Dexamethasone Delivery via Amphiphilic, Low-swelling Hydrogels Treats Postoperative Inflammation in Cervical Spine...

Anterior cervical spine surgeries are often complicated by difficulty swallowing due to local postoperative swelling, pain, scarring, and tissue dysfunction. These postoperative events lead to systemic steroid and narcotic use. Local, sustained drug delivery may address these problems, but current materials are unsafe for tight surgical spaces due to high biomaterial swelling, especially upon degradation. To address these shortcomings, a low-swelling, amphiphilic hydrogel system termed DexaPatch is developed containing dexamethasone-poly(lactic-co-glycolic acid) (PLGA) microparticles for sustained release upon local implantation in the surgical site. The bulk amphiphilic hydrogel, comprised of 4-arm poly(ethylene glycol) (PEG)-maleimide macromer cross-linked with triblock dithiolated PEG-poly(propylene glycol)-PEG (poloxamer a.k.a. Pluronic), achieves consistent and tunable mechanical and low-swelling properties. Dexamethasone is released in a burst, followed by a sustained release over 40 days, similar to the release from microparticles alone. The DexaPatch system is lyophilized for shelf stability and surgical handling properties, sterilized, and briefly rehydrated in the operating room prior to surgical implantation in a rabbit model of anterior spinal surgery. DexaPatch results in significantly reduced prevertebral edema radiographically and decreased fibrosis in prevertebral muscles compared to sham surgery. This implantable biomaterial platform reduces local postoperative inflammation with potential surgical applications throughout the body.