by host-guest interaction to develop the dynamic network for obtaining promoted cell adaptability, enhanced cell adhesion, reinforced mechanical strength, and tunable modulus. Moreover, based on the sustained drug release provided by the cavity of β-cyclodextrin, a heterogeneous construct is constructed by employing kartogenin (a chondrogenic factor) into the upper zone with lower Young's modulus and melatonin (an osteogenic factor) into the bottom zone with higher modulus to mimic the osteochondral microenvironment. With the favorable regeneration results in vitro and in vivo, a broad application of this bioink in 3D bioprinting for tissues engineering is expected.

Recent Advances of Natural Polysaccharide‐based Double‐network Hydrogels for Tissue Repair

“…[121] Recently, Dai et al developed a novel host-guest modulated dynamic DN hydrogel based on GelMA, dopamine-functionalized GelMA, and acrylated β-CD for 3D bioprinting heterogeneous cell-loaded structures that promote osteochondral regeneration (Figure 9C). [122] It had enhanced cell fitness, cell adhesion, mechanical strength. In addition, the host-guest interaction of the drug with β-CD further provided sustainable drug release for the modulation of signals that guide stem cell differentiation.…”

Recent development in multizonal scaffolds for osteochondral regeneration

“…The working principles and detailed mechanisms of these processes have been reported [ 289 , 300 , 304 , 305 ]. Thereinto, extrusion-based printing is considered the most prevalently implemented strategy to produce cell-free or cell-laden hydrogels and scaffolds for tissue regeneration and has been gaining momentum in recent years [ 121 , 289 , [305] , [306] , [307] , [308] , [309] , [310] ]. Fig.…”

Recent Advances in Host‐Guest Supramolecular Hydrogels for Biomedical Applications

“…In a very recent report, an intriguing host-guest modulated dynamic hydrogel with adjustable strength and good cell adaptability has been employed as bioink for 3D printing of biphasic cell-loaded constructions for osteochondral regeneration. [96] As shown in Figure 11a, the double-network hydrogel is derived from gelatin methacryloyl (GelMA), dopamine-functionalized gelatin methacryloyl (GelMA-DA), GelMA, and acrylate β-cyclo-Figure 10. Schematic illustration of the injectable and cell-infiltratable gelatin hydrogels as cell and drug carriers for treatment of SAON in rat model.…”