Bioactive gel self-assembled from phosphorylate biomimetic peptide: A potential scaffold for enhanced osteogenesis.

Bone morphogenetic protein-2 biomimetic peptide (BMPBP) is a potent osteoinductive cytokine and plays a critical role during bone regeneration. Efforts to prepare hydrogels with surface modification or physical absorption of bioactive molecules do not provide sufficient bioactivity to meet the requirements of clinical application. The goal of this study was to form a three-dimensional hydrogel comprised of BMP-2 core sequence oligopeptide, phosphoserine, a synthetic cell adhesion peptide (RGDS), and polyaspartic acid to synergistically promote osteogenesis. Experiments performed in vitro revealed that the peptide gel was conducive to adhesion and proliferation of rat marrow mesenchymal stem cells (rMSCs). In addition, RT-PCR analysis indicated that rMSCs allowed better expression of osteogenesis-related genes such as BMP-2, runt-related transcription factor 2 (RUNX2), alkaline phosphatase (ALP), osteocalcin (OCN), and osteopontin (OPN). Use of the rat cranial bone defects model with micro-CT 3D reconstruction showed that bone regeneration patterns occurred from one side edge toward the center of the area implanted with the prepared biomimetic peptide hydrogels, demonstrating significantly accelerated bone regeneration. This work will provide a basis to explore the further application potential of this bioactive scaffold.

Bioactive 3D scaffolds self-assembled from phosphorylated mimicking peptide amphiphiles to enhance osteogenesis.

Being an active scaffold in bone tissue engineering, hydrogel self-assembled from biomimetic peptide amphiphile (PA) has excellent ability to induce osteogenic differentiation and osteogenesis. Here, a multifunctional scaffold based on bone morphogenetic protein-2 (BMP-2) mimicking peptide, RGDS, and phosphoserine has been developed to enhance osteogenesis. Cell experiments in vitro displayed that the hydrogel could effectively promote rat messenchymal stem cells (rMSCs) proliferation and induce them differentiation into oesteblasts. The up-regulated RNA expression of osteogenic marker genes, like BMP-2, osteopontin (OPN), osteocalcin (OCN) and runt-related transcription factor 2 (Runx2) revealed that the scaffold could accelerate rMSCs differentiation at RNA level. Further studies on rat skull defect model demonstrated that the multifunctional scaffold exhibited excellent repair ability due to a potential synergistic effect of biomimetic peptide and phosphoserine. Histochemical/immunohistochemical staining results showed that expressions of alkaline phosphatase (ALP) and OCN was significantly up-regulated, indicating that the hydrogel could accelerate maturation of osteoblast precursors during the whole repairing process and be a promising bioactive scaffold for bone repairing.

Biological Activity of an Injectable Biphasic Calcium Phosphate/PMMA Bone Cement for Induced Osteogensis in Rabbit Model.

Polymethylmethacrylate (PMMA) bone cement is widely used in repair of vertebral fracture because of its good biomechanical properties and fast curing. However, the bioinertness of PMMA cement may cause interfacial loosening, fatigue, fracture, and ultimate failure. In this study, biphasic calcium phosphate (BCP) is introduced into PMMA cement to prepare an injectable composite bone cement (BCPx /PMMA) and the content of BCP is optimized to achieve appropriate rate of absorption that matches the bone regeneration. The compressive strength of BCPx /PMMA bone cement is found to comply with the International Standardization Organization standard 5833, and can promote biomineralization as well as adhesion, proliferation, and osteogenic differentiation of Sprague-Dawley rat bone marrow mesenchymal stem cells in vitro. Furthermore, in vivo test performed on a rabbit radius defect model demonstrates that the presence of BCP can significantly improve the osteogenic efficacy of PMMA cement. Therefore, it is anticipated that BCPx /PMMA bone cement, as a promising injectable biomaterial, is of great potential in bone tissue regeneration.

Effect of modification degree of nanohydroxyapatite on biocompatibility and mechanical property of injectable poly(methyl methacrylate)-based bone cement.

The objective of this study is to prepare a biocompatible nanohydroxyapatite/poly(methyl methacrylate) (HA/PMMA) composite bone cement, which has good mechanical property and can be used for vertebroplasty. Up to 40 wt % of nanohydroxyapatite (nano-HA) in the power, which was surface modified with poly(methylmethacrylate-co-γ-methacryloxypropyl timethoxysilane) [P(MMA-co-MPS)] copolymer, was incorporated into the composite bone cement. The content of P(MMA-co-MPS) on the surface of nano-HA (18.7%, 22.8%, and 26%) was determined through thermogravimetric analysis (TGA). The morphology of biomineralized surface of composite bone cement was observed under scanning electron microscope (SEM). The mechanical measurements of the composite cements implied that the interfacial interaction between the HA and PMMA matrix may be greatly enhanced after surface modification of HA. Biochemical assays indicated that the HA/PMMA bone cement had no cytotoxicity and induced no hemolysis. The cell adhesion and alkaline phosphatase (ALP) activity assays indicated that the biocompatibility of HA/PMMA bone cement could be promoted, demonstrating that it can be used as an ideal weight-bearing bone repair materials on clinical application.