Overview

This dissertation, Applications of Self-assembling Peptide Nanofibre Scaffold and Mesenchymal Stem Cell Graft in Surgery-induced Brain Injury by Ka-kit, Gilberto, Leung, 梁嘉傑, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Surgery-induced brain injury (SBI) refers to trauma caused by routine neurosurgical procedures that may result in post-operative complications and neurological deficits. Unlike accidental trauma, SBI is potentially subject to preemptive interventions at the time of surgery. SBI can cause bleeding, inflammation and the formation of tissue gaps. Conventional haemostatic techniques, though effective, are not necessarily conducive to healing. Inflammation and the absence of extracellular matrix in tissue gaps also hinder regeneration after SBI. This study investigated the applications of RADA16-I, a type I self-assembling peptide nanofibre scaffold (SAPNS), and mesenchymal stem cells (MSCs) in the treatment of SBI. Using animal SBI models, treatments were applied immediately and locally onto the operative fields, taking advantages of the haemostatic and cell-carrying properties of RADA16-I, the immune- modulatory effects of MSCs, and the earliest available therapeutic window for SBI. There were three objectives. Objective 1 was to compare RADA16-I with conventional haemostatic methods, including electrocautery and fibrin sealant, in their effects on the brain's acute cellular inflammatory response. The hypothesis was that RADA16-I would cause the same or a lesser degree of inflammation. This study showed that RADA16-I was superior to electrocautery, and was noninferior to conventional topical haemostats. Objective 2 was to study the in vitro expansion of MSCs within RADA16-I in preparation for in vivo transplantation. The hypothesis was that the in vitro survival of MSCs would vary between different RADA16-I concentrations and culturing methods. This study showed that plating MSCs onto pre-buffered RADA16-I would protect the cells against RADA16-I's intrinsic acidity and result in better initial survival. Subsequent integration with the RADA16-I hydrogel, however, was poor. Mixing the cells directly with RADA16-I caused initial cell loss but allowed better integration. RADA16-I at lower concentrations resulted in better survival but also more fragile hydrogels that were mechanically unfit for transplantation. Mixing MSCs with 0.5% RADA16-I for seven days represented a compromise between these competing factors. Objective 3 was to study the in vivo effects of a MSC-RADA16-I implant on tissue reactions after SBI. The hypothesis was that the combinatorial therapy would result in less cellular inflammatory response than MSC alone or RADA16-I alone. Implants of pre-buffered 0.5% RADA16-I hydrogel, with or without cells, were found to cause less inflammation than control. MSCs in free suspension resulted in significantly more pronounced inflammation than when carried in RADA16-I. Supplementing RADA16-I with MSCs, however, did not confer additional benefit over RADA16-I alone. The present study provided new preclinical evidence to support future clinical testing of RADA16-I as a novel surgical haemostat. It also demonstrated the feasibility of early intracerebral transplantation of RADA16-I hydrogel in the treatment of SBI. Whether RADA16-I and/or transplanted MSCs could modulate the brain's inflammatory response after SBI require further investigations, which may include the search for the optimal ex vivo expansion technique and specifically tailored nanofibre scaffold. The translational applications of these finding

Full Product Details

9781361347157

Table of Contents

Reviews

Author Information

Tab Content 6

Customer Reviews

Recent Reviews

Countries Available