Date of Award

August 2020

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Bioengineering

Committee Member

Melinda K Harman

Committee Member

B.Todd Heniford

Committee Member

Martin W King

Committee Member

Jiro Nagatomi

Committee Member

Alexey Vertegel

Abstract

In use since the 1960s, polypropylene (PP) biomaterials are common in commercially available hernia meshes due to their high tensile strength, good flexibility, and chemical resistance. The in vivo environment is highly variable, exposing mesh implants to oxidizing species and mechanical strains caused by normal healing, tissue integration, and the immediate and chronic inflammatory responses. As a result, changes in mesh implant materials can occur in vivo, including morphological changes, chemical changes and mechanical changes. The broad objective of this dissertation was to explore mechanisms of material changes in polymeric mesh implants after in vivo exposure using experimental characterization and biological assessments.

Biological assessments included mesh implants retrieved from patients after hernia repair surgery (mesh explants) to explore potential degradation mechanisms, specifically the impact of clinical characteristics for triggering material changes in pore size, surface chemistry, crystallinity and stiffness consistent with PP degradation. Development of an automated photogrammetric pore size and pore pattern recognition technique provided quantitative measurements of mesh pore size reduction and mesh contraction in mesh explants. Mesh class (pore size) was a factor affecting material changes in normalized crystallinity and reduced stiffness was observed in mesh explants from patients with infection.

Experimental characterization included two studies. In vitro simulated PP mesh degradation explored specific mechanisms that potentially contributed to PP material changes. The synergistic effect of reactive oxygen species (ROS) associated with chronic inflammation/infection and mechanical strains on PP mesh degradation was experimentally simulated. PP mesh degradation was observed in simulated ROS solutions made of 1.63M hydrogen peroxide (H2O2)/ 0.05M cobalt chloride (CoCl2), but the synergistic effect was not observed in the same simulated ROS solutions with applied low mechanical strains. A second experimental characterization involved surface modification of polymeric mesh implants for improved hernia mesh fixation with a hydrogel adhesive, called a “bio-adhesive mesh fixation system”. The “bio-adhesive mesh fixation system” combined two patented technologies of poly-glycidyl methacrylate/human serum albumin (PGMA/HSA) grafting and a poloxamine hydrogel adhesive. Its experimental maximum adhesive strength was approximately 2 times higher than that of unmodified mesh, which was achieved by mechanical interlock of the hydrogel tissue adhesive into the PP mesh pores and chemical bonding of the grafted albumin.

Mesh explants retrieved from patients were valuable resources to explore material changes and the degradation mechanisms in highly variable in vivo conditions. Assessments of mesh explants were challenging due to the unknown mesh material properties before implantation and the uncontrolled nature of patient variables inherent in retrieval analysis. Compared to biological assessments, experimental characterization for in vitro simulation and mesh fixation system contributed to understanding mesh behavior in a controlled condition and building the foundation for predicting mesh behavior in physiological conditions.

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