Local Application of Mineral-Coated Microparticles Loaded With VEGF and BMP-2 Induces the Healing of Murine Atrophic Non-Unions

Deficient angiogenesis and disturbed osteogenesis are key factors for the development of nonunions. Mineral-coated microparticles (MCM) represent a sophisticated carrier system for the delivery of vascular endothelial growth factor (VEGF) and bone morphogenetic protein (BMP)-2. In this study, we investigated whether a combination of VEGF- and BMP-2-loaded MCM (MCM + VB) with a ratio of 1:2 improves bone repair in non-unions. For this purpose, we applied MCM + VB or unloaded MCM in a murine non-union model and studied the process of bone healing by means of radiological, biomechanical, histomorphometric, immunohistochemical and Western blot techniques after 14 and 70 days. MCM-free non-unions served as controls. Bone defects treated with MCM + VB exhibited osseous bridging, an improved biomechanical stiffness, an increased bone volume within the callus including ongoing mineralization, increased vascularization, and a histologically larger total periosteal callus area consisting predominantly of osseous tissue when compared to defects of the other groups. Western blot analyses on day 14 revealed a higher expression of osteoprotegerin (OPG) and vice versa reduced expression of receptor activator of NF-κB ligand (RANKL) in bone defects treated with MCM + VB. On day 70, these defects exhibited an increased expression of erythropoietin (EPO), EPO-receptor and BMP-4. These findings indicate that the use of MCM for spatiotemporal controlled delivery of VEGF and BMP-2 shows great potential to improve bone healing in atrophic non-unions by promoting angiogenesis and osteogenesis as well as reducing early osteoclast activity.

Bone morphogenetic protein 1.3 inhibition decreases scar formation and supports cardiomyocyte survival after myocardial infarction

Despite the high prevalence of ischemic heart diseases worldwide, no antibody-based treatment currently exists. Starting from the evidence that a specific isoform of the Bone Morphogenetic Protein 1 (BMP1.3) is particularly elevated in both patients and animal models of myocardial infarction, here we assess whether its inhibition by a specific monoclonal antibody reduces cardiac fibrosis. We find that this treatment reduces collagen deposition and cross-linking, paralleled by enhanced cardiomyocyte survival, both in vivo and in primary cultures of cardiac cells. Mechanistically, we show that the anti-BMP1.3 monoclonal antibody inhibits Transforming Growth Factor β pathway, thus reducing myofibroblast activation and inducing cardioprotection through BMP5. Collectively, these data support the therapeutic use of anti-BMP1.3 antibodies to prevent cardiomyocyte apoptosis, reduce collagen deposition and preserve cardiac function after ischemia.

Surface Modification of Polycaprolactone Scaffold With Improved Biocompatibility and Controlled Growth Factor Release for Enhanced Stem Cell Differentiation

Polycaprolactone (PCL) has been widely used as a scaffold material for tissue engineering. Reliable applications of the PCL scaffolds require overcoming their native hydrophobicity and obtaining the sustained release of signaling factors to modulate cell growth and differentiation. Here, we report a surface modification strategy for electrospun PCL nanofibers using an azide-terminated amphiphilic graft polymer. With multiple alkylation and pegylation on the side chains of poly-L-lysine, stable coating of the graft polymer on the PCL nanofibers was achieved in one step. Using the azide-alkyne “click chemistry”, we functionalized the azide-pegylated PCL nanofibers with dibenzocyclooctyne-modified nanocapsules containing growth factor, which rendered the nanofiber scaffold with satisfied cell adhesion and growth property. Moreover, by specific immobilization of pH-responsive nanocapsules containing bone morphogenetic protein 2 (BMP-2), controlled release of active BMP-2 from the PCL nanofibers was achieved within 21 days. When bone mesenchyme stem cells were cultured on this nanofiber scaffold, enhanced ossification was observed in correlation with the time-dependent release of BMP-2. The established surface modification can be extended as a generic approach to hydrophobic nanomaterials for longtime sustainable release of multiplex signaling proteins for tissue engineering.

Therapeutic Mechanism of Chinese Medicine on the Healing of Early and Middle Fractures in Rabbits Under the Expression Level of Bone Morphogenetic Protein-2 (BMP-2) in Bone Tissue

In order to explore the therapeutic mechanism of Chinese medicine on the healing of rabbits early and middle fractures, a rabbit fracture model was established in this study. The study was divided into several groups, i.e., treatment group (TG) (fed with Chinese medicine Capsule) and control group (CG) (fed with normal saline (NS)). The materials were collected at 1, 3, and 5 weeks after the start of the experiment for analysis. The experiment content included: callus Hematoxylin-Eosin staining (HE staining); Bone Morphogenetic protein-2 (BMP-2) protein level detection; Type I and type II bone collagen (BC) detection; and serum biochemical factors detection. The experimental results showed that the formation of callus in the TG was better than in the CG; the BMP-2 protein expression level in the TG was higher than in the CG, and there were statistically significant differences (SSDs); the type I and type II BC levels in the TG were higher than the CG, there were SSDs; the levels of serum calcium (SC), phosphorus ion (PI), and alkaline phosphatase (ALP) in the TG were also higher than in the CG, and there were SSDs.