Potentiating bioactivity of BMP‐2 by polyelectrolyte complexation with sulfonated polyrotaxanes to induce rapid bone regeneration in a mouse calvarial defect

Abstract

Bone reconstruction is a challenging issue in the regeneration of surgically removed bone and disease-related bone defects. Although bone morphogenetic protein-2 (BMP-2) has received considerable attention as a bone regeneration inducer, a high dose of BMP-2 is typically required due to its short life-time under in vivo conditions. We have proposed a method to enhance the osteogenetic differentiation ability of BMP-2 in vitro that is based on supramolecular polyelectrolyte complexation with sulfonated polyrotaxanes (PRXs) consisting of sulfopropyl ether (SPE)-modified α-cyclodextrins threaded along a poly(ethylene glycol) chain capped with terminal bulky stopper molecules. In this study, we evaluated the in vivo bone regeneration ability of the SPE-PRX/BMP-2 complexes in a mouse calvarial defect model in comparison to free BMP-2 and heparin/BMP-2 complexes. The regenerated bone area was determined by X-ray computed microtomography, and the mice implanted with sulfonated PRX/BMP-2 complexes exhibited rapid and significant bone regeneration compared to those implanted with free BMP-2 and heparin/BMP-2 complexes. We concluded that the sulfonated PRX/BMP-2 complexes are a promising candidate for clinical bone regeneration. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1355-1363, 2017.

Polyelectrolyte Complexes between Polycarboxylates and BMP-2 for Enhancing Osteogenic Differentiation: Effect of Chemical Structure of Polycarboxylates

“…Although this approach has been recognized as a gold standard for bone reconstruction, the collection of bone grafts is generally invasive for patients. As an alternative method to bone grafting, various approaches to stimulate bone regeneration have been investigated, such as artificial bone substitute materials (e.g., β-tricalcium phosphate and hydroxyapatite) [4,5] and pharmacological molecules (e.g., growth factors and low-molecular-weight drugs) [6,7,8,9,10]. Bone morphogenetic protein 2 (BMP-2), a secreted growth factor that belongs to the transforming growth factor-β (TGF-β) superfamily, has attracted considerable attention because of its strong osteoinductivity [11,12].…”

Maxillary Bone Regeneration Based on Nanoreservoirs Functionalizedε-Polycaprolactone Biomembranes in a Mouse Model of Jaw Bone Lesion

“…Beyond the maxillary location, it will be possible to analyze the bone response of Ta mice in other anatomical locations, as calvaria or long bones. Significative osteoinduction using BMP-2 was demonstrated in other animal models in calvaria like rabbit or mice [ 37 , 38 ].…”

Cellular Fragments as Biomaterial for Rapid In Vitro Bone-Like Tissue Synthesis

“…A widely accepted concept is that osteoblasts and chondrocytes, when induced to differentiate into mature cells, start to secrete matrix vesicles (MVs), which are known to be the nucleation site for mineral formation [13,14]. In an attempt to promote more rapid bone tissue synthesis, researchers have therefore, customized a combination of stem cells, scaffolds and growth factors (e.g., bone morphogenetic proteins (BMPs)) or alternative biofunctional molecules (e.g., statins, menaquinone-4) [15][16][17][18][19], though all these processes are still time-consuming and costly. Other techniques involve the utilization of pre-osteoblastic or pre-osteocytic cell lines, such as MLO-A5 cells, which can promote bone-like mineral formation within seven days of culture [20].…”