Platelet-derived biomaterials-mediated improvement of bone injury through migratory ability of embryonic fibroblasts: in vitro and in vivo evidence

Abstract

Bony injuries lead to compromised skeletal functional ability which further increase in aging population due to decreased bone mineral density. Therefore, we aimed to investigate the therapeutic potential of platelet-derived biomaterials (PDB) against bone injury. Specifically, we assessed the impact of PDB on osteo-inductive characteristics and migration of mouse embryonic fibroblasts (MEFs). Osteogenic lineage, matrix mineralization and cell migration were determined by gene markers (RUNX2, OPN and OCN), alizarin Red S staining, and migration markers (FAK, pFAK and Src) and EMT markers, respectively. The therapeutic impact of TGF-β1, a key component of PDB, was confirmed by employing inhibitor of TGF-β receptor I (Ti). Molecular imaging-based in vivo cellular migration in mice was determined by establishing bone injury at right femurs. Results showed that PDB markedly increased expression of osteogenic markers, matrix mineralization, migration and EMT markers, revealing higher osteogenic and migratory potential of PDB-treated MEFs. In vivo cell migration was manifested by expression of migratory factors, SDF-1 and CXCR4. Compared to control, PDB-treated mice exhibited higher bone density and volume. Ti treatment inhibited both migration and osteogenic potential of MEFs, affirming impact of TGF-β1. Collectively, our study clearly indicated PDB-rescued bone injury through enhancing migratory potential of MEFs and osteogenesis.

Autologous Bioactive Compound Concentrated Growth Factor Ameliorates Fistula Healing of Anal Fistula in a Pig Model and Promotes Proliferation and Migration of Human Skin Fibroblasts via Regulating the MEK/ERK Pathway

“…Consistent with the previous studies, our results have demonstrated that CGF promotes HSF migration, increases the protein levels of COL1A1, COL3A1, and TIMP-1 and inhibits the protein level of MMP-3. Although there is no direct evidence that CGF regulates cell EMT, platelet-derived biomaterials have been proved to improve bone injury by promoting EMT and enhancing the migratory ability of embryonic fibroblasts [ 39 ]. In this study, CGF, also a platelet-derived biomaterial, was able to promote vimentin expression and inhibit E-cadherin expression in granulation tissue and HSF, indicating that CGF accelerated wound healing by promoting the EMT process.…”

“…Growing evidence suggests that MEK/ERK pathway can induce cell proliferation and survival according to the various specific extracellular stimuli. CGF contains a large amount of EGF, and the binding of EGF to EGFR will lead to the activation of the downstream MEK/ERK pathway involved in the regulation of cell proliferation and metastasis [ 39 , 40 ]. Furthermore, the pharmacological mechanism of some drugs for wound healing is associated with the activation of the MEK/ERK pathway [ 41 , 42 ].…”

Addressing local bone loss in the proximal femurs of women at high risk of fracture

“…The majority of these procedures have been tested only on murine animal models, including deproteinized bone added with VEGF gene transfer plasmid that provides bone regenerative effects through the enhancement of local angiogenesis, platelet-derived biomaterials endowed with bone healing properties thanks to the migratory ability of embryonic fibroblasts, autologous adipose-derived stem cell-seeded scaffolds that increase femoral strength and bone density in osteoporotic rats, and injectable nano-reinforced bone cement with controlled biodegradability and osteoconductive effect [37][38][39][40] .…”

Crosstalk between Macrophages and Mesenchymal Stem Cells Regulated by Biomaterials and Its Role in Bone Regeneration

“…e presentation of growth factors, such as BMP-2, TGF-β1, and FGF2, to MSCs, has been found to target Runx2 and to activate and regulate osteogenesis [72][73][74]. In addition to proosteogenic effects, the supply of Nel-like protein type I (NELL-1) significantly reduced adipose differentiation of ADSCs while promoting osteogenic differentiation [75,76].…”