Eye trabecular meshwork engineered models and perfusion systems for the investigation of glaucoma disease

Abstract

Glaucoma is the second leading cause of irreversible blindness in the world according to the World Health Organization. It is characterized by the progressive degeneration of the optic nerve and despite the significant advances in the field, a cure for glaucoma remains to be found. The trabecular meshwork (TM) has been identified as the key tissue that drives pressure regulation in eye. In this review, we look over the main role of the aforementioned meshwork, as well as its outflow physiology and pathology. Research in the field of glaucoma has mostly progressed by employing animal models. However, these models are often expensive, cumbersome and exhibit a high intra-species variability. The lack of 3D in vitro models complicates the study of TM pressure regulation mechanisms, which makes it difficult to make progress in glaucoma research. In this paper, we review the time evolution of glaucoma models and discuss the ways in which tissue engineering fabrication techniques can be applied to create an artificial TM that serves as a 3D in vitro model. We also study possible outflow evaluation systems that are valid for both scaffold testing and drug screening, which may improve the understanding of TM biology.

Mechanical and morphological modulation of electrospun polymeric scaffolds for tissue engineering applications

“…This study provided an in vitro model to study the AH outflow facility and the role of TM tissue, and presented several advantages over the currently used two-dimensional TM models. With the same aim, another group confirmed PCL scaffolds´s appropriateness for HTMC proliferation and dexamethasone response after a thorough mechanical characterization 163 . In this study, a scaffold holder together with a pressure-controlled system was designed, ultimately showing promising results to carry out drug testing experiments 163 .…”

“…With the same aim, another group confirmed PCL scaffolds´s appropriateness for HTMC proliferation and dexamethasone response after a thorough mechanical characterization 163 . In this study, a scaffold holder together with a pressure-controlled system was designed, ultimately showing promising results to carry out drug testing experiments 163 .…”

“…PCL was selected as our scaffold material because its broad use in SE as TE applications, low degradation rates, biocompatibility, and easy to manipulate 161,163,188 . Previous SEM images and ours shown in Figure 4.1, has revealed the intricate microenvironment of the human TM as a complex meshwork of pores, fibers, and other features of micro-and nano-scale dimensions 200 .…”

“…As we have already mentioned, electrospinning´s primary advantage is its ability to generate highly porous structures and to easily manipulate its fabrication parameters to create scaffolds with different stiffness 187 . We have chosen PCL because its desirable properties (biocompatibility, biodegradability and mechanical characteristics) have already shown promising results mimicking the human TM 161,163,188 . To generate an in vivo like structure and physiology, the fiber diameter, porosity, rigidity, and cell proliferation were evaluated.…”