Development of Organic/Inorganic Compatible and Sustainably Bioactive Composites for Effective Bone Regeneration

Abstract

In this paper, we demonstrate a strategy of covalently bonding bioactive molecules onto inorganic hydroxyapatite (HAp) to improve the compatibility between organic and inorganic components and endow the bone composites with sustainable bioactivity. Bone morphogenetic protein-2 (BMP-2) peptide covalently immobilized nano-hydroxyapatite (nHAp-BMP-2) is developed to preserve the bioactivity and slow the release of the BMP-2 peptide. Then nHAp-BMP-2 was further incorporated into an ultraviolet-curable mixture of gelatin methacrylamide (GelMA) and four-armed PEG methacrylamide (four-armed PEGMA) to form a Gel/(nHAp-BMP-2) composite. The hydrogen bonding between gelatin and BMP-2 on nHAp-BMP-2 enhanced the compatibility between inorganic and organic components. The Gel/(nHAp-BMP-2) composite exhibited superior biocompatibility caused by gelatin and nHAp-BMP-2, except in a two-dimensional cell culture, the hydrogel was also capable of a three-dimensional cell culture. In addition, the introduction of nHAp-BMP-2 had a positive influence on bone marrow mesenchymal stem cell proliferation, differentiation, and the subsequent calcification on the composite. After treatment of a rat calvarial defect model for 12 weeks, the Gel/(nHAp-BMP-2) group showed the largest new bone volume and the highest ratio of new bone (50.54 ± 13.51 mm and 64.38 ± 17.22%, respectively) compared to those of the other groups. These results demonstrate that this way of controlling BMP-2 release is effective and the Gel/(nHAp-BMP-2) composite has great potential in bone regeneration therapy.

Bioprinted Injectable Hierarchically Porous Gelatin Methacryloyl Hydrogel Constructs with Shape‐Memory Properties

“…Other possible strategies to prolong the degradation time could be achieved by incorporating other biocompatible components. [23] The higher mechanical property could be further accessed by incorporating bioinorganic materials (such as hydroxyapatite [24] ) as needed.…”

Synthesis and Properties of Gelatin Methacryloyl (GelMA) Hydrogels and Their Recent Applications in Load-Bearing Tissue

“…3D scaffold of GelMA hydrogels can guide the formation of a desired tissue due to their attachment sites and signaling cues. A variety of applications of GelMA hydrogels had been reported in tissue engineering, such as bones [44,45,46,47,48,49,50,51,52,53,54,55,56,57], endochondral bone [58,59], skin [60,61,62,63,64,65], myocardium [66], cardiac tissues [67,68,69,70,71,72], cartilage [42,73,74,75,76,77,78,79,80,81], vascular networks [82,83,84,85,86,87,88,89], skeletal muscle [90,91,92,93], cornea [94,95], interface [96] and so on. Ovsianikov A et al [44] prepared 3D CAD scaffolds for tissue engineering applications using two-photon polymerization (2PP).…”

In vivo study of polyurethane and tannin-modified hydroxyapatite composites for calvarial regeneration

“…Elaborately designed artificial bone grafts should be biocompatible and biodegradable as well as osteoconductive, osteoinductive and angiogenesis promoting, providing temporary and gradually regressive substitutes in the bone defect sites, and actively promote bone regeneration in the degradation process. 2,5,[9][10][11][12][13][14][15][16][17][18] However, the fabrication of ideal bone grafts are still challenging.…”