Limbal Stem Cells on Bacterial Nanocellulose Carriers for Ocular Surface Regeneration

Abstract

Limbal stem cells (LSCs) are already used in cell‐based treatments for ocular surface disorders. Clinical translation of LSCs‐based therapies critically depends on the successful delivery, survival, and retention of these therapeutic cells to the desired region. Such a major bottleneck could be overcome by using an appropriate carrier to provide anchoring sites and structural support to LSC culture and transplantation. Bacterial nanocellulose (BNC) is an appealing, yet unexplored, candidate for this application because of its biocompatibility, animal‐free origin and mechanical stability. Here, BNC as a vehicle for human embryonic stem cells‐derived LSC (hESC‐LSC) are investigated. To enhance cell‐biomaterial interactions, a plasma activation followed by a Collagen IV and Laminin coating of the BNC substrates is implemented. This surface functionalization with human extracellular matrix proteins greatly improved the attachment and survival of hESC‐LSC without compromising the flexible, robust and semi‐transparent nature of the BNC. The surface characteristics of the BNC substrates are described and a preliminary ex vivo test in simulated transplantation scenarios is provided. Importantly, it is shown that hESC‐LSC retain their self‐renewal and stemness characteristics up to 21 days on BNC substrates. These results open the door for future research on hESC‐LSC/BNC constructs to treat severe ocular surface pathologies.

Highly Aligned Bacterial Nanocellulose Films Obtained During Static Biosynthesis in a Reproducible and Straightforward Approach

“…[ 62 ] Amorphous materials and good thermal insulators tend to be abundant in biologically derived materials; to enhance their thermal conductivity, self‐assembled biomaterials with a higher degree of crystallinity and higher anisotropy are desirable. [ 63 ] BNC has already shown promising results as a scaffold in regenerative medicine, [ 17 , 18 , 19 , 64 ] we studied the influence of the geometrical order on the thermal conductivity of BNC fibers. In particular, we show that it is possible to enhance the thermal conductivity by directional alignment of the fibers, i.e., in the direction parallel to the alignment direction.…”

Bacterial Nanocellulose as a Scaffold for In Vitro Cell Migration Assay

“…Its potential application for invasion testing would require the functionalization of BNC with the extracellular matrix components through chemical or genetic modifications [ 40 , 41 ]. However, the surface functionalization of BNC affects the cells by altering their attachment and survival, which may influence the obtained results when such scaffolds are used for invasion testing [ 18 , 42 , 43 ].…”

Research Progress of Bioinspired Nanostructured Systems for the Treatment of Ocular Disorders

“…However, Anton-Sales et al [ 86 ] found that, compared with the human amniotic membrane, the BNC shows a slightly longer stability and higher mechanical resistance to sutures in vitro under physiological conditions, or ex vivo under simulated physiological conditions. Building on these findings, they attempt to utilize BNC as the carrier for human embryonic stem cell-derived LSC (hESC-LSC) to validate the transplant potential of these cells in a follow-up investigation [ 87 ]. The results showed that self-renewal and stemness characteristics of hESC-LSC can be maintained up to 21 days on the BNC substrates.…”