Improving the osteogenic potential of BMP-2 with hyaluronic acid hydrogel modified with integrin-specific fibronectin fragment

Item does not contain fulltextWhile human bone morphogenetic protein-2 (rhBMP-2) is a promising growth factor for bone regeneration, its clinical efficacy has recently shown to be below expectation. In order to improve the clinical translation of rhBMP-2, there exists strong motivation to engineer better delivery systems. Hyaluronic acid (HA) hydrogel is a suitable carrier for the delivery of rhBMP-2, but a major limitation of this scaffold is its low cell adhesive properties. In this study, we have determined whether covalent grafting of an integrin-specific ligands into HA hydrogel could improve cell attachment and further enhance the osteogenic potential of rhBMP-2. A structurally stabilized fibronectin (FN) fragment containing the major integrin-binding domain of full-length FN (FN III9*-10) was engineered, in order to be incorporated into HA hydrogel. Compared to non-functionalized HA hydrogel, HA-FN hydrogel remarkably improved the capacity of the material to support mesenchymal stem cell attachment and spreading. In an ectopic bone formation model in the rat, delivery of rhBMP-2 with HA-FN hydrogel resulted in the formation of twice as much bone with better organization of collagen fibers compared to delivering the growth factor in non-functionalized HA hydrogel. This engineered hydrogel carrier for rhBMP-2 can be relevant in clinical bone repair

Injectable In Situ Forming Hybrid Iron Oxide-Hyaluronic Acid Hydrogel for Magnetic Resonance Imaging and Drug Delivery

Contains fulltext : 149649.pdf (Publisher’s version ) (Closed access)The development of multimodal in situ cross-linkable hyaluronic acid nanogels hybridized with iron oxide nanoparticles is reported. Utilizing a chemoselective hydrazone coupling reaction, the nanogels are converted to a macroscopic hybrid hydrogel without any additional reagent. Hydrophobic cargos remain encapsulated in the hydrophobic domains of the hybrid hydrogel without leakage. However, hydrogel degradation with hyaluronidase liberates iron oxide nanoparticles. This allows the utilization of imaging agents as tracers of the hydrogel degradation. UV-vis spectrometry and MRI studies reveal that the degradability of the hydrogels correlates with their structure. The hydrogels presented here are very promising theranostic tools for hyaluronidase-mediated delivery of hydrophobic drugs, as well as imaging of hydrogel degradation and tracking of degradation products in vivo