File(s) under embargo
Reason: publisher request
until file(s) become available
Therapeutic Methacrylic Monomers and Functional Graphenic Materials as Bioactive Additives to Medical Adhesives
thesisposted on 29.10.2020, 16:42 by Zoe Wright
Medical adhesives such as quick-cure skin glues and bone cements provide rapid, custom tissue fixation and excellent distribution of mechanical stress around injured tissue, often in conjunction with other fixation methods like stitches and metallic orthopedic implants. The role that medical adhesives play in healing is primarily a passive one, preventing further damage and enabling the body to respond to injury naturally – but these materials have much greater potential. Because of their placement directly at the site of injury, medical adhesives are in a prime position to provide the body with cues that can actively guide and improve tissue regeneration. However, the features that make medical adhesives strong and convenient also make these materials challenging platforms for such biological activity. Additives that aim to install bioactivity into medical adhesives can easily interfere with the factors that make these adhesives mechanically strong, such as: bulk homogeneity, sufficient in situ chemical transformation to achieve cure, polymer chain entanglements, and limited swelling in biological environments. If the tradeoff between bioactivity and mechanical strength could be addressed, the capabilities of bioactive adhesives could be dramatically expanded.
The following body of work explores several strategies for incorporating bioactivity into medical adhesives without sacrificing bulk mechanical strength. In particular, novel therapeutic methacrylic (TMA) monomers are reported that provide a platform for controlled, local release of small molecule drugs from a range of medical adhesive matrices. Covalent conjugation of the drug payload to a methacrylic backbone by a hydrolysable tether bond provides not only a new mechanism of controlling the profile of drug release (via the reactivity of the tether bond), but also: greater miscibility of the drug in the adhesive matrix, resulting in decreased phase separation; increased drug delivery efficiency relative to adhesives in which the same drug is incorporated by simple admixing; and significantly improved mechanical strength that is retained even after drug delivery. TMA monomers have been explored as additives capable of delivering pain management drugs from both skin adhesives (Chapter 2) and bone cement (Chapter 3). In addition to the strategy of hydrolysis-controlled drug release, functional graphenic materials (FGMs) that carry and release osteogenic ions have been explored as bioactive additives to bone cements (Chapter 4). In this strategy, the FGMs provide bioactivity, while alterations to the formulation of the bone cement matrix, informed by the chemical structure of the FGMs, are used to mitigate changes to the mechanical integrity of the cement.
- Doctor of Philosophy (PhD)