Human Salivary Histatin-1-Functionalized Gelatin Methacrylate Hydrogels Promote the Regeneration of Cartilage and Subchondral Bone in Temporomandibular Joints

Abstract

The avascular structure and lack of regenerative cells make the repair of osteochondral defects in the temporomandibular joint (TMJ) highly challenging in the clinic. To provide a viable treatment option, we developed a methacrylated gelatin (Gel-MA) hydrogel functionalized with human salivary histatin-1 (Hst1). Gel-MA is highly biocompatible, biodegradable, and cost-effective. Hst1 is capable of activating a series of cell activities, such as adhesion, migration, differentiation, and angiogenesis. To evaluate the efficacy of Hst1/Gel-MA, critical-size osteochondral defects (3 mm in diameter and 3 mm in depth) of TMJ in New Zealand white rabbits were surgically created and randomly assigned to one of the three treatment groups: (1) control (no filling material); (2) Gel-MA hydrogel; (3) Hst1/Gel-MA hydrogel. Samples were retrieved 1, 2, and 4 weeks post-surgery and subjected to gross examination and a series of histomorphometric and immunological analyses. In comparison with the control and Gel-MA alone groups, Hst1/Gel-MA hydrogel was associated with significantly higher International Cartilage Repair Society score, modified O’Driscoll score, area percentages of newly formed bone, cartilage, collagen fiber, and glycosaminoglycan, and expression of collagen II and aggrecan. In conclusion, Hst1/Gel-MA hydrogels significantly enhance bone and cartilage regeneration, thus bearing promising application potential for repairing osteochondral defects.

Gelatin methacryloyl hydrogel with and without dental pulp stem cells for TMJ regeneration: An in vivo study in rabbits

“…26 The present study showed no difference in regenerative outcome when DPSCs were incorporated into the GelMA matrix, and neither produced significant cartilage regeneration in this rabbit model. This contrasts with the work of Shi et al 15 increased percentages of newly formed bone, cartilage, collagen fibre and glycosaminoglycan and expression of collagen II and aggrecan. Our study did not include an empty osteochondral defect group.…”

“…This supports the hypothesis that 4 weeks is insufficient for signs of cartilage repair to be manifested. These results contrast our previous mouse study 26 and recent animal studies, 15,16 where condylar cartilage and the subchondral bone layer regeneration were observed. Some potential factors may contribute to this apparent contradiction.…”

“…The present study showed no difference in regenerative outcome when DPSCs were incorporated into the GelMA matrix, and neither produced significant cartilage regeneration in this rabbit model. This contrasts with the work of Shi et al 15 . in a rabbit osteochondral model, showing that Hst1/GelMA hydrogel, in comparison with an empty control and GelMA alone groups demonstrated increased percentages of newly formed bone, cartilage, collagen fibre and glycosaminoglycan and expression of collagen II and aggrecan.…”

“…GelMA hydrogel can be photocured in situ and has good biocompatibility and tunable physicochemical properties for biomedical applications 13,14 . Shi et al 15 . reported that human salivary histatin‐1‐functionalized GelMA (Hst1/GelMA) hydrogels regenerated both the cartilage and subchondral bone in the TMJ condyle of rabbits.…”

“…GelMA hydrogel can be photocured in situ and has good biocompatibility and tunable physicochemical properties for biomedical applications. 13,14 Shi et al 15 reported that human salivary histatin-1-functionalized GelMA (Hst1/GelMA) hydrogels regenerated both the cartilage and subchondral bone in the TMJ condyle of rabbits. Yang et al 16 showed that rat bone marrow-derived mesenchymal stem cells (rBMSCs) loaded onto GelMA hydrogel microspheres promoted cartilage repair in the TMJ condyle of rats.…”