Tissue engineering for conjunctival reconstruction: Introducing selfassembled collagen-like-peptide scaffolds for the expansion of human conjunctival-derived cells in a xeno-free and serum-free environment. 01/10/2019 - 31/01/2022

Abstract

The human eye is a unique, biological complex but vulnerable entity. It lacks protection of keratinized epithelium against infection and desiccation, as seen in almost every other area of the body. However, the ocular surface is specialised to protect the ocular structures and respond rapidly upon injury, while maintaining a smooth refractive surface to ensure visual acuity. One of the specialised cellular layers contributing to ocular tissue homeostasis is the conjunctiva. This thin mucous membrane belongs to the ocular surface epithelia, covering the sclera and the inside of the eyelids. In some ocular disorders, the conjunctiva is damaged, resulting in extensive scarring and inflammation, which can lead to several pathological conditions such as eyelid distortions, tear film disruptions, severe dry eyes, corneal ulcers and eventually blindness. The management of severe conjunctival surface disorders remains challenging for ophthalmologists worldwide. The conventional treatment comprises the surgical excision of the diseased conjunctiva. Normal wound healing post resection is based on epithelial migration from adjacent healthy conjunctiva to the wounded area. However, this healing process cannot take place in patients lacking sufficient healthy residual conjunctiva. Here, fibrosis and scar formation will occur, often reintroducing several pathological conditions as described above. Hence to avoid sequelae, the ocular surface requires reconstruction post excision using a cellularized conjunctival substitute. In this project, we aim to meet this unmet medical need by creating a cellularized conjunctival substitute for reconstructive surgery. By introducing fully synthetic self-assembling collagen-like-peptide hydrogels as carrier for human conjunctival-derived cells and eliminating all animal-derived components, we aim to provide a safe, consistent and functional conjunctival replacement. The graft's functionality will be tested in vitro by means of specifically designed tests for presence of conjunctival epithelial cells (barrier formation against infectious microbes), mucin-producing goblet cells (tear film stabilization) and stem cells (epithelium renewal).

Researcher(s)

Research team(s)

Project type(s)

  • Research Project

Tissue engineering for conjunctival reconstruction: Introducing self-assembled collagen-like-peptide scaffolds for the expansion of human conjunctival-derived cells in a xeno-free and serum-free environment. 01/10/2017 - 30/09/2019

Abstract

English Title: Tissue engineering for conjunctival reconstruction: Introducing self-assembled collagen-like-peptide scaffolds for the expansion of human conjunctival-derived cells in a xeno-free and serum-free environment. The human eye is a unique, biological complex but vulnerable entity. It lacks protection of keratinized epithelium against infection and desiccation, as seen in almost every other area of the body. However, the ocular surface is specialised to protect the ocular structures and respond rapidly upon injury, while maintaining a smooth refractive surface to ensure visual acuity. One of the specialised cellular layers contributing to ocular tissue homeostasis is the conjunctiva. This thin mucous membrane belongs to the ocular surface epithelia, covering the sclera and the inside of the eyelids. In some ocular disorders, the conjunctiva is damaged, resulting in extensive scarring and inflammation, which can lead to several pathological conditions such as eyelid distortions, tear film disruptions, severe dry eyes, corneal ulcers and eventually blindness. The management of severe conjunctival surface disorders remains challenging for ophthalmologists worldwide. The conventional treatment comprises the surgical excision of the diseased conjunctiva. Normal wound healing post resection is based on epithelial migration from adjacent healthy conjunctiva to the wounded area. However, this healing process cannot take place in patients lacking sufficient healthy residual conjunctiva. Here, fibrosis and scar formation will occur, often reintroducing several pathological conditions as described above. Hence to avoid sequelae, the ocular surface requires reconstruction post excision using a cellularized conjunctival substitute. In this project, we aim to meet this unmet medical need by creating a cellularized conjunctival substitute for reconstructive surgery. By introducing fully synthetic self-assembling collagen-like-peptide hydrogels as carrier for human conjunctival-derived cells and eliminating all animal-derived components, we aim to provide a safe, consistent and functional conjunctival replacement. The graft's functionality will be tested in vitro by means of specifically designed tests for presence of conjunctival epithelial cells (barrier formation against infectious microbes), mucin-producing goblet cells (tear film stabilization) and stem cells (epithelium renewal).

Researcher(s)

Research team(s)

Project type(s)

  • Research Project

Tissue Engineering in Ophthalmology: Regenerating the ocular surface using standardized, xeno-free, tissue-engineered conjunctival grafts for conjunctival reconstruction. 01/10/2016 - 30/09/2017

Abstract

The conjunctiva is a thin membrane, which covers the white part of the eye and the inside of the eyelids. It is essential that this membrane functions correctly as it plays an important role in the maintenance of a healthy ocular surface and the preservation of vision. In some ocular disorders, the conjunctiva is damaged resulting in excessive scarring leading to surface disorders such as severe dry eyes, eyelid distortions and even blindness. Current treatment strategies for conjunctival reconstruction include surgically removing the diseased tissue and placing a human amniotic membrane over the bare sclera to aid in tissue regeneration. However, at times, either due to the nature of the diseased environment or a lack of properly functioning conjunctival epithelial stem cells, there is aberrant wound healing with scar formation, worsening the outlook for ocular reconstruction. In this project, we address this issue by creating a cellularized conjunctival substitute that can be transplanted onto the ocular surface after debridement of diseased tissue. This substitute is expected to reduce/eliminate scar formation and facilitate regeneration by providing a functional conjunctival replacement, containing both mucin-producing goblet cells to stabilize the tear film as well as conjunctival epithelium to establish a barrier to infectious microbes. The human amniotic membrane will be investigated as a biological scaffold for cultivating the cellular grafts for this purpose.

Researcher(s)

Research team(s)

Project type(s)

  • Research Project