Triethyl orthoformate covalently cross-linked chitosan-(poly vinyl) alcohol based biodegradable scaffolds with heparin-binding ability for promoting neovascularisation

Abstract

ReuseUnless indicated otherwise, fulltext items are protected by copyright with all rights reserved. The copyright exception in section 29 of the Copyright, Designs and Patents Act 1988 allows the making of a single copy solely for the purpose of non-commercial research or private study within the limits of fair dealing. The publisher or other rights-holder may allow further reproduction and re-use of this version -refer to the White Rose Research Online record for this item. Where records identify the publisher as the copyright holder, users can verify any specific terms of use on the publisher's website. TakedownIf you consider content in White Rose Research Online to be in breach of UK law, please notify us by emailing eprints@whiterose.ac.uk including the URL of the record and the reason for the withdrawal request. AbstractThere is a need to develop pro-angiogenic biomaterials to promote wound healing and to assist in regenerative medicine. To this end, various growth factors have been exploited which have the potential to promote angiogenesis. However these are generally expensive and labile which limits their effectiveness. An alternative approach is to immobilize heparin onto biocompatible degradable hydrogels. The heparin in turn will then bind endogenous proangiogenic growth factors to induce formation of new blood vessels.In this study we continue our development of hydrogels for wound healing purposes by exploring covalently cross-linking chitosan (CS) and polyvinyl alcohol (PVA) hydrogels using triethyl orthoformate (TEOF) .Two concentrations of TEOF ( 4 and 16 %) were compared for their effects on the structure of hydrogels -their swelling, pore size and rate of degradation and 2 for their ability to support the growth of cells and for their heparin binding capacity and their effects on angiogenesis in a chick chorioantoic membrane assay .Hydrogels formed with 4 or 16% both TEOF cross-linker were equally cyto-compatible.Hydrogels formed with 4% TEOF absorbed slightly more water than those made with 16%TEOF and broke down slightly faster than non-cross-linked hydrogels. When soaked in heparin the hydrogel formed with 16% TEOF showed more blood vessel formation in the CAM assay than that formed with 4% TEOF.

Heparinized Chitosan/hydroxyapatite Scaffolds Stimulate Angiogenesis in CAM Assay: Future Proangiogenic Materials to Promote Neovascularization to Accelerate Bone Regeneration

“…Chitosan was present on the top surface and the corresponding spectra showed a band for alkyl (CH 2 , CH 3 ) bending at 1375-1415 cm − 1 , a small hump between 1586 and 1650 cm − 1 corresponding to the CO stretching from Amide I, and, the peaks of CH 2 , CH 3 stretch near 2850-2915 cm − 1 24,41 . These spectra also showed a band between 1025-1060 cm − 1 assigned to C-O-C stretching and a broad peak at 3555 cm − 1 , which may be attributed to a combination of OH and NH, stretching vibrations 24,41 .…”

“…Regardless of the vast information available regarding the use of heparin to bind growth factors to scaffolds, not many studies regarding the angiogenic in uence of heparin itself on the bone healing process have been reported. Recently, our research group reported on the use of heparin loaded hydrogels as an angiogenic promoter for wound healing treatments [22][23][24] . On the other hand, Gümüşderelioğlu & Aday (2011) reported the osteogenic activity of heparinised chitosan scaffolds promoting in vitro proliferation and differentiation of pre-osteoblasts cells 25 .…”

Exploration of 2-Deoxy-D-Ribose and 17β-Estradiol as Alternatives to Exogenous VEGF to Promote Angiogenesis in Tissue-Engineered Constructs

“…It also regulates their stability and biological activity as well as long-term stimulation of endothelial cells [22 24]. Our group has explored the approach of using heparin bound to biomaterials to deliver VEGF using a layerby-layer method for coating scaffolds with heparin and then binding VEGF [25] and we have also reported on chitosan-based hydrogels for binding heparin [26,27]. However, binding VEGF with heparin is a long process and requires multistep actions to introduce VEGF with the TE scaffolds.…”

In-Situ Forming pH and Thermosensitive Injectable Hydrogels to Stimulate Angiogenesis: Potential Candidates for Fast Bone Regeneration Applications

“…Recently in our group, heparin was exploited to induce angiogenesis investigated via CAM assay to evaluate the potential attachment of physiologically available angiogenic growth factors to pro-angiogenic receptors by using heparin bonded chemically crosslinked chitosan poly-vinyl alcohol (PVA) hydrogels. Triethyl orthoformate (TEOF) crosslinked and heparin bonded hydrogels led to more blood vessel generation as compared to heparin-free control samples [62]. In addition, direct mixing of heparin in chitosan-PVA-PCL hydrogels in the absence of any growth factors was investigated for angiogenesis on chick embryo's CAM tissues for wound healing application.…”