Retinal-detachment repair and vitreous-like-body reformation via a thermogelling polymer endotamponade

Liu, Zengping; Liow, Sing Shy; Lai, Siew Li; Alli-Shaik, Asfa; Holder, Graham E.; Parikh, Bhav Harshad; Krishnakumar, Subramanian; Liu, Yupeng; Tan, Mein Jin; Gunaratne, Jayantha; Barathi, Veluchamy A; Hunziker, Walter; Lakshminarayanan, Rajamani; Tan, C.H.; Chee, Caroline Ka Lin; Zhao, Peng; Gopal, Lingam; Loh, Xian Jun; Su, Xinyi

doi:10.1038/s41551-019-0382-7

Cited by 87 publications

(126 citation statements)

References 55 publications

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“…2) [45]. Hydrogels have been used as promising materials for a variety of ophthalmic applications [46][47][48][49][50][51][52][53]. However, developing sustained drug delivery systems for biologics such as anti-VEGF molecules is a challenging task.…”

Section: Novel Sustained Drug Delivery Systems For Anti-vegf Agentsmentioning

confidence: 99%

“…Thermo-responsive gels can also be utilized as vitreo-tamponade agents in the treatment of retinal detachment. In a study by Liu et al, a urethane-based thermogelling polymer was able to achieve retinal tamponade in non-human primate vitrectomy models for up to 12 months [47]. Future applications include the incorporation of anti-VEGFs into these gels to serve the dual function of vitreous tamponade and drug delivery.…”

Section: Hydrogels For Sustained Delivery Of Anti-vegfmentioning

confidence: 99%

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Use of biomaterials for sustained delivery of anti-VEGF to treat retinal diseases

Seah

Zhao

Lin

et al. 2020

Eye

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Anti-vascular endothelial growth factors (anti-VEGF) have become the most common treatment modality for many retinal diseases. These include neovascular age-related macular degeneration (n-AMD), proliferative diabetic retinopathy (PDR) and retinal vein occlusions (RVO). However, these drugs are administered via intravitreal injections that are associated with sight-threatening complications. The most feared of these complications is endophthalmitis, a severe infection of the eye with extremely poor visual outcomes. Patients with retinal diseases typically have to undergo multiple injections before achieving the desired therapeutic effect. Each injection incurs the risk of the sight-threatening complications. As such, there has been great interest in developing sustained delivery platforms for anti-VEGF agents to the posterior segment of the eye. In recent years, there have been various strategies that have been conceptualised. These include non-biodegradable implants, nano-formulations and hydrogels. In this review, the barriers of drug delivery to the posterior segment of the eye will be explained. The characteristics of an ideal sustained delivery platform will then be discussed. Finally, the current available strategies will be analysed with the above-mentioned characteristics in mind to determine the advantages and disadvantages of each sustained drug delivery modality. Through the above, this review attempts to provide an overview of the sustained delivery platforms in their various phases of development.These authors contributed equally: Ivan Seah Yu Jun, Zhao Xin Xin 1234567890();,:1234567890();,:

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Section: Novel Sustained Drug Delivery Systems For Anti-vegf Agentsmentioning

confidence: 99%

Section: Hydrogels For Sustained Delivery Of Anti-vegfmentioning

confidence: 99%

Use of biomaterials for sustained delivery of anti-VEGF to treat retinal diseases

Seah

Zhao

Lin

et al. 2020

Eye

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“…It was suggested that the modulus of the in vivo vitreous might be higher compared to the dissected vitreous . However, many of the previously proposed vitreous substitutes have significantly higher modulus values than those of the reported human vitreous humor by orders of magnitude . While the short‐ and immediate‐term in vivo results for some of these hydrogel vitreous substitutes were promising, it remains unclear whether these stiff gels would have long‐term negative effects on the various functions of the eye.…”

Section: Discussionmentioning

confidence: 99%

“…The hydrogel successfully restored the retinal attachment in a rabbit retinal detachment model for up to 410 days without complications. Recently, a tricomponent multi‐block thermogel (termed EPC) was developed as a biodegradable vitreous substitute that can function as a tamponade agent and facilitate the reformation of a vitreous‐like body . The EPC‐7% thermogel showed good functionality for up to 12 months in rabbit and non‐human primate retinal detachment models.…”

Section: Introductionmentioning

confidence: 99%

A Hydrogel Vitreous Substitute that Releases Antioxidant

Tram

Jiang

Torres-Flores

et al. 2019

Macromolecular Bioscience

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Current experimental vitreous substitutes only replace the physical functions of the natural vitreous humor. Removal of the native vitreous disrupts oxygen homeostasis in the eye, causing oxidative damage to the lens that likely results in cataract formation. Neither current clinical treatments nor other experimental vitreous substitutes consider the problem of oxidative stress after vitrectomy. To address this problem, biomimetic hydrogels are prepared by free radical polymerization of poly(ethylene glycol) methacrylate and poly(ethylene glycol) diacrylate. These hydrogels have similar mechanical and optical properties to the vitreous. The hydrogels are injectable through small‐gauge needles and demonstrate in vitro biocompatibility with human retinal and lens epithelial cells. The hydrogels and added vitamin C, an antioxidant, show a synergistic effect in protecting ocular cells against reactive oxygen species, which fulfills a chemical function of the natural vitreous. These hydrogels have the potential to prevent post‐vitrectomy cataract formation and reduce the cost of additional surgeries.

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“…Instead, if the need of a bioinert, stronger and tougher polymer is required, polyurethanes (PUs) are the polymers of choice. PUs are obtained by polycondensation of polyols with n -functional isocyanates [ 115 , 116 , 117 , 118 , 119 , 120 ]. The hydrogels containing biodegradable PUs generally lack elasticity, due to the high crystallinity of the chains.…”

Section: Synthetic Criteria For Hydrogel Productionmentioning

confidence: 99%

Design of Bio-Conjugated Hydrogels for Regenerative Medicine Applications: From Polymer Scaffold to Biomolecule Choice

et al. 2020

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Bio-conjugated hydrogels merge the functionality of a synthetic network with the activity of a biomolecule, becoming thus an interesting class of materials for a variety of biomedical applications. This combination allows the fine tuning of their functionality and activity, whilst retaining biocompatibility, responsivity and displaying tunable chemical and mechanical properties. A complex scenario of molecular factors and conditions have to be taken into account to ensure the correct functionality of the bio-hydrogel as a scaffold or a delivery system, including the polymer backbone and biomolecule choice, polymerization conditions, architecture and biocompatibility. In this review, we present these key factors and conditions that have to match together to ensure the correct functionality of the bio-conjugated hydrogel. We then present recent examples of bio-conjugated hydrogel systems paving the way for regenerative medicine applications.

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Retinal-detachment repair and vitreous-like-body reformation via a thermogelling polymer endotamponade

Cited by 87 publications

References 55 publications

Use of biomaterials for sustained delivery of anti-VEGF to treat retinal diseases

Use of biomaterials for sustained delivery of anti-VEGF to treat retinal diseases

A Hydrogel Vitreous Substitute that Releases Antioxidant

Design of Bio-Conjugated Hydrogels for Regenerative Medicine Applications: From Polymer Scaffold to Biomolecule Choice

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