Polyhedral microcrystals encapsulating bone morphogenetic protein 2 improve healing in the alveolar ridge

Abstract

Atelocollagen sponges incorporating polyhedra encapsulating bone morphogenetic protein 2 (BMP-2) were implanted into lateral bone defects in the mandible. Half of the bone defects on the left side were treated with atelocollagen sponges containing 1.8 × 10(7) BMP-2 polyhedra, and half were treated with sponges containing 3.6 × 10(6) BMP-2 polyhedra. As controls, we treated the right-side bone defects in each animal with an atelocollagen sponge containing 5 µg of recombinant human BMP-2 (rhBMP-2) or 1.8 × 10(7) empty polyhedral. After a healing period of six months, whole mandibles were removed for micro-computed tomography (CT) and histological analyses. Micro-CT images showed that more bone had formed at all experimental sites than at control sites. However, the density of the new bone was not significantly higher at sites with an atelocollagen sponge containing BMP-2 polyhedra than at sites with an atelocollagen sponge containing rhBMP-2 or empty polyhedra. Histological examination confirmed that the BMP-2 polyhedra almost entirely replaced the atelocollagen sponges and connected the original bone with the regenerated bone. These results show that the BMP-2 delivery system facilitates the regeneration of new bone in the mandibular alveolar bone ridge and has an advance in the technology of bone regeneration for implant site development.

Sustained delivery of the bone morphogenetic proteins BMP-2 and BMP-7 for cartilage repair and regeneration in osteoarthritis

“…This work builds on previous data where pBMP-2 incorporated into an absorbable collagen sponge (ACS) promoted bone formation to repair a critical-sized defect in a rat calvaria model, with superior efficacy to conventional rBMP-2 [ 26 ]. Furthermore, incorporation of pBMP-2 into an atelocollagen sponge facilitated the regeneration of new bone in the mandibular alveolar bone ridge [ 35 ].…”

Bioengineered silkworms with butterfly cytotoxin-modified silk glands produce sericin cocoons with a utility for a new biomaterial

“…Absorbable collagen sponges or atelocollagen sponges, both of which incorporated polyhedron-encapsulated bone morphogenetic protein-2, have been shown to be effective for the complete and rapid healing of critically sized bone defects in mammals, highlighting the effectiveness of combining polyhedronencapsulated cytokines with biocompatible 3D substitutes to fabricate extracellular matrices that can control in vivo cell activities (26,28,29). However, scaffolds containing mammal-derived components, such as collagen or coagulation factor XIII, may present risks when used in human bodies because they could be contaminated by prions or viruses.…”

“…We previously showed that the activity of cytokines encapsulated in polyhedra, which are protein microcrystals of cypovirus, can be stably maintained over long periods in both ex vivo and in vivo environments, and can be slowly released to stimulate the growth and differentiation of many cell types continually (14,(24)(25)(26)(27)(28)(29). Therefore, to determine whether sericin hydrogels can act as scaffolds to support cell growth and differentiation, we cultivated the mouse embryonic stem (ES) cell line EB5 on sericin hydrogels that were overlaid with a medium containing canonical recombinant human leukemia inhibitory factor (rhLIF) or that incorporated polyhedron-encapsulated LIF (24) (SI Appendix, SI Materials and Methods).…”

DC-STAMP: A Key Regulator in Osteoclast Differentiation

“…Collectively, our data suggest that DC‐STAMP, together with MMP‐2 and MMP‐9 (Galliera et al, ; Rocha et al, ), can be a useful tool for monitoring, in parallel with other bone turnover markers, to evaluate bone remodeling and tissue healing. Given that DC‐STAMP+ cells are homing to bone fracture sites, a step forward approach is to molecular engineer a chimeric DC‐STAMP protein by which DC‐STAMP is able to bring small peptides/proteins such as bone morphogenetic protein 2 (BMP‐2) or MMP‐9 (Kim et al, ; Matsumoto et al, ; Miller et al, ; Saito et al, ; Wang et al, ) with healing‐promoting effects to bone fracture sites.…”