Dynamic compression promotes proliferation and neovascular networks of endothelial progenitor cells in demineralized bone matrix scaffold seed

Abstract

<jats:p>Neovascularization is required for bone formation and successful fracture healing. In the process of neovascularization, endothelial progenitor cells (EPCs) play an important role and finish vascular repair through reendothelialization to promote successful fracture healing. In this study, we found that dynamic compression can promote the proliferation and capillary-like tube formation of EPCs in the demineralized bone matrix (DBM) scaffold seed. EPCs isolated from the bone marrow of rats have been cultured in DBM scaffolds before dynamic compression and then seeded in the DBM scaffolds under dynamic conditions. The cells/scaffold constructs were subjected to cyclic compression with 5% strain and at 1 Hz for 4 h/day for 7 consecutive days. By using MTT and real-time PCR, we found that dynamic compression can significantly induce the proliferation of EPCs in three-dimensional culture with an even distribution of cells onto DBM scaffolds. Both in vitro and in vivo, the tube formation assays in the scaffolds showed that the loaded EPCs formed significant tube-like structures. These findings suggest that dynamic compression promoted the vasculogenic activities of EPCs seeded in the scaffolds, which would benefit large bone defect tissue engineering.</jats:p>

Variations of circulating endothelial progenitor cells and transforming growth factor-beta-1 (TGF-β1) during thoracic radiotherapy are predictive for radiation pneumonitis

“…Others have recently demonstrated that vascular repair and reendothelialization after injury is enhanced by circulating EPCs [32,33]. Given these data, we speculate that 3D-CRT increases the mobilization of circulating EPCs, which may contribute to the repair of vascular and the enhancement of neoangiogenesis.…”

In vitro cyclic compressive loads potentiate early osteogenic events in engineered bone tissue

“…A strain of 2200 µε was chosen on the basis of optimal physiological strain range as reported by Yang et al and the frequency mimics the walking frequency observed in humans. Maximum strain used in our study (11,000 µε) is much lower than the strains applied in similar studies because those strains will be much beyond the elastic recovery of the polymeric scaffolds used in this study. And we used these MSC seeded PCL‐TCP scaffolds as relevant engineered tissue constructs and analyzed the effects of physiological compressive stains on cellular differentiation and mineralization.…”

“…Native bone tissues experience peak cyclic strains in the range of 0.2–0.35% and peak loading occurs around 1–3 Hz frequencies. Most of the previous cyclic loading studies have focused on loading parameters (strains ranging from 1 to 10%) that are much different from the physiological range . Furthermore, the substrate on which the cells are attached should replicate mechanical properties of native osteoinductive environment of the tissues to extract appropriate physiological response …”

Overcoming physical constraints in bone engineering: ‘the importance of being vascularized’

“…In addition, a possible link between mechanical stimulation and nutrition supply was demonstrated by the increased oxygen transport observed in MSCs embedded fibrin matrix stressed by moderate cyclic mechanical loading (Witt, Duda, Bergmann, & Petersen, 2014). Consistently, dynamic compression enhances the vasculogenic activities of circulating endothelial precursors (EPCs) seeded in the demineralized bone matrix scaffolds (Kong et al, 2012). The relationship between mechanical inputs and resulting biological tissue structure, composition, and metabolism is reported and discussed in several other papers and reviews (David et al, 2008;Desmoulin et al, 2013;Gardel, Serra, Reis, & Gomes, 2014;Gaspar, Gomide, & Monteiro;S.-T. Li et al, 2014;van Griensven et al, 2009).…”