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Title: Host response to tissue derived decellularised crosslinked biomaterials
Author: Ashwin, H. M.
ISNI:       0000 0004 6059 6969
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2016
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Tissue derived implants are used in a wide range of tissue repair applications. They can be sourced either from human donors (allograft) or from animals (xenograft), with harvest locations including dermis, small intestine submucosa and pericardium. To help reduce antigenicity and provide the desired characteristics of the implant, all these materials are processed. These manufacturing processes can include delipidation, decellularisation, crosslinking and sterilisation. Balancing host immune response to tissue derived implants is a critical component of wound healing, with excessive and inadequate interactions being detrimental to patient recovery and implant functionality. In these studies the effect of using 1,6 hexamethylene diisocyanate (HMDI) to impart varying levels of crosslinking to acellular porcine dermal collagen decellularised using the propriety Permacol™ process was assessed. HMDI is incorporated into the amino acid structure of collagen by reacting with the amine groups found on lysine and hydroxylysine side chains. Biophysical characterisation established the direct effect varying crosslinking levels present in the implants had on resistance to enzyme degradation, thermal stability and mechanical properties. Potential leukocyte activation was measured in vitro via reactive oxygen species (ROS) generation. Leukocytes are one of the first immune cell populations recruited to implantation sites, possessing formidable secretomes capable of significantly accelerating material degradation, particularly through extracellular release of ROS. In addition, subsets of the implants produced were implanted subcutaneously in a rat model to evaluate the host immune response in relation to the crosslinking level. The addition of HMDI crosslinks into acellular porcine dermal collagen decellularised using the propriety Permacol™ process was shown to increase resistance to enzyme degradation and thermal stability but had minimal effect in vitro on mechanical properties and ROS production. Low levels of HMDI crosslinking were required to impart resistance to enzyme degradation. In vivo low levels of HMDI crosslinks, such as those present in Permacol™ surgical implant, did not affect the host immune response. Higher levels of HMDI crosslinking in vivo was shown to delay the resolution of the host's immune response.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral