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. 2025 Aug 21;12(8):785.
doi: 10.3390/vetsci12080785.

Biosynthetic Collagen-Analog Hydrogels Stimulate Endogenous Regrowth of Rabbit Corneas: A Pilot Study

Iris Timmerman  1 , Marie-Claude Robert  2 , Claire Vergneau-Grosset  1 , Tristan Juette  1 , Javier Benito  1 , Marta Garbin  1 , Mostafa Zamani-Roudbaraki  2 , Mona Moradi  2 , Hamid Goodarzi  2 , Christos Boutopoulos  2 , Marie-Odile Benoit-Biancamano  1 , May Griffith  2 , Maria Vanore  1
Affiliations

Biosynthetic Collagen-Analog Hydrogels Stimulate Endogenous Regrowth of Rabbit Corneas: A Pilot Study

Iris Timmerman et al. Vet Sci. .

Abstract

Pro-regenerative corneal implants are being developed to improve corneal healing for companion animals in clinical practice. This pilot study evaluated early corneal tissue and nerve regeneration using biosynthetic collagen-analog hydrogels (CAH) in liquid and solid forms. Their efficacy was compared to each other and to allografts on nine white New Zealand rabbits, divided in three groups of three. Each rabbit cornea underwent keratectomy followed by grafting with either a control allograft cornea, liquid injectable, or solid CAH implant. Corneal healing was assessed over 16 weeks using clinical exams, esthesiometry, in vivo confocal microscopy, and optical coherence tomography. One rabbit per group was euthanized at 3, 10, and 16 weeks for histopathological analysis. Both liquid and solid implants enabled corneal re-epithelialization and regeneration of stromal tissue and corneal nerves. Esthesiometric values indicated faster nerve regeneration in rabbits grafted with biosynthetic implants compared to allografts (p < 0.005). By 16 weeks, regenerated neocorneas achieved transparency comparable to allografts. Solid and liquid CAH implants supported complete corneal tissue and nerve regeneration in the studied rabbits. These results suggest that with further research and development, the current gold standard for corneal transplantation could be replaced by high-performing, easily produced biosynthetic alternatives.

Keywords: allografts; anterior lamellar keratoplasty; collagen analogs; corneal regeneration; corneas; rabbits.

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Conflict of interest statement

M.Z.-R., M.-C.R., C.B. and May Griffith (M.G.) are listed as inventors on PCT patent application #CA2024050799—MPC-based copolymers and hydrogels, and uses thereof in regenerative medicine. MC.R is a consultant for Bausch & Lomb, Abbvie, Labtician and EBSCO Health. The other authors declare no conflicts of interest.

Figures

Figure 2
Figure 2
Esthesiometric values of the different groups over time. Data points represent group means, and vertical bars indicate the standard error (SE).
Figure 3
Figure 3
Corneal thickness of the different groups over time. Data points represent group means, and vertical bars indicate the standard error (SE).
Figure 4
Figure 4
Optical coherence tomography (OCT) appearance of rabbit corneas during follow-up. Week 3 follow-up: allograft group (A), solid collagen group (B), liquid collagen group (C), rabbit 7 (D). Week 10 follow-up: allograft group (E), solid collagen group (F), liquid collagen group (G). Week 16 follow-up: allograft group (H), solid collagen group (I), liquid collagen group (J,K). Control group: (L).
Figure 1
Figure 1
Macroscopic appearance of rabbit eyes during follow-up. Week 3 follow-up: allograft group (A), solid collagen group (B), liquid collagen group (C), rabbit 7 (D). Week 10 follow-up: allograft group (E), solid collagen group (F), liquid collagen group (G). Week 16 follow-up: allograft group (H), solid collagen group (I), liquid collagen group (J). Control group: (K).
Figure 5
Figure 5
Confocal microscopy appearance of rabbit corneas during follow-up. Week 10 follow-up: allograft group (A), solid collagen group (B), liquid collagen group (C). Week 16 follow-up: allograft group (D), solid collagen group (E), liquid collagen group (F). Control group: (G).
Figure 6
Figure 6
Histological appearance of rabbit corneas during follow-up at low magnification. Bar = 200 μm. Week 3 follow-up: allograft group (A), solid collagen group (B), liquid collagen group (C). Week 10 follow-up: allograft group (D), solid collagen group (E), liquid collagen group (F). Week 16 follow-up: allograft group (G), solid collagen group (H), liquid collagen group (I). Control group: (J). Black stars indicate liquid CAH remnants and the green arrow indicate fibrin.
Figure 7
Figure 7
Histological appearance of rabbit corneas during follow-up at high magnification. Bar = 50 μm. Week 3 follow-up: allograft group (A), solid collagen group (B), liquid collagen group (C). Week 10 follow-up: allograft group (D), solid collagen group (E), liquid collagen group (F). Week 16 follow-up: allograft group (G), solid collagen group (H), liquid collagen group (I). Control group: (J).
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