Glaucoma is the leading cause of irreversible blindness in the world, currently impacting 80 million people. Patients suffering from primary open-angle glaucoma experience aqueous humor accumulation within the eye causing an increase in intraocular pressure (IOP). The main cause of this rise in IOP is due to poor outflow of aqueous humor through the trabecular meshwork (TM), a tissue composed of collagen and glycosaminoglycans (GAGs) embedded with TM cells. The behavior of TM cells is impacted by their microenvironment, and studies conducted on two-dimensional plastic substrates do not necessarily reflect how TM cells would behave in their native setting. Here, we cultured human TM (hTM) cells on 3D biocompatible hydrogels composed of gelatin methacrylate (GelMA) incorporated with the glycosaminoglycans (GAGs) chondroitin sulfate (CS) and hyaluronic acid (HA). Mechanical properties were quantified by storage moduli and viscosity data. Cellular response was measured by quantifying cellular proliferation and expression of an important extracellular matrix protein, fibronectin. We have shown substrate mechanical properties to impact hTM cell proliferation over 2 weeks. It was found that the incorporation of GAGs impacted cell proliferation and fibronectin expression in hTM cells. This work will help elucidate hTM cell response with changes in their microenvironment.

Hydrogels are three-dimensional networks of hydrophilic polymers that have garnered significant attention as wound-healing materials. Many synthetic hydrogels are fabricated using a radical polymerization approach that requires an initiator molecule that is often photo-or thermosensitive. Initiator-free hydrogels are an emerging area of research that focuses on hydrogel fabrication that occurs in the absence of an initiator or cross-linker molecule, making these hydrogels highly relevant in tissue engineering and regenerative medicine due to their excellent cytocompatibility and ease of scale-up. Here we present on the development of initiator-free zwitterionic hydrogels that photopolymerize without any initiator or cross-linker while under cytocompatible conditions. The hydrogels exhibit a wide range of mechanical characteristics that are dependent on their polymer composition. They resist nonspecific protein adsorption and exhibit a sustained release of proteins and small molecules. Additionally, these self-initiated hydrogels significantly mitigate inflammatory macrophage activation in vitro. Overall, the development of self-initiated photopolymerized zwitterionic hydrogels offers significant progress in the fields of biomaterials and materials science.

Glaucoma is a multifactorial progressive optic neuropathy characterized by the loss of retinal ganglion cells leading to irreversible blindness. It is the leading cause of global irreversible blindness and is currently affecting over 70 million people. Elevated intraocular pressure (IOP) is considered the only modifiable risk factor and is a target of numerous treatment modalities. Researchers have assigned this elevation of IOP to accumulation of extracellular matrix (ECM) components in the aqueous humor (AH) outflow pathway. The major drainage structure for AH outflow is the trabecular meshwork (TM). The ECM of the TM is important in regulating IOP in both normal and glaucomatous eyes. In this work, we have studied the role of exogeneous glycosaminoglycans (GAGs), glucocorticoids, and culture conditions on the expression of the ECM gene and proteins by human TM (hTM) cells cultured on biomaterial scaffolds. Gene and protein expression levels of elastin, laminin, and matrix metalloproteinase-2 (MMP-2) were evaluated using quantitative PCR and immunohistochemistry. Pressure gradient changes in cell-laden scaffolds in perfusion cultures were also monitored. Our findings show that GAGs and dexamethasone play an influencing role in hTM ECM turnover at both transcriptional and translational levels by altering expression levels of elastin, laminin, and MMP-2. Understanding the role of exogeneous factors on hTM cell behavior is helpful in gaining insights on glaucoma pathogenesis and ultimately pivotal in development of novel therapeutics against the disease.

The field of biomaterials aims to improve regenerative outcomes or scientific understanding for a wide range of tissue types and ailments. Biomaterials can be fabricated from natural or synthetic sources and display a plethora of mechanical, electrical, and geometrical properties dependent on their desired application. To date, most biomaterial systems designed for eventual translation to the clinic rely on soluble signaling moieties, such as growth factors, to elicit a specific cellular response. However, these soluble factors are often limited by high cost, convoluted synthesis, low stability, and difficulty in regulation, making the translation of these biomaterials systems to clinical or commercial applications a long and arduous process. In response to this, significant effort has been dedicated to researching cell‐directive biomaterials which can signal for specific cell behavior in the absence of soluble factors. Cells of all tissue types have been shown to be innately in tune with their microenvironment, which is a biological phenomenon that can be exploited by researchers to design materials that direct cell behavior based on their intrinsic characteristics. This review will focus on recent developments in biomaterials that direct cell behavior using biomaterial properties such as charge, peptide presentation, and micro‐ or nano‐geometry. These next generation biomaterials could offer significant strides in the development of clinically relevant medical devices which improve our understanding of the cellular microenvironment and enhance patient care in a variety of ailments.