title: Immunological responses in mice to full-thickness corneal grafts engineered from porcine collagen.
abstract: Tissue-engineered (TE) corneas were fabricated from porcine collagen cross-linked with 1-ethyl-3-(3-dimethyl aminoproplyl)carbodiimide (EDC) and N-hydroxysuccinimide (NHS), and were transplanted into BALB/c mice orthotopically using a full-thickness penetrating keratoplasty (PKP) procedure. The biocompatibility was evaluated by assessing both local and systemic immune responses. Myeloid cells including granulocytes and macrophages were the main infiltrating cells in recipient cornea and in retro-TE corneal membrane which developed 7-10 days post surgery. Sodium citrate was found to be effective in reducing fibrin accumulation in anterior chamber post grafting at early time points, but it did not prevent formation of the retro-TE corneal membrane. No significant T cell activation was observed in the submandibular draining lymph nodes (SMDLN) by flow cytometry. Anti-porcine type I collagen IgG antibodies were detected in the serum of grafted mice from 2 weeks post grafting and the concentration of antibodies increased with time. Overall, porcine collagen-EDC/NHS TE corneas were tolerated well in murine recipients, causing mainly a self-limiting local innate immune response and a low-grade humoral response with little evidence of sustained T cell activation. Retro-TE corneal membrane formation was the main complication and barrier to clarity.
authors.affiliation: Department of Ophthalmology, Institute of Medical Science, Foresterhill, University of Aberdeen, Aberdeen AB25 2ZD, Scotland, UK.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.forename: Lucia
authors.initials: L
authors.lastname: Kuffová
authors.forename: May
authors.initials: M
authors.lastname: Griffith
authors.forename: Zexu
authors.initials: Z
authors.lastname: Dang
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Muckersie
authors.forename: Yuwen
authors.initials: Y
authors.lastname: Liu
authors.forename: Christopher R
authors.initials: CR
authors.lastname: McLaughlin
authors.forename: John V
authors.initials: JV
authors.lastname: Forrester
mesh_terms: D000818:Animals; D024042:Collagen Type I / Q000008:administration & dosage* / Q000276:immunology* / Q000627:therapeutic use*; D016039:Corneal Transplantation / Q000276:immunology* / Q000295:instrumentation*; D019544:Equipment Failure Analysis; D006085:Graft Survival / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D019736:Prostheses and Implants; D011474:Prosthesis Design; D013552:Swine; D023822:Tissue Engineering / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D024042:Collagen Type I