Dissertations and Theses

Date of Award

2026

Document Type

Dissertation

Department

Biomedical Engineering

First Advisor

Steven B. Nicoll

Second Advisor

Mitchell B. Schaffler

Third Advisor

Sihong Wang

Keywords

Hydrogel, Adhesive, Emulsion, Biomaterial, Bulking

Abstract

Soft tissue filling materials are most commonly associated with various aesthetic, cosmetic procedures, primarily using lightly cross-linked hyaluronic acid to fill wrinkles and give facial features a more youthful appearance. These natural materials are biocompatible but degrade over time while more persistent synthetic fillers may provoke a chronic inflammatory response. Migration from the injection site is also a key factor as this may not only render the implant non- functional but necessitate further procedures for removal of the foreign material. Such concerns are more pronounced for soft tissue reconstruction procedures (e.g., to treat congenital defects or traumatic injuries), which require implant longevity and retention at the injection site. The addition of an adhesive component to the material may reduce migration but this is complicated by the ubiquitous presence of water in a biological environment, which can both disrupt the chemistry of the adhesive as well as act as a physical barrier to the substrate. Hence, there is a need for a long-term, soft tissue bulking material that is able to achieve adhesion in a hydrated environment. Cellulose is the most abundant biopolymer on Earth and its derivatives have been approved by the FDA for use in a multitude of food, cosmetic, and biomedical products. Methylcellulose (MC), an amphiphilic cellulose derivative, may be methacrylated to produce injectable, redox-polymerized hydrogels that can form covalently bonded, long-lasting soft implants in situ. Carboxymethylcellulose can be oxidized via periodate treatment (oCMC) to impart adhesivity through the production of aldehyde functional groups, which form imine bonds with the primary amines of proteins via Schiff base reactions. These two polymers may be combined to engineer a semi-interpenetrating polymer network hydrogel (MoCMC) that is capable of adhesion to tissue, but the hydrophilic nature of carboxymethylcellulose, owed to its inherent anionic charge, leads to sequestration of water and a reduction in adhesive and mechanical strength. To combat these drawbacks, the MoCMC adhesive was reformulated with the addition of a calcium chloride solvent and natural plant-based oil to form an emulsion. The free calcium dications enable ionic crosslinking between carboxymethylcellulose chains, strengthening the semi-interpenetrating polymer network. The oil forms a multitude of micron-sized droplets interspersed throughout the gel network, emulsified by the methylcellulose, that serve to disperse moisture from the surface of the gel. The addition of both components was shown to restore the material’s adhesive strength lost in the presence of moisture and enhance its mechanical properties. The presence of the oxidized polymer was not found to be cytotoxic, however, the proliferation of human dermal fibroblasts was arrested in co-culture. Despite this, animal experiments revealed no adverse effects following subcutaneous injection in rodents over the course of 12 weeks. These experiments demonstrate that MoCMC is a safe, minimally invasive soft tissue filling material that may be appropriate for long-term use in vivo. The novel addition of oil in the form of an emulsion hydrogel further improves its adhesive properties, making it suitable for more demanding soft tissue reconstructive procedures.

Available for download on Thursday, June 25, 2026

Included in

Biomaterials Commons

Share

COinS