Abstract
The main limitation of tissue engineering lies in the inability to stimulate osteogenesis, angiogenesis of stem cells and broad-spectrum antimicrobial activity. However, the development of multifunctional bioactive materials with these capabilities remains a great challenge. In this study, we prepared mesoporous silica nanoparticles encapsulated with silver nanocrystals (AG-MSN) with uniform sphere size and mesopores. Platelet-derived growth factor BB (PDGF-BB) was effectively loaded in the AG-MSN mesopores (P-AG-MSN). The silicon ions (Si) released by P-AG-MSN stimulate osteogenic differentiation of bone marrow stromal cells (BMSC) by activating the alkaline phosphatase (ALP) activity of bone-related genes and increasing protein (OCN, RUNX2 and OPN) expression. Ag+ ions could be slowly released from the interior of the shell, highlighting their durable antibacterial activity. The sustained release of PDGF-BB from P-AG-MSN stimulated the angiogenic differentiation of BMSC, as indicated by the enhanced secretion of vascular endothelial growth factor (VEGF), HIF-1α, HGF and ANG-1 and protein expression. Our results show that P-AG-MSN can clearly promote BMSC osteostimulation and vascularization. This research serves as a preliminary study of the utilization of this multifunctional mixture to fabricate a new active biological scaffold that integrates BMSC osteostimulation, vascularization and bactericidal effects by 3D printing technology.
Highlights
The clinical treatment of large segmental bone defects after splintered fracture, tumor resection, or cleaning of osteomyelitis lesions remains a great challenge for orthopedists
The results further revealed that the expression levels of OCN, OPN and RUNX2 were increased depending on nanosphere concentration, especially the P-AG-Mesoporous silica nanoparticles (MSNs) concentration
The results showed that the MBCs of P-AG-MSN against Escherichia coli, Pseudomonas aeruginosa and Candida sporogenes were 50/400/100 μg/100 mL, respectively; P-AG-MSN exhibited poor bactericidal effects against Staphylococcus aureus
Summary
The clinical treatment of large segmental bone defects after splintered fracture, tumor resection, or cleaning of osteomyelitis lesions remains a great challenge for orthopedists. Over the past several years, the treatment of bone defects, including those caused by trauma, tumor, infection or genetic malformation, using multifunctional bioactive materials has attracted extensive attention.[1,2,3] To repair large segmental bone defects, this biological material should feature properties that include osteostimulation (promoting new bone formation), angiostimulation (inducing vascularization) and the capacity to provide defense against bacterial infection.[4,5,6,7] few synthetic scaffold materials can satisfy all of these properties simultaneously. An insufficient blood supply to the bone tissue engineered during the initial graft period would block the nutrient supply and excretion of metabolic products, disturbing the signal transmission among cells and destabilizing the intercellular environment, affecting the regeneration of bone tissues.[10,11] Currently, a relatively promising strategy for the vascularized tissue engineering of bone is to jointly culture cells with angioblastic ability and multipotential stem cells to establish vascularized tissue engineering bone. [12] To achieve the multi-functional properties of bone-repairing materials, we propose a single biomaterial system that can induce the multi-directional differentiation of mesenchymal stem cells and provide effective infection control
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