Stimuli-responsive Co-delivery System Embedded Polymeric Nanofibers with Synergistic Effects of Growth Factors and Low-intensity Pulsed Ultrasound to Enhance Osteogenesis Properties

Synthetic biomaterial scaffolds with a single component cannot provide all the prerequisites for efficient tissue regeneration. Direct loading of bioactive factors into these scaffolds may lead to an unwanted burst release or impaired activities. The combination of nanomaterials with scaffolds can offer tremendous potential and opportunities to address such problems. In this study we aimed to provide an ideal scaffold, that can be implanted in the bone defect area, allowing effective cell adhesion, and directional differentiation to develop new tissues. To achieve this goal, we designed and synthesized a series of biocompatible and biodegradable scaffolds, for controlled co-delivery of curcumin (CUR) and recombinant human bone morphogenic protein-2 (rhBMP-2) loaded Dendritic Silica/Titania Mesoporous incorporated PCL/PEG nanofiber (CUR-rhBMP2@DSTNs/PCL-PEG). The scaffolds were also subjected to low-intensity pulsed ultrasound (LIPUS) stimulation to improve new bone formation. The weight ratios of polymers and nanoparticles were optimized to provide desirable textural porosity, pore size, fiber diameter, and mechanical features. Advanced characterization methods were used to investigate the surface structure, thermal stability, chemical composition, and crystalline structure of the drug/nanocarrier and scaffolds.
The in vitro release studies of CUR and BMP-2 from the scaffolds under different conditions (physical and ultrasound irradiation) provide information on the drug release kinetics and efficiency of the US-stimuli delivery system. The results show that the system can deliver drugs in response to ultrasound irradiation, making it a promising system for targeted drug delivery in the future.
In addition to evaluating drug release, we assessed the in vitro biocompatibility of the scaffolds. Specifically, we studied cell viability, mineralization, and the expression of osteogenic markers. Our findings indicated that the scaffold, in combination with ultrasound stimulation and growth factor release, exhibited potential for inducing osteogenic differentiation. Furthermore, the incorporation of silica/titania-based nanoparticles enhanced mineralization and the expression of osteogenic markers.