(M1330-12-81) Development of Nanofiber-Based, Anti-proliferative Sutures for Glaucoma Surgery

Purpose: Drug-eluting sutures present a compelling opportunity to improve outcomes across a wide range of surgical procedures by providing local, sustained drug delivery within the existing surgical paradigm (1). Glaucoma surgery is designed to reduce intraocular pressure (IOP) by venting aqueous humor to reduce the risk of vision loss; however, post-operative fibrosis is a major cause of complications and failure, which leads to suboptimal IOP lowering. Adjunctive anti-proliferative agents are cytotoxic and are not effective for the duration of the wound healing period. Here, we engineered nanofiber-based sutures to sustain delivery of a broadly used anti-proliferative agent, rapamycin, at the surgical site to inhibit TGF-β induced fibroblast proliferation (2,3). Rapamycin-eluting sutures significantly reduced IOP and extended bleb survival in a rabbit model of glaucoma surgery without modifying the surgical workflow.

Methods: Electrospinning was utilized to generate nanofibers consisting of poly(L-lactide), polyethylene glycol, and different percentages (20%, 40%, and 80% w/w) of rapamycin. These nanofibers were twisted around 10-0 nylon sutures until the overall diameter was appropriate for use as 8-0 sutures (40-49 µm). Rapamycin-eluting sutures were assessed for their morphology through scanning electron microscopy (SEM), breaking strength, and in vitro drug release. Rapamycin-eluting suture efficacy was evaluated in a trabeculectomy model in normotensive New Zealand White rabbits.

Results: SEM analysis demonstrated consistent coating of nanofibers around the nylon suture core, resulting in an overall suture diameter of 48.2 ± 0.2 µm (n=4). The breaking strength of the sutures exceeded the clinical requirements (0.39 N) for 8-0 sutures by 30%. In vitro drug release studies revealed sustained release of rapamycin from 20% and 40% nanofiber formulations for a minimum of 14 days (Figure 1A). Evaluation in a rabbit model of glaucoma surgery showed that 40% rapamycin-eluting sutures, placed beneath the conjunctival closure, significantly reduced IOP (Figure 1B) and prolonged the survival of blebs in normotensive rabbits compared to conventional nylon sutures (n=3, each). These findings suggest that modulating the scarring process via continuous delivery of an anti-proliferative agent can significantly improve surgical outcomes (Figure 1C).

Conclusion: Nanofiber-coated, rapamycin-eluting sutures met suture diameter and strength specifications, and provided sustained delivery of rapamycin, resulting in IOP reduction and extended bleb survival compared to conventional surgery methods. This promising approach has the potential to reduce complications and enhance surgical outcomes in glaucoma surgery.

References: (1) Parikh KS, Omiadze R, Josyula A. Bioeng Transl Med. 2021: 6: e10204
(2) Parikh KS, Josyula A, Inoue T, Journal of Controlled Release. 2023: 353: 96-104
(3) Shaodan Zhang, Lin Du, Di Wu, Chi Liu, Hailin Wang; Invest. Ophthalmol. Vis. Sci. 2017: 58(8):4948

Acknowledgements: This work was supported by Robert H. Smith Family Foundation, NSF (BGE-1232825), NIH (R01HL141612), and a departmental grant to the Wilmer Eye Institute from Research to Prevent Blindness.

Figure 1. Trabeculectomy procedures were performed in normotensive rabbits using either nylon (n=3) or rapamycin (Rap-eluting) nanofiber-coated (n=3) sutures. (A) Nanofiber-based sutures demonstrated tunable release of rapamycin in vitro. (B) 40% Rap-eluting sutures significantly decreased IOP in comparison to nylon sutures (p < 0.05) due to decreased scarring in the channel and improved fluid drainage from the eye. (C) The fluid pockets, or blebs, that form as fluid drains from an open channel remained functional for longer in rabbits with 40% Rap-eluting sutures, confirming that scarring and subsequent closing of the channel was delayed.