Novel Injectable Interpenetrating Polymer Network as a Semi-Permanent Injectable Implant for Soft Tissue Augmentation - eScholarship

Author(s): Leung, Joanne C. | Advisor(s): Wu, Ben M; Rodriguez, Larissa V | Abstract: Injectable fillers have been widely used for soft tissue augmentation in cosmetic procedures, as well as minimally invasive treatment for medical conditions such as urinary and fecal incontinence, vesicoureteral reflux and vocal cord repair. The market for injectable fillers is a multibillion dollar industry worldwide, and each FDA-approved injectable filler has its own drawbacks, namely, lack of durability for temporary fillers, and difficulty in injection for semi-permanent to permanent fillers. A new material that offers solutions to the problems with the existing products will have a big market potential. The intended application of the novel filler in this study is for treating urinary incontinence. In this thesis, we present a novel injectable filler that lasts g 6 months, is easy to inject, has an elastic modulus that matches the soft tissue to fit the contour, has customizable mechanical characteristics for different application, off-the-shelf, has good biocompatibility, and the feasibility to be co-injected with cells. The novel injectable semi-permanent filler designed in this study is a hydrogel composed of an interpenetrating polymer network (IPN) of random co-pHEMA-PEGMA-TEGDMA intertwined with CMC chains with various degrees of entanglement, polymer chain lengths, crosslinking and different flow properties. We name this injectable HPTC.HPTC was found to have the desirable injectability as a soft tissue filler only under a narrow range of optimal conditions. We studied the parameters that govern the injectability of HPTC using Intron injectability assay and rheological testing. We characterized the factors that were important for determining its force of injection, elastic and viscous moduli, oscillatory stress in response to increasing strain, viscosity change under constant shearing, and the percentage loss in elastic modulus after disruptive shearing. The effect of water content, steric hindrance introduced by the CMC pre-polymerization, CMC chain length, and the percentage of TEGDMA all have important contribution to the injectability of HPTC. We showed that optimal HPTC has superior injectability over the major permanent fillers that are FDA approved, which solved the needle-clogging problem.HPTC also showed good biocompatibility with no signs of fibrotic capsules, durability in vivo for 6 months, good tissue integration, undetectable migration to other organs, and feasibility to be co-injected with cells. It has also been evaluated for its efficacy in the treatment of urinary incontinence in an animal model for 24 weeks, and has shown significant dose-dependent improvement in urethral function by having an increased abdominal leak point pressure (ALPP) compared to the incontinence model alone. Combining its superior injectability, customizable mechanical viscoelastic properties, biocompatibility and effectiveness of restoring the urethral function in a rat incontinence model for 6 months, HPTC is a good candidate as a semi-permanent/ permanent injectable material for soft tissue augmentation.