Tej Kohli: Bioengineered Cornea Are About To Enter The Clinical Realm. What Does That Mean?

Gross appearance of the regenerated cornea of all 10 patients who received bioengineered corneal implants comprising recombinant human collagen. Left two columns: patients at 2 years post-operation. Right two columns: The same patients at 4 years post-surgery. Compiled figures adapted from Fagerholm et al. (2010, 2014), with permission from AAAS and Elsevier.

Background

What Is The Cornea?

How Many People In The World Are Blind?

What Is Corneal Transplantation?

The Limitations Of Human-Donated Cornea

Can Bioengineered Cornea Plug The Treatment Gap?

Bioengineered Corneal Epithelium

A CLET implant performed in Canada using a fibrin substrate (Le-Bel et al. 2019). More recently, a simple limbal epithelial transplantation (SLET) has been developed which bypasses the need for expansion of stem cells in expensive cleanrooms (Sangwan et al. 2012). Preparation of a corneal epithelial limbal graft, showing the steps. (a) Limbal biopsy from the patient’s contralateral eye; bar: 1 mm. (b) expansion by co-culturing with irradiated human dermal fibroblasts; bar: 200 μm. © Cells on fibrin. (d) Histology (Masson’s Trichrome staining) of the tissue-engineered epithelium, showing a differentiated epithelium on a fibrin substrate; bar: 10 μm. Reproduced from Le-Bel et al. (2019) with permission from Elsevier.

Bioengineered Corneal Stroma

Using support structure to facilitate the printing of a corneal structure with 3% alginate (nozzle diameter = 200 μm) and optimization of bio-inks for corneal 3D bioprinting. (a) Digital cornea is imported to the computer driving the 3D printer software slic3r and a preview of the concentric directionality of print is displayed. (b) The support structure is coated with FRESH to facilitate the 3D bioprinting of corneal structures. © View of the 3D bioprinting process. Corneal structures were printed with 3% alginate bio-ink stained with trypan blue to increase visibility. (d) Image of 3D bioprinted corneal structure captured prior to incubation. (e) FRESH is aspirated after 8 min of incubation and corneal structure is carefully removed from support, but begins to unravel 1-day post-printing once keratocytes were combined with the alginate bio-ink. (f) Images of corneal structures 3D bioprinted from composite bio-inks. (g) Relationship between nozzle diameter and printed thickness of corneal structures (left) and depiction of transparency of corneal structure 3D bioprinted from Coll-1 bio-ink. (h) Brightfield image of 3D bioprinted corneal structure containing cells at day 1 (left) and cell viability measurements over 7 days (right). (i) Representative live/dead stain images using fluorescence microscopy at days 1 and 7 after 3D bioprinting in Coll-1. Reproduced from Isaacson et al. (2018), licensed under CC BY 4.0

Bioengineered Cornea Replacements

New Advances In Keratoprostheses Design?

Human Collagen Corneal Implants

Gross appearance of the regenerated cornea of all 10 patients who received bioengineered corneal implants comprising recombinant human collagen. Left two columns: patients at 2 years post-operation. Right two columns: The same patients at 4 years post-surgery. Compiled figures adapted from Fagerholm et al. (2010, 2014), with permission from AAAS and Elsevier.

Bioengineered Corneal Implants As Medicine Delivery Systems?

(Top) From left to right: collagen-based corneal implant; green and blue implants comprising different shaped nanoparticles within a collagen matrix. The differentially shaped nanoparticles confer different absorbance properties, and hence, different colors. (Bottom) Left: Absorption at 600 nm for bacterial suspension of Pseudomonas aeruginosa (strain PAO1) in the presence of hydrogels without and with the different types of AgNPs assessed in this work measured after 24 h. The dashed line in the plot indicates the absorbance of the samples measured at time 0. (Right) Survival colonies cultured after 24 h incubation of incubation of P. aeruginosa cultures in the presence of hydrogels containing the different types of AgNPs employed in this work. Dashed line shows the initial bacteria density. Adapted from Alarcon et al. (2016), with permission from the Royal Society of Chemistry.

Conclusion?

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