Biosynthetic Corneal Implants for Replacement of Pathologic Corneal Tissue: Performance in a Controlled Rabbit Alkali Burn Model

Biosynthetic Corneal Implants for Replacement of Pathologic Corneal Tissue: Performance in a Controlled Rabbit Alkali Burn Model
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DOI:
10.1167/iovs.10-5224
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发表时间:
2011-02-01
影响因子:
4.4
通讯作者:
Fagerholm, Per
Fagerholm, Per
中科院分区:
医学2区
文献类型:
--
作者:
Hackett, Joanne M.;Lagali, Neil;Fagerholm, Per

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目的。目的评价结构增强、稳定的重组人胶原-磷脂酰胆碱(RHCIII-MPC)水凝胶作为角膜替代物在兔严重角膜损伤模型中的作用。4只角膜植入RHCIII-MPC水凝胶。其他8个对照角膜植入同种异体角膜或简单的交联型RHCIII水凝胶。所有病例均行前板层角膜移植,植入直径6.25 mm、厚350µm的纽扣,以替代受损的角膜组织。术后9个月行临床检查和活体共聚焦显微镜检查,术后取出植入物进行组织病理学和超微结构检查。结果:1例碱暴露导致角膜中央广泛瘢痕形成、眼表不规则和新生血管形成。术后4周,所有种植体均显示上皮完全覆盖,但6例伴有缝合诱导的血管形成。同种异体和RHCIII-MPC植入物均可再生稳定的复层上皮,并可见基底神经再生。最初,随着基质混浊的消退和基质胶原的重塑,脱细胞生物合成植入物中填充了宿主来源的角膜基质细胞。值得注意的是,RHCIII-MPC植入物在支持内源性细胞和神经再生的同时显示出对血管植入的抵抗。结论:基于RHC的生物合成植入物促进了碱烧伤兔眼的细胞和神经再生。在RHCIII-MPC植入物中,有证据表明对新生血管的抵抗力增强。(投资眼科VS科学。2011年;52:651-657)doi:10.1167/iovs.10-5224
PURPOSE. To evaluate the performance of structurally reinforced, stabilized recombinant human collagen-phosphorylcholine (RHCIII-MPC) hydrogels as corneal substitutes in a rabbit model of severe corneal damage.METHODS. One eye each of 12 rabbits received a deep corneal alkali wound. Four corneas were implanted with RHCIII-MPC hydrogels. The other eight control corneas were implanted with either allografts or a simple cross-linked RHCIII hydrogel. In all cases, 6.25 mm diameter, 350 mu m thick buttons were implanted by anterior lamellar keratoplasty to replace damaged corneal tissue. Implants were followed for nine months by clinical examination and in vivo confocal microscopy, after which implanted corneas were removed and processed for histopathological and ultrastructural examination.RESULTS. Alkali exposure induced extensive central corneal scarring, ocular surface irregularity, and neovascularization in one case. All implants showed complete epithelial coverage by four weeks postoperative, but with accompanying suture-induced vascularization in 6 out of 12 cases. A stable, stratified epithelium with hemidesmosomal adhesion complexes regenerated over all implants, and subbasal nerve regeneration was observed in allograft and RHCIII-MPC implants. Initially acellular biosynthetic implants were populated with host-derived keratocytes as stromal haze subsided and stromal collagen was remodeled. Notably, RHCIII-MPC implants exhibited resistance to vascular ingrowth while supporting endogenous cell and nerve repopulation.CONCLUSIONS. Biosynthetic implants based on RHC promoted cell and nerve repopulation in alkali burned rabbit eyes. In RHCIII-MPC implants, evidence of an enhanced resistance to neovascularization was additionally noted. (Invest Ophthalmol Vis Sci. 2011;52:651-657) DOI:10.1167/iovs.10-5224