Grillo, Alessandra; (2022) A novel tissue engineering approach to develop a biomimetic frugal mesh for abdominal wall repair. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The aim of the study was to create a novel and frugal hybrid mesh for abdominal hernia repair. The hybrid mesh was composed of a synthetic component, represented by low-cost meshes (LCM) repurposed from mosquito meshes, to provide the adequate mechanical support to the host tissues, and a biomimetic element represented by collagen type I arranged in a highly aligned architecture to mimic the host tissues in the abdominal wall. LCM have been successfully used to surgically repair hernias in low-income countries achieving similar surgical outcomes to commercial meshes at a fraction of the cost. They could potentially be used in high-income countries but barriers such as little in vitro characterisation and type of sterilisation method used have prevented their widespread use. Therefore, we characterised LCM properties with and without Ethylene Oxide (EO) sterilisation, showing how ultrastructure and biocompatibility are not significantly affected by the process whilst mechanical properties were weakened by the EO sterilisation method, yet maintained their similarity with native rectus sheath. We developed a method for producing acellular sheets of aligned collagen combining confined horizontal shear flow and fluid removal through Real Architecture for 3D Tissues technique (RAFT), which resulted in high collagen and cellular alignment but weak mechanical properties. The anisotropic collagen component was then integrated with the EO sterilised LCM in an aligned hybrid mesh (AHM). In vitro tissue remodelling was evaluated through MMP production and novel collagen deposition, showing increased MMP production and increased aligned collagen deposition over 14 days. Moreover, hybrid meshes were cultured in a dynamic system to mimic abdominal pressure and evaluate the impact of tension applied on the hybrid constructs, showing a higher degree of alignment in both aligned and non-aligned hybrids. To conclude, this study provides information on the in vitro characteristics of LCM to promote their adoption to high income countries with a cost-effective solution and proposes the design of a novel anisotropic hybrid mesh for abdominal hernia repair, which could help to alleviate complications experienced by patients and reduce costs for healthcare systems worldwide.

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