Hydroxyapatite-filled osteoinductive and piezoelectric nanofibers for bone tissue engineering

Abstract

Osteoporotic-related fractures are among the leading causes of chronic disease morbidity in Europe and in the US. While a significant percentage of fractures can be repaired naturally, in delayed-union and non-union fractures surgical intervention is necessary for proper bone regeneration. Given the current lack of optimized clinical techniques to adequately address this issue, bone tissue engineering (BTE) strategies focusing on the development of scaffolds for temporarily replacing damaged bone and supporting its regeneration process have been gaining interest. The piezoelectric properties of bone, which have an important role in tissue homeostasis and regeneration, have been frequently neglected in the design of BTE scaffolds. Therefore, in this study, we developed novel hydroxyapatite (HAp)-filled osteoinductive and piezoelectric poly(vinylidene fluoride-co-tetrafluoroethylene) (PVDF-TrFE) nanofibers via electrospinning capable of replicating the tissue’s fibrous extracellular matrix (ECM) composition and native piezoelectric properties. The developed PVDF-TrFE/HAp nanofibers had biomimetic collagen fibril-like diameters, as well as enhanced piezoelectric and surface properties, which translated into a better capacity to assist the mineralization process and cell proliferation. The biological cues provided by the HAp nanoparticles enhanced the osteogenic differentiation of seeded human mesenchymal stem/stromal cells (MSCs) as observed by the increased ALP activity, cell-secreted calcium deposition and osteogenic gene expression levels observed for the HAp-containing fibers. Overall, our findings describe the potential of combining PVDF-TrFE and HAp for developing electroactive and osteoinductive nanofibers capable of supporting bone tissue regeneration.

Direct coupled electrical stimulation towards improved osteogenic differentiation of human mesenchymal stem/stromal cells: a comparative study of different protocols

“…8 ), resulting in the observed lower ALP activity and Runx2 and ALP gene expressions. Accordingly, our results are also in line with previous BTE studies reporting decreased ALP activity as a result of a more advanced osteogenic differentiation stage of the MSCs 45 , 46 .…”

Bioactive Nanofibrous Scaffolds Incorporating Decellularized Cell-Derived Extracellular Matrix for Periodontal Tissue Engineering

“…The presence of calcium and phosphorus on electrospun scaffolds was further confirmed through elemental analysis. Moreover, PCL-CTS and PCL-CTS-ECM electrospun scaffolds presented mineral deposits secreted by PDLSCs with Ca/P ratios of 1.78 and 2.25, respectively, which are within the range of values reported for the human bone tissue. , Visualization and quantification of cell mineralization, specifically the hydroxyapatite portion of bone-like nodules deposited by cells, showed higher levels of PCL-CTS and PCL-CTS-ECM in comparison to PCL scaffolds (OsteoImage staining). Notably, these results are in accordance with previous works that have shown that dECM enhances the osteogenic differentiation of MSCs. ,, In particular, Heng and colleagues have shown that PDLSC-derived ECM enhances adhesion, proliferation, and osteogenic induction of human dental pulp stem cells, by increasing calcium deposition and ALP activity …”

3D Printed Piezoelectric BaTiO3/Polyhydroxybutyrate Nanocomposite Scaffolds for Bone Tissue Engineering

“…The ultimate purpose of this research was to improve the mechanical and piezoelectric properties of plain PHB and to demonstrate the nanocomposite printability into porous scaffolds that could be suitable for bone tissue engineering application. In fact, having a mechanically strong piezoelectric scaffold mainly composed of a biodegradable polymer is thought to enhance new bone formation once implanted in vivo, thus overcoming the limits of PVDF-based scaffolds, which have less suited mechanical properties and do not biodegrade [51].…”