BMP2-Mediated Silica Deposition: An Effective Strategy for Bone Mineralization

Abstract

The combined use of an osteogenic factor, such as bone morphogenetic protein 2 (BMP2), with a bone scaffold was quite functional for the reconstruction of bone defects. Although many studies using BMP2 have been done, there is still a need to develop an efficient way to apply BMP2 in the bone scaffold. Here, we reported an interesting fact that BMP2 has a silica deposition ability in the presence of silicic acid and proposed that such an ability of BMP2 can effectively immobilize and transport itself by a kind of coprecipitation of BMP2 with a silica matrix. The presence of BMP2 in the resulting silica was proved by SEM and EDS and was visualized by FITC-labeled BMP2. The delivery efficacy of BMP2 of silica-entrapped BMP2 on osteoblast differentiation and mineralization using MC3T3 E1 preosteoblast cells was evaluated in vitro. The coprecipitated BMP2 with silica exhibited osteogenesis at a low concentration that was insufficient to give an osteoinductive signal as the free form. Expectedly, the silica-entrapped BMP2 exhibited thermal stability over free BMP2. When applied to bone graft substitution, e.g., hydroxyapatite granules (HA), silica-entrapped BMP 2 laden HA (BMP2@Si/HA) showed sustained BMP2 release, whereas free BMP2 adsorbed HA by a simple dipping method (BMP2/HA) displayed a burst release of BMP2 at an initial time. In the rat critical-size calvarial defect model, BMP2@Si/HA showed better bone regeneration than BMP2/HA by about 10%. The BMP2/silica hybrid deposited on a carrier surface via BMP2-mediated silica precipitation demonstrated an increase in the loading efficiency, a decrease in the burst release of BMP2, and an increase in bone regeneration. Taken together, the coprecipitated BMP2 with a silica matrix has the advantages of not only being able to immobilize BMP2 efficiently without compromising its function but also serving as a stable carrier for BMP2 delivery.

Guidelines derived from biomineralized tissues for design and construction of high-performance biomimetic materials: from weak to strong

“…Last but not least, in addition to the structural elements in bone, some growth factors such as bone morphogenic protein-2 (BMP-2) have also been applied clinically to improve bone repair, 506–510 based on the guideline that these osteoinductive biomolecules can promote the formation of bone tissue. Transforming growth factor-beta and bone morphogenic protein signaling has fundamental roles in both embryonic skeletal development and postnatal bone homeostasis.…”

Biomineral-Based Composite Materials in Regenerative Medicine

“…The field of biomimetic silica formation has been becoming increasingly intriguing due to its potential to utilize gentle reaction conditions, control the silica structure, and facilitate relatively simple cargo loading [ 74 ]. The advancement of bio-inspired and biomimetic silica formation has been fueled by the identification of the molecules involved in natural silica biomineralization processes like silaffin peptides and polyamines [ 35 , 75 , 76 , 77 , 78 ].…”

“…This biosilica, which is rich in silanol groups, enhances the binding of growth factors with positively charged heparin-binding motifs compared to HAP [ 159 ]. In addition, the BMP2 protein itself has biosilica-forming properties, leading to the development of a BMP2 delivery system through self-encapsulation via BMP2-mediated silica synthesis [ 75 , 76 ]. BMP2/silica composites have demonstrated the sustained release of BMP2 from bone grafts.…”

Special Issue on Biomineralization: From Principles to Practices

“…24 Ki et al developed an effective strategy for bone mineralization by incorporating bone morphogenetic protein 2 (BMP2) into a silica matrix, serving as a stable carrier for BMP2 delivery and promoting osteogenesis at low concentrations. 25 In summary, advancing our understanding of the principles of biomineralization of shells, bones, and teeth will lead to the fabrication of newly developed biomaterials. The collected articles in this special issue do not comprehensively cover the topic of biomineralization from principles to applications, but we believe that these articles and all the presentations given at BIOMIN XVI and the biomineralization summit will inspire young researchers to gain new insights into biomineralization, explore its potential applications in life science/engineering, and solve other global issues in the near future.…”

“…Julian et al reported a dentin replacement material, an apatite–gelatin nanocomposite, which was significantly strengthened by effective cross-linking with transglutaminase and casein, resulting in a Vickers hardness that is comparable to that of human dentin . Ki et al developed an effective strategy for bone mineralization by incorporating bone morphogenetic protein 2 (BMP2) into a silica matrix, serving as a stable carrier for BMP2 delivery and promoting osteogenesis at low concentrations …”