Abstract
Biomaterials designed to replace the diseased cornea could be used to treat corneal blindness where human donor tissue is in short supply, but challenges are the integration of biomaterials with host tissue and cells, avoiding a rapid material degradation and maintaining corneal transparency. Additionally, implantation surgery often triggers an aggressive wound healing response that can lead to corneal thinning and opacity. Here, we report a collagen-based hydrogel with transparency and mechanical properties suitable for replacing a substantial portion of a damaged or diseased corneal stroma. The porous hydrogel permitted migration and population by host cells while maintaining transparency and thickness six months after surgical implantation in an in vivo model of human corneal surgery. With a novel hybrid surgical implantation technique inspired by LASIK refractive surgery, rapid wound healing occurred around implants to maintain biomaterial integrity, transparency and function. Host stromal cell repopulation and regeneration of host epithelium and nerves were observed, as necessary steps towards corneal regeneration. Finally, as a proof-of-principle, the hydrogel loaded with a neuroregenerative drug achieved sustained slow-release drug delivery in vitro. The proposed hydrogel and novel implantation technique together represent a therapeutic approach with translational potential for replacing and regenerating diseased corneal stromal tissue.
Highlights
Biomaterials designed to replace the diseased cornea could be used to treat corneal blindness where human donor tissue is in short supply, but challenges are the integration of biomaterials with host tissue and cells, avoiding a rapid material degradation and maintaining corneal transparency
Optical transmission in vitro was equivalent or superior to the human donor cornea stored in standard DMEM for each tested wavelength, with average bioengineered porcine collagen (BPC) transmission of about 90% in the visible wavelength range (Fig. 1c)
We have previously reported the mechanical properties of the BPC material relative to the healthy human donor c ornea[12]
Summary
Biomaterials designed to replace the diseased cornea could be used to treat corneal blindness where human donor tissue is in short supply, but challenges are the integration of biomaterials with host tissue and cells, avoiding a rapid material degradation and maintaining corneal transparency. Conventional full-thickness corneal transplantation (penetrating keratoplasty) has long been the standard method of corneal replacement, but recently this technique has been complemented by newer methods selectively replacing a specific corneal layer These so-called lamellar keratoplasty techniques have the advantage of being less invasive, as only the diseased part of the cornea is replaced while leaving the surrounding healthy tissue intact. In cases where the indication for vision-restoring surgery is corneal stromal pathology such as keratoconus, corneal scarring or dystrophies, the least invasive procedure is to replace only the affected stromal tissue[3] Approaches such as re-use of donor-derived refractive surgical stromal lenticules (obtained using smallincision lenticule extraction, or SMILE) to treat stromal disease such as keratoconus[7] or corneal p erforation[8] are gaining popularity, the human donor-sourced material is still scarce, and is only available in limited thickness and diameter. Host cells did not appear to repopulate the implanted material to induce a stromal regenerative response[3,11], while corneal nerve regeneration, critical for wound healing and long-term corneal homeostasis, was achieved to the extent expected following standard transplantation but not to normal levels[11]
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