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Title: To develop techniques that will enhance dermal cell and tissue attachment in order to create a seal and prevent infection of implant biomaterials used for ITAP
Author: Dowling, R. P.
ISNI:       0000 0004 5364 8898
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2015
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Failure modalities of bone anchoring and skin penetrating devices, such as Intraosseous Transcutaneous Amputation Prosthesis (ITAP), stem from the lack of dermal cell and tissue attachment at the skin implant interface. As a result the implant shaft offers a direct route for harmful pathogens into the body. The aim of my thesis is to develop techniques that will enhance dermal cell and tissue attachment, in order to create a tight biological seal of implant biomaterials currently used for ITAP. I compared the effects of fibronectin against its cell binding region- a 3-amino- acid region know as Arginine-Glycine-Aspartic Acid (RGD)- on human dermal fibroblast (HDF) attachment to ITAP substrates. Silanization of RGD- polypeptides provided a durable biological functionalisation technique that significantly increased HDF attachment compared with controls. No significant difference was observed between fibronectin and RGD-polypeptide functionalised substrates in vitro. I then investigated the effects of porosity (as a function of pore and strut diameter) on soft fibrosis tissue in-growth and vascularisation. Electron Beam Manufacturing (EBM) provided an effective method of creating precise 3- dimensional porous structures. Porosity as a function of pore and strut diameter led to optimal soft fibrosis tissue in-growth with 700μm pore and 300μm strut diameters exhibiting significantly increased vascularisation over other implants groups after 4 weeks in vivo. The development of these functionalisation techniques, which utilised porous structures and silanization of RGD sequences, were combined and applied to the ITAP device. An EBM porous flange, of 700μm pore and 300μm strut diameters, were silanised with RGD-polypeptide and compared with the current clinical standard ITAP device. Implants were tested in a trans-tibial, transcutaneous ovine model for 5-months. Functionalisation techniques employed in this study did not eradicate the failure modalities of ITAP devices, however they did not detrimentally affect the formation of a stable transcutaneous interface compared with current clinical standards. Significant positive effects were observed, with the biological functionalisation, using silanised RGD-polypeptides, significantly increasing dermal tissue infiltration and porous structures, manufactured by EBM, significantly increasing vascularisation. Functionalisation with silanised RGD-polypeptides to porous structures may provide an opportunity to enhance the skin implant interface and tight biological seal for bone anchoring and skin penetrating devices, such as ITAP, clinically.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available