Effects of a novel self-assembling peptide scaffold on bone regeneration and controlled release of two growth factors.

RADA16 is a self-assembling peptide material with good bioactivity. To improve the bioactivity of a material, some specific functional motifs can be added to its peptide sequence. Here, we report a self-assembling peptide nanogel, RADA16-RGD, that has better bioactivity than RADA16 and can simultaneously carry and control the release of two growth factors, VEGF and BMP-2, which have synergistic effects on bone formation. The peptide materials were characterized by transmission electron microscopy and scanning electron microscopy. The mechanical properties of the peptides were evaluated by the rheology test. The biocompatibility of the materials was evaluated via the use of the CCK-8 test, live/dead staining and confocal laser scanning microscopy. Osteogenesis capability in vitro was evaluated by means of ALP staining, extracellular matrix mineralization and detection of osteogenic markers. The controlled release of growth factors was examined by ELISA. The results showed that RADA16-RGD exhibited a better ability than RADA16 to promote cell proliferation, adhesion and bone formation. In addition, RADA16-RGD had good biocompatibility and exhibited effective controlled release of VEGF and BMP-2. More importantly, compared with RADA16-RGD loaded with single growth factor or without growth factors, RADA16-RGD loaded with two growth factors exhibited a stronger ability to promote cell proliferation and osteogenesis. This study provides a promising strategy for the application of self-assembling peptides to promote osteogenesis and controlled release of proteins.

FGF19 protects against obesity-induced bone loss by promoting osteogenic differentiation.

Human fibroblast growth factor 19 (FGF19) has become a potential therapeutic target for metabolic-related diseases. However, the effects of FGF19 on obesity-induced bone loss have not been completely elucidated. The aim of this study was to investigate the protective effects of FGF19 in high-fat diet (HFD)-fed obese mice and palmitic acid (PA)-treated osteoblasts and to further explore its underlying mechanisms. In vivo, we found that FGF19 alleviated the decreased bone mineral density (BMD) induced by HFD. Micro-CT analysis of femur samples and histological analysis indicated that FGF19 alleviated HFD-induced loss of bone trabeculae and damage to the bone trabecular structure. In vitro, the results suggested that FGF19 ameliorated the PA-induced decline in osteoblast proliferation, increased cell death and impaired cell morphology. Additionally, FGF19 protected against the decline in activation of alkaline phosphatase (ALP) and protein expression of Collagen-1, Runx-2, and osteopontin (OPN) induced by PA. Furthermore, FGF19 might enhance osteogenic differentiation via the Wnt/ß-catenin pathway and inhibit osteoclastogenesis by regulating the osteoprotegerin (OPG)/receptor activator of NF-κB ligand (RANKL) axis, thus attenuating the negative effect of PA in osteoblasts. In conclusion, our results suggested that FGF19 might promote osteogenic differentiation partially through activation of the Wnt/ß-catenin pathway and alleviate obesity-induced bone loss.

A novel biocomposite scaffold with antibacterial potential and the ability to promote bone repair.

Clinical treatment of bone defects caused by trauma, tumor resection and other bone diseases, especially bone defects that can lead to infection, remains a major challenge. Currently, autologous bone implantation is the gold standard for treatment of bone defects, but it is limited by secondary trauma and insufficient autologous material. Moreover, postoperative infection is an important factor affecting bone healing.AcN-RADARADARADARADA-CONH2 (RADA) is a new type of self-assembling peptide(SAP) composed of Arg,Ala,Asp and other amino acids was designed and prepared. The "RADA" self-assembling peptide hydrogels has excellent biological activity and it's completely biodegradable and non-toxic.It is also have been confirmed to promote cell proliferation, wound healing, tissue repair, and drug delivery. To promote bone regeneration and simultaneously prevent bacterial infection, we designed biocomposite scaffolds comprising RADA and calcium phosphate cement (CPC), termed RADA-CPC. The morphological features of the scaffold were characterized by scanning electron microscopy (SEM). In vitro studies demonstrated that RADA-CPC enhances osteoblast proliferation, differentiation and mineralization. In addition, the scaffold was used as a drug delivery system to treat postoperative infections by sustained release of ciprofloxacin (CIP). The RADA-CPC scaffold may have potential application prospects in orthopedics field because of its role in promoting bone repair and as a sustained-release drug carrier to prevent infections.