Mesoporous Hydroxyapatite Nanoparticles Mediate the Release and Bioactivity of BMP-2 for Enhanced Bone Regeneration

Abstract

Efficient delivery of bone morphogenetic protein-2 (BMP-2) with desirable bioactivity is still a great challenge in the field of bone regeneration. In this study, a silk fibroin/chitosan scaffold incorporated with BMP-2-loaded mesoporous hydroxyapatite nanoparticles (mHANPs) was prepared (SCH-L). BMP-2 was preloaded onto mHANPs with a high surface area before mixing with a silk fibroin/chitosan composite. Bare (without BMP-2) silk fibroin/chitosan/mHANP (SCH) scaffolds and SCH scaffolds with directly absorbed BMP-2 (SCH-D) were investigated in parallel for comparison. In vitro release kinetics indicated that BMP-2 released from the SCH-L scaffold showed a significantly lower initial burst release, followed by a more sustained release over time than the SCH-D scaffold. In vitro cell viability, osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), and the in vivo osteogenic effect of scaffolds in a rat calvarial defect were evaluated. The results showed that compared with bare SCH and SCH-D scaffolds, the SCH-L scaffold significantly promoted the osteogenic differentiation of BMSCs in vitro and induced more pronounced bone formation in vivo. Further studies demonstrated that the mHANP-mediated satisfactory conformational change and sustained release benefited the protection of the released BMP-2 bioactivity, as confirmed by alkaline phosphatase (ALP) activity and a mineralization deposition assay. More importantly, the interaction of BMP-2/mHANPs enhanced the binding ability of BMP-2 to cellular receptors, thereby maintaining its biological activity in osteogenic differentiation and osteoinductivity well, which contributed to the markedly promoted in vitro and in vivo osteogenic efficacy of the SCH-L scaffold. Taken together, these results provide strong evidence that mHANPs represent an attractive carrier for binding BMP-2 to scaffolds. The SCH-L scaffold shows promising potential for bone tissue regeneration applications.

Controlled growth factor delivery system with osteogenic-angiogenic coupling effect for bone regeneration

“…During the early proliferation stage, VEGF and FGF-2 promote the expressions of BMP-2 receptors on cell surfaces [ 39 ], thereby enhancing the binding abilities of BMP-2 released in the later stages. Besides, the controlled release of BMP-2 is required for critical sized bone defects [ 40 ]. The burst and sustained release of BMP is necessary for the repair of bone defects.…”

Porous Nanomaterials Targeting Autophagy in Bone Regeneration

“…A variety of microporous (<2 nm), mesoporous (2~50 nm), and macropore nanomaterials (>50 nm) are designed as drug delivery carriers [41]. In particular, due to the high porosity and specific surface area, PNMs are widely used to deliver drugs for bone regeneration such as mesoporous silica nanoparticles [42][43][44] and mesoporous hydroxyapatite nanoparticles [29,30,45]. The hollow and mesoporous structure of nanomaterials can enhance drug loading efficiency [46].…”

“…Then, the crucial regulatory role of autophagy in bone regeneration is briefly introduced. The regulatory roles of PNMs, including mesoporous silica nanoparticles (MSNs) [20,26,27], mesoporous hydroxyapatite nanoparticles (HAP) [28][29][30], alumina nanoparticles (Al 2 O 3 ) [31,32], mesoporous bioactive glass nanoparticles (MBGNs) [33][34][35][36], mesoporous ceria (MCeO 2 ) [37,38], and metallic oxides [39,40] in bone regeneration via targeting autophagy, are reviewed and discussed.…”

Advances in porous inorganic nanomaterials for bone regeneration

“…Qiu et al fabricated a silk fibroin/chitosan scaffold loaded with mesoporous HA nanoparticles that provided a satisfactory delivery system for BMP-2. It exhibited satisfying mechanical properties and biocompatibility in a rat calvarial defect model [101]. Porous inorganic nanomaterials are reported to improve the mechanical performance of both natural polymers such as chitosan and silk [102,103] and synthetic polymers including polycaprolactone (PCL), polyethylene glycol (PEG), and poly(lactic-co-glycolic) acid (PLGA) [104].…”