The vitreous humor is a fragile, transparent hydrogel situated between the lens and the retina, occupying 80% of the eye's volume. Due to its viscoelastic behavior, the vitreous serves as a mechanical damper for the eye, absorbing impacts, and protecting the lens and retina. The vitreous liquefies with age, which compromises its function as a shock absorber and causes complications including retinal detachment, macular holes, and vitreous hemorrhage. Studies on the viscoelastic properties of the vitreous have been limited. Rheological testing of the vitreous has commonly been done on non-primate mammalian species. Human vitreous rheological properties have been previously reported; however, various measurement techniques were used, resulting in data that differed by orders of magnitude. Shear rheometry is commonly used to characterize soft tissues and hydrogels such as the vitreous humor. However, no human vitreous rheological data have been reported using this technique, preventing direct comparison to other published work. Additionally, no age-related changes in the mechanical properties of the human vitreous humor have been reported. Human vitreous samples (n = 39, aged 62 ± 15 years) were tested using a shear rheometer. Small amplitude oscillatory shear and creep experiments were performed. The linear viscoelastic region of the human vitreous was found to be below 1% strain. The solid phase of the old human vitreous was found to be stiffer than the young human vitreous and the porcine vitreous. The stiffness of the human vitreous gel also appeared to be positively correlated with age. Vitreous dehydration due to a decrease in hyaluronic acid concentration with age was proposed to cause the stiffening of the solid phase of the vitreous gel. Vitreous liquefaction, therefore, might be characterized as a simultaneous increase in liquid volume and localized stiffening of the vitreous gel. The phase separation of the vitreous humor with age has been hypothesized as the cause of many vitreous-related complications. This study provides viscoelastic properties and age-related changes of the human vitreous humor, which will aid in the design of biomimetic vitreous substitutes, enhancement in analyzing intravitreal transport of therapeutics, and understanding the pathological conditions of the vitreous humor.

The fact that this process of in situ gelation gives rise to hydrogels that are biocompatible and physically and optically similar to the natural vitreous suggests its suitability as a permanent vitreous substitute. Hydrogel candidates will be further studied to evaluate long-term biocompatibility and degradation in vivo.

PurposeAge-related eye diseases are becoming more prevalent. A notable increase has been seen in the most common causes including glaucoma, age-related macular degeneration (AMD), and cataract. Current clinical treatments vary from tissue replacement with polymers to topical eye drops and intravitreal injections. Research and development efforts have increased using polymers for sustained release to the eye to overcome treatment challenges, showing promise in improving drug release and delivery, patient experience, and treatment compliance. Polymers provide unique properties that allow for specific engineered devices to provide improved treatment options. Recent work has shown the utilization of synthetic and biopolymer derived biomaterials in various forms, with this review containing a focus on polymers Food and Drug Administration (FDA) approved for ocular use.MethodsThis provides an overview of some prevalent synthetic polymers and biopolymers used in ocular delivery and their benefits, brief discussion of the various types and synthesis methods used, and administration techniques. Polymers approved by the FDA for different applications in the eye are listed and compared to new polymers being explored in the literature. This article summarizes research findings using polymers for ocular drug delivery from various stages: laboratory, preclinical studies, clinical trials, and currently approved. This review also focuses on some of the challenges to bringing these new innovations to the clinic, including limited selection of approved polymers.ResultsPolymers help improve drug delivery by increasing solubility, controlling pharmacokinetics, and extending release. Several polymer classes including synthetic, biopolymer, and combinations were discussed along with the benefits and challenges of each class. The ways both polymer synthesis and processing techniques can influence drug release in the eye were discussed.ConclusionThe use of biomaterials, specifically polymers, is a well-studied field for drug delivery, and polymers have been used as implants in the eye for over 75 years. Promising new ocular drug delivery systems are emerging using polymers an innovative option for treating ocular diseases because of their tunable properties. This review touches on important considerations and challenges of using polymers for sustained ocular drug delivery with the goal translating research to the clinic.

The primary goal of this research was to characterize the effect of laminin on three-dimensional (3D) neurite growth. Gels were formed using type I collagen at concentrations of 0.4-2.0 mg mL(-1) supplemented with laminin at concentrations of 0, 1, 10, or 100 µg mL(-1). When imaged with confocal microscopy, laminin was shown to follow the collagen fibers; however, the addition of laminin had minimal effect on the stiffness of the scaffolds at any concentration of collagen. Individual neurons dissociated from E9 chick dorsal root ganglia were cultured in the gels for 24 h, and neurite lengths were measured. For collagen gels without laminin, a typical bimodal response of neurite outgrowth was observed, with increased growth at lower concentrations of collagen gel. However, alteration of the chemical nature of the collagen gel by the laminin additive shifted, or completely mitigated, the bimodal neurite growth response seen in gels without laminin. Expression of integrin subunits, α1, α3, α6 and β1, were confirmed by PCR and immunolabeling in the 3D scaffolds. These results provide insight into the interplay between mechanical and chemical environment to support neurite outgrowth in 3D. Understanding the relative impact of environmental factors on 3D nerve growth may improve biomaterial design for nerve cell regeneration.