Highly tunable bioactive fiber-reinforced hydrogel for guided bone regeneration

Abstract

One of the most damaging pathologies that affects the health of both soft and hard tissues around the tooth is periodontitis. Clinically, periodontal tissue destruction has been managed by an integrated approach involving elimination of injured tissues followed by regenerative strategies with bone substitutes and/or barrier membranes. Regrettably, a barrier membrane with predictable mechanical integrity and multifunctional therapeutic features has yet to be established. Herein, we report a fiber-reinforced hydrogel with unprecedented tunability in terms of mechanical competence and therapeutic features by integration of highly porous poly(ε-caprolactone) fibrous mesh(es) with well-controlled 3D architecture into bioactive amorphous magnesium phosphate-laden gelatin methacryloyl hydrogels. The presence of amorphous magnesium phosphate and PCL mesh in the hydrogel can control the mechanical properties and improve the osteogenic ability, opening a tremendous opportunity in guided bone regeneration (GBR). Results demonstrate that the presence of PCL meshes fabricated via melt electrowriting can delay hydrogel degradation preventing soft tissue invasion and providing the mechanical barrier to allow time for slower migrating progenitor cells to participate in bone regeneration due to their ability to differentiate into bone-forming cells. Altogether, our approach offers a platform technology for the development of the next-generation of GBR membranes with tunable mechanical and therapeutic properties to amplify bone regeneration in compromised sites. STATEMENT OF SIGNIFICANCE: In this study, we developed a fiber-reinforced hydrogel platform with unprecedented tunability in terms of mechanical competence and therapeutic features for guided bone regeneration. We successfully integrated highly porous poly(ε-caprolactone) [PCL] mesh(es) into amorphous magnesium phosphate-laden hydrogels. The stiffness of the engineered hydrogel was significantly enhanced, and this reinforcing effect could be modulated by altering the number of PCL meshes and tailoring the AMP concentration. Furthermore, the fiber-reinforced hydrogel showed favorable cellular responses, significantly higher rates of mineralization, upregulation of osteogenic-related genes and bone formation. In sum, these fiber-reinforced membranes in combination with therapeutic agent(s) embedded in the hydrogel offer a robust, highly tunable platform to amplify bone regeneration not only in periodontal defects, but also in other craniomaxillofacial sites.

Keywords: Bioprinting; Hydrogel; Magnesium phosphate; Melt electrowriting; Periodontal regeneration.