Traditional methods for dermal wound closure such as sutures and staples are invasive and can result in soft tissue trauma, increasing the likelihood of localized inflammation and infections. Alternately, while tissue adhesive alternatives can effectively seal and adhere to the wounds, they can also present safety concerns relating to immunogenic responses and tissue toxicity. Herein, we fabricate injectable, adhesive, and cytocompatible poly(oligo(ethylene glycol) methyl ether methacrylate) (POEGMA)-dopamine (DA) hydrogels co-crosslinked via hydrazone and self-polymerized dopamine crosslinks that exhibit high water retention, improved tissue adhesiveness, and effective tissue regeneration properties. POEGMA-DA hydrogels exhibit independently tunable gelation properties based on their dual crosslinking mechanism, allowing for gelation as fast as 24 s (allowing for injection and rapid filling of irregularly-shaped wounds) while achieving relevant compressive moduli of up to 37 kPa and in vitro skin adhesion strengths of up to 1.2 kPa. The POEGMA-DA hydrogels induced no significant inflammation while demonstrating high interfacial adhesiveness in a stented skin excisional mouse model, enabling efficient dermal tissue regeneration by supporting collagen remodelling and enabling the regeneration of hair follicles, sebaceous glands, and blood vessels at the excision site over the 14-day study timeline. As such, injectable POEGMA-DA hydrogels represent a relevant non-toxic and adhesive alternative wound closure system for treating deep dermal wounds. / Thesis / Master of Applied Science (MASc) / Effective wound healing and subsequent tissue regeneration after a physical injury requires a moist sterile environment, the presence of oxygen, nutrients and enzymes, an efficient blood supply to the wound site, and a controlled inflammatory response to initiate the healing process. External methods of closing the wound to prevent infection aid in faster healing like sutures, staples, and liquid sealants which can result in infections and/or the stimulation of an inflammatory response that can hinder tissue restoration. Hydrogels, water-swellable polymer networks, represent an alternative solution that can both suppress infection while simultaneously promoting wound healing. Hydrogels have a similar structure to soft tissues like skin and can thus provide a supportive environment for cells to promote tissue regeneration and restore tissue structure and function. The swelling of hydrogels in water is highly beneficial for providing moisture at the wound site; however, this high degree of water retention also means they have a hard time sticking to tissues. To address this challenge, hydrogels can be modified with a component naturally derived from marine mussels that allows them to stick to their wet habitats, helping hydrogels to stick to the wound site while healing. In this thesis, mussel-inspired hydrogels are designed and can spontaneously gel and stick to a wound site to accelerate the restoration of the structure and function of skin. These biodegradable and injectable hydrogels are effective in accelerating wound closure with minimal evidence of scarring while suppressing negative inflammatory reactions and restoring the structure of skin by promoting the regeneration of hair follicles, sebaceous glands and blood vessels.
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/29067 |
| Date | January 2023 |
| Creators | Randhawa, Gurpreet K |
| Contributors | Hoare, Todd, Chemical Engineering |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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