Hypoxia-Mimicking Nanofibrous Scaffolds Promote Endogenous Bone Regeneration

Abstract

Utilizing biomimetic materials to potentiate endogenous cell growth or signaling is superior to relying on exogenous cells or signals for bone formation. Desferoxamine (DFO), which is a hypoxia-mimetic agent that chelates iron (Fe3+), mimics hypoxia to encourage bone healing. However, high cytotoxicity, off-target effects, and the short half-life of DFO have significantly impeded its further applications. We mitigated these side effects by locally immobilizing DFO onto a gelatin nanofibrous (GF) scaffold that retained DFO’s ability to chelate Fe3+. Moreover, DFO-functionalized GF (GF-DFO) scaffolds, which have similar micro/macrostructures to GF scaffolds, not only demonstrated decreased cytotoxicity on both human umbilical vein endothelial cells and human mesenchymal stem cells but also significantly increased vascular endothelial growth factor (VEGF) expression in vitro. Most importantly, in our in vivo experiments on a critical-sized cranial bone defect mouse model, a significant amount of bone was formed in most of the GF-DFO scaffolds after six weeks, while very little new bone was observed in the GF scaffolds. These data suggest that use of a hypoxia-mimicking nanofibrous scaffold is a promising strategy for promoting endogenous bone formation.

BBP-functionalized biomimetic nanofibrous scaffolds can capture BMP2 and promote osteogenic differentiation

“…, BMPs) for bone regeneration. Our most recent studies proved that the hypoxia-mimicking GF scaffold could promote cranial bone regeneration without the addition of exogenous cells or BMPs, potentially through the stimulation of endogenous BMPs and angiogenic signals in situ [59]. Our current findings suggest that it is possible to promote endogenous bone formation by the BBP-functionalized biomimetic GF scaffolds through the stimulation, capture and sustained release of endogenous BMPs in situ , although a higher amount of BBP may need to be incorporated on the scaffolds to achieve satisfactory bone formation in vivo .…”

Mineralized nanofibrous scaffold promotes phenamil‐induced osteoblastic differentiation while mitigating adipogenic differentiation

“…3D GF scaffolds were prepared using paraffin spheres according to previous reports (Y. Liu, Yao, & Sun, ; Q. Yao, Liu, & Sun, ; Q. Yao, Liu, Tao, Baumgarten, & Sun, ) with some modifications. Briefly, 1.0 g paraffin spheres with a diameter size between 300 and 500 μm were added to Teflon molds (ϕ17‐mm cylinder) and preheated at 37°C for 28 min.…”

“…The morphology and microstructure of 3D scaffolds were characterized through Quanta standard environmental SEM (FEI, United States). Mechanical compression used MTS insight (MTS, Minnesota, USA) machine according to previous reports (X. Liu & Ma, ; Xu, Miszuk, Zhao, Sun, & Fong, ; Q. Yao et al, ) with some modifications. Briefly, a sample was placed under the loading cell with 60% of weight (up to 1 kN) applied.…”

“…ALP enzymatic activity was quantified and qualified following previous method (Y. Liu et al, ; Miszuk et al, ; Q. Yao, Liu, Selvaratnam, Koodali, & Sun, ; Q. Yao, Liu, & Sun, ; Q. Yao et al, ). ALP staining images were taken via camera.…”

“…Quantitative gene expression analysis was carried out as we previously described (Y. Liu et al, ; Q. Yao, Liu, & Sun, ; Q. Yao et al, ) with some minor modifications. Briefly, total RNA was extracted using the GeneJET™ RNA Purification Kit (Thermo Scientific™, Waltham, Massachusetts).…”