Sustained presentation of BMP‐2 enhances osteogenic differentiation of human adipose‐derived stem cells in gelatin hydrogels

Abstract

Human adipose-derived stem cells (hASCs) show great potential for healing bone defects. Bone morphogenetic protein-2 (BMP-2) has been reported to stimulate their osteogenic differentiation both in vitro and in vivo. Here, methacrylated gelatin (GelMA) hydrogels were evaluated as a system to deliver BMP-2 to encapsulated hASCs from two different donors, and BMP-2 delivered from the hydrogels was compared to BMP-2 presented exogenously in culture media. GelMA hydrogels were shown to provide sustained, localized presentation of BMP-2 due to electrostatic interactions between the growth factor and biomaterial after an initial burst release. Both donors exhibited similar responses to the loaded and exogenous growth factor; BMP-2 from the hydrogels had a statistically significant effect on hASC osteogenic differentiation compared to exogenous BMP-2. Expression of alkaline phosphatase was accelerated, and cells in hydrogels with loaded BMP-2 deposited more calcium at one, two, and four weeks than cells without BMP-2 or with the growth factor presented in the media. There were no statistically significant differences in calcium content between groups with 25, 50, or 100 µg/mL loaded BMP-2, suggesting that using a lower growth factor dose may be as effective as a higher loading amount in this system. Taken together, these findings suggest that controlled delivery of BMP-2 from the GelMA enhances its osteogenic bioactivity compared to free growth factor presented in the media. Thus, the GelMA system is a promising biomaterial for BMP-2-mediated hASC osteogenesis. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1387-1397, 2016.

Synergistic Effects of Vascular Endothelial Growth Factor on Bone Morphogenetic Proteins Induced Bone Formation In Vivo: Influencing Factors and Future Research Directions

“…Although some authors reported that fast release of BMP2 might induce more ectopic bone regeneration than its sustained release [13], more papers confirmed that the sustained delivery strategy would prolong its activity and reduce its potential side effects [7, 43, 97–101]. …”

Effect of gel porosity and stiffness on culture of HepG2 cells encapsulated in gelatin methacrylate hydrogels

“…The cells in constructs are either cultured prior to implantation or directly implanted and allowed to grow in vivo post-implantation (Bhatia & Chen, 1999).It has been reported that the development of tissue within gel matrix is modulated by surface chemistry of the scaffold, its pore size, structure and mechanical properties, though gold standard of parameters has not been defi ned yet (Basu, 2004). Hollister et al have explained the requirement to modulate physical properties of gel matrix so as to suit the intended application (2002).A biodegradable, architecturally fl exible, photocrosslinkable and biocompatible gel has been synthesized from methacrylated gelatin gel GelMA (Van Den Bulcke et al, 2000) and has been exploited for cell culture studies by various groups (Chen et al, 2012;Nichol et al, 2010;Nikkah et al, 2012;Samorezov et al, 2016).…”

The Use of Adipose Tissue-Derived Progenitors in Bone Tissue Engineering - a Review

“…Moreover, lower dose of BMP-2 had a striking effect [28]. Co-expression of BMP-2 and Runx2 in ADSCs caused significantly increased bone regeneration [29].…”