Novel chitosan derivative based composite scaffolds with enhanced angiogenesis; potential candidates for healing chronic
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TISSUE ENGINEERING CONSTRUCTS AND CELL SUBSTRATES Original Research
Novel chitosan derivative based composite scaffolds with enhanced angiogenesis; potential candidates for healing chronic non-healing wounds Muhammad Rizwan1 Rosiyah Yahya1 Aziz Hassan1 Muhammad Yar2 Adyani Azizah Abd Halim3 Anis Rageh Al-Maleki4 Lubna Shahzadi2 Waliya Zubairi2 ●
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Received: 25 November 2018 / Accepted: 25 May 2019 / Published online: 11 June 2019 © Springer Science+Business Media, LLC, part of Springer Nature 2019
Abstract The success of wound healing depends upon the proper growth of vascular system in time in the damaged tissues. Poor blood supply to wounded tissues or tissue engineered grafts leads to the failure of wound healing or rejection of grafts. In present paper, we report the synthesis of novel organosoluble and pro-angiogenic chitosan derivative (CSD) by the reaction of chitosan with 1,3-dimethylbarbituric acid and triethylorthoformate (TEOF). The synthesized material was characterized by FTIR and 13CNMR to confirm the incorporated functional groups and new covalent connectivities. Biodegradability of the synthesized chitosan derivative was tested in the presence of lysozyme and was found to be comparable with CS. The cytotoxicity and apoptosis effect of new derivative was determined against gastric adenocarcinoma (AGS) cells and was found to be non-toxic. The CSD was found to be soluble in majority of organic solvents. It was blended with polycaprolactone (PCL) to form composite scaffolds. From an ex ovo CAM assay, it was noted that CSD stimulated the angiogenesis. Graphical Abstract
* Rosiyah Yahya [email protected] 1
2
Department of Chemistry, Universiti Malaya, 50603 Kuala Lumpur, Malaysia Interdisciplinary Research Center in Biomedical Materials,
COMSATS University, Lahore 54000, Pakistan 3
Department of Oral and Craniofacial Sciences, Faculty of Dentistry, Universiti Malaya, 50603 Kuala Lumpur, Malaysia
4
Department of Medical Microbiology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia
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1 Introduction In all healthy tissues, a well grown blood vascular system is required for the diffusional exchange of nutrients and metabolites. The healing of wounded tissues also depends upon the extent and growth of vascular system surrounding it. The process of growing blood vessels from the existing ones is known as angiogenesis which plays a vital role for the integration of implanted scaffolds with the existing tissue [1]. The presence of healthier blood vascular system is essential for wound healing as it transports the cells, growth factors, micronutrients, oxygen and other required drugs to the wounded or implanted tissue which accelerates the healing process. The tissue engineered grafts/implants usually fail due to lack of neovascularization in the surrounding tissues which is a major problem in the field. The wounded tissues which lack in angiogenesis leads to poor blood supply and consequently chronic unhealed wound
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