Development of Biomimetic Substrates for Limbal Epithelial Stem Cells Using Collagen-Based Films, Hyaluronic Acid, Immortalized Cells, and Macromolecular Crowding.

Despite the promising potential of cell-based therapies developed using tissue engineering techniques to treat a wide range of diseases, including limbal stem cell deficiency (LSCD), which leads to corneal blindness, their commercialization remains constrained. This is primarily attributable to the limited cell sources, the use of non-standardizable, unscalable, and unsustainable techniques, and the extended manufacturing processes required to produce transplantable tissue-like surrogates. Herein, we present the first demonstration of the potential of a novel approach combining collagen films (CF), hyaluronic acid (HA), human telomerase-immortalized limbal epithelial stem cells (T-LESCs), and macromolecular crowding (MMC) to develop innovative biomimetic substrates for limbal epithelial stem cells (LESCs).

Macromolecular crowding agent dependent extracellular matrix deposition and growth factor retention in human corneal fibroblast cultures.

The major obstacle in the commercialisation and clinical translation of tissue engineered medicines is the required for the development of implantable tissue surrogates prolonged in vitro culture. Macromolecular crowding (MMC) enhances and accelerates extracellular matrix (ECM) deposition, thus offering an opportunity to bridge the gap between research and development in tissue engineered substitutes. However, the optimal MMC agent is still elusive.

Clinically correlated dose of the amniotic membrane extract is superior to its transplantation in corneal wound healing.

Purpose: This study investigates the superiority of sterile lyophilized amniotic membrane extract (AME) prepared at a clinically correlated dose over amniotic membrane transplantation (AMT) in an experimental corneal wound model.

Methods: AME was prepared from a pool of five amniotic membranes. After homogenizing the membranes, they were lyophilized and sterilized by gamma radiation to obtain sterile, lyophilized AME powder.

Gums as Macromolecular Crowding Agents in Human Skin Fibroblast Cultures.

Even though tissue-engineered medicines are under intense academic, clinical, and commercial investigation, only a handful of products have been commercialised, primarily due to the costs associated with their prolonged manufacturing. While macromolecular crowding has been shown to enhance and accelerate extracellular matrix deposition in eukaryotic cell culture, possibly offering a solution in this procrastinating tissue-engineered medicine development, there is still no widely accepted macromolecular crowding agent. With these in mind, we herein assessed the potential of gum Arabic, gum gellan, gum karaya, and gum xanthan as macromolecular crowding agents in WS1 skin fibroblast cultures (no macromolecular crowding and carrageenan were used as a control).

Corneal fibrosis: From in vitro models to current and upcoming drug and gene medicines.

Fibrotic diseases are characterised by myofibroblast differentiation, uncontrolled pathological extracellular matrix accumulation, tissue contraction, scar formation and, ultimately tissue / organ dysfunction. The cornea, the transparent tissue located on the anterior chamber of the eye, is extremely susceptible to fibrotic diseases, which cause loss of corneal transparency and are often associated with blindness. Although topical corticosteroids and antimetabolites are extensively used in the management of corneal fibrosis, they are associated with glaucoma, cataract formation, corneoscleral melting and infection, imposing the need of far more effective therapies.