Collagen-Based Artificial Corneal Scaffold with Anti-Infective Capability for Prevention of Perioperative Bacterial Infections

Bacterial infection following implantation of an artificial corneal scaffold is a serious complication. Conventional antibiotic prophylaxis, which includes topical vancomycin application, is limited by low bioavailability, high dosing requirement, and poor patient compliance. The ideal option to overcome these issues is an antibiotic-eluting corneal prosthesis that sustains the local release of drug. In this study, we incorporated vancomycin in thick 15% collagen hydrogels to create an artificial corneal scaffold with anti infective capability. The incorporation of vancomycin did not significantly alter the Young's modulus, transparency and refractive index of the vancomycin-loaded hydrogel (VH), which were 0.79 +/- 0.04 MPa (p = 0.233 compared to blank hydrogel), 94.3 +/- 2.3% (p = 0.115) and 1.346 +/- 0.005 (p = 0.264), respectively. In vitro, the drug elution was sustained for up to 7 days. The VH was subsequently implanted intrastromally in rabbit corneas, replacing stromal tissue that was removed following femtosecond laser-assisted small incision lenticule extraction procedure. In vivo, the vancomcyin could be detected in the aqueous humor for up to 10 days. We then created a corneal infectious keratitis model by intrastromal injection of 1 X 10(8) CFU/ml of Staphylococcus aureus inoculate on day 2 postimplantation. On day 3 postinfection, the VH-implanted corneas were clear and nonedematous and showed a substantial reduction of log 2.5 in S. aureus compared to the blank hydrogel-implanted corneas, which appeared hazy, edematous, and had excessive inflammation. Immunohistochemistry of inflammatory marker, CD18, demonstrated a significant reduction in inflammatory cells in VH-implanted corneas (49 +/- 9 cells/unit area) compared to blank hydrogel-implanted corneas (523 +/- 15 cells/unit area) (p < 0.001). In conclusion, we have demonstrated the efficacy of a drug-eluting corneal implant in preventing perioperative bacterial infections.