A Mucin-Deficient Ocular Surface Mimetic Platform for Interrogating Drug Effects on Biolubrication, Antiadhesion Properties, and Barrier Functionality.

Dry eye disease (DED) affects more than 100 million people worldwide, causing significant patient discomfort and imposing a multi-billion-dollar burden on global health care systems. In DED patients, the natural biolubrication process that facilitates pain-free blinking goes awry due to an imbalance of lipids, aqueous medium, and mucins in the tear film, resulting in ocular surface damage. Identifying strategies to reduce adhesion and shear stresses between the ocular surface and the conjunctival cells lining the inside of the eyelid during blink cycles is a promising approach to improve the signs and symptoms of DED. However, current preclinical models for screening ocular lubricants rely on scarce, heterogeneous tissue samples or model substrates that do not capture the complex biochemical and biophysical cues present at the ocular surface. To recapitulate the hierarchical architecture and phenotype of the ocular interface for preclinical drug screening, we developed an in vitro mucin-deficient DED model platform that mimics the complexity of the ocular interface and investigated its utility in biolubrication, antiadhesion, and barrier protection studies using recombinant human lubricin, a promising investigational therapy for DED. The biomimetic platform recapitulated the pathological changes in biolubrication, adhesion, and barrier functionality often observed in mucin-deficient DED patients and demonstrated that recombinant human lubricin can reverse the damage induced by mucin loss in a dose- and conformation-dependent manner. Taken together, these results highlight the potential of the platform─and recombinant human lubricin─in advancing the standard of care for mucin-deficient DED patients.

Supramolecular Host-Guest Hydrogels for Corneal Regeneration.

Over 6.2 million people worldwide suffer from moderate to severe vision loss due to corneal disease. While transplantation with allogenic donor tissue is sight-restoring for many patients with corneal blindness, this treatment modality is limited by long waiting lists and high rejection rates, particularly in patients with severe tissue damage and ocular surface pathologies. Hydrogel biomaterials represent a promising alternative to donor tissue for scalable, nonimmunogenic corneal reconstruction. However, implanted hydrogel materials require invasive surgeries and do not precisely conform to tissue defects, increasing the risk of patient discomfort, infection, and visual distortions. Moreover, most hydrogel crosslinking chemistries for the in situ formation of hydrogels exhibit off-target effects such as cross-reactivity with biological structures and/or result in extractable solutes that can have an impact on wound-healing and inflammation. To address the need for cytocompatible, minimally invasive, injectable tissue substitutes, host-guest interactions have emerged as an important crosslinking strategy. This review provides an overview of host-guest hydrogels as injectable therapeutics and highlights the potential application of host-guest interactions in the design of corneal stromal tissue substitutes.

Mucin-Like Glycoproteins Modulate Interfacial Properties of a Mimetic Ocular Epithelial Surface.

Dry eye disease (DED) has high personal and societal costs, but its pathology remains elusive due to intertwined biophysical and biochemical processes at the ocular surface. Specifically, mucin deficiency is reported in a subset of DED patients, but its effects on ocular interfacial properties remain unclear. Herein a novel in vitro mucin-deficient mimetic ocular surface (Mu-DeMOS) with a controllable amount of membrane-tethered mucin molecules is developed to represent the diseased ocular surfaces. Contact angle goniometry on mimetic ocular surfaces reveals that high surface roughness, but not the presence of hydrophilic mucin molecules, delivers constant hydration over native ocular surface epithelia. Live-cell rheometry confirms that the presence of mucin-like glycoproteins on ocular epithelial cells reduces shear adhesive strength at cellular interfaces. Together, optimal surface roughness and surface chemistry facilitate sustainable lubrication for healthy ocular surfaces, while an imbalance between them contributes to lubrication-related dysfunction at diseased ocular epithelial surfaces. Furthermore, the restoration of low adhesive strength at Mu-DeMOS interfaces through a mucin-like glycoprotein, recombinant human lubricin, suggests that increased frictional damage at mucin-deficient cellular surfaces may be reversible. More broadly, these results demonstrate that Mu-DeMOS is a promising platform for drug screening assays and fundamental studies on ocular physiology.

Injectable Cucurbit[8]uril-Based Supramolecular Gelatin Hydrogels for Cell Encapsulation.

Recent efforts to develop hydrogel biomaterials have focused on better recapitulating the dynamic properties of the native extracellular matrix. In hydrogel biomaterials, binding thermodynamics and cross-link kinetics directly affect numerous bulk dynamic properties such as strength, stress relaxation, and material clearance. However, despite the broad range of bulk dynamic properties observed in biological tissues, present strategies to incorporate dynamic linkages in cell-encapsulating hydrogels rely on a relatively small number of dynamic covalent chemical reactions and host-guest interactions. To expand this toolkit, we report the preparation of supramolecular gelatin hydrogels with cucurbit[8]uril (CB[8])-based cross-links that form on demand via thiol-ene reactions between preassembled CB[8]·FGGC peptide ternary complexes and grafted norbornenes. Human fibroblast cells encapsulated within these optically transparent, shear thinning, injectable hydrogels remained highly viable and exhibited a well-spread morphology in culture. These CB[8]-based gelatin hydrogels are anticipated to be useful in applications ranging from bioprinting to cell and drug delivery.