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Background: The demands on conjunctival replacement tissues are high: they need to be elastic, clinically compatible, surgically feasible and support goblet cell growth., Objective: This article provides an overview of currently applied conjunctival replacement tissues and those under investigation., Method: Current publications on clinically applied conjunctival replacement tissues and substrates which are the subject of scientific research and those already tested in animal models are presented and discussed., Results: Replacement tissues in clinical use are autologous and allogenic conjunctiva, nasal and oral mucous membranes, amniotic membrane and decellularized tissues. Autologous conjunctiva shows good results but is not suitable for large defects due to limited availability. In these cases autologous nasal and oral mucous membranes can be used; however, success is limited in cases of autoimmune diseases. Amniotic membranes are frequently applied clinically but goblet cell growth is limited. Different decellularized tissues are used clinically and goblet cell growth was found in vivo. Robust comparative studies are not yet available. Biological matrices such as fibrin, collagen, elastin, gelatin or hyaluronate and synthetic tissues from the group of polyesters are being investigated in the laboratory and in animal models. These studies show good epithelialization and goblet cell growth in vivo., Conclusion: Transplantation of conjunctiva, nasal and oral mucous membranes and amniotic membranes show satisfactory clinical results but exhibit individual weaknesses. Further studies in animal models and clinical settings are required to further evaluate the benefits of other matrices, such as cell-free tissues or other biological and synthetic matrices., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Purpose: The long-term success of visual rehabilitation in patients with severe conjunctival scarring is reliant on the reconstruction of the conjunctiva with a suitable substitute. The purpose of this study is the development and investigation of a re-epithelialized conjunctival substitute based on porcine decellularized conjunctiva (PDC)., Methods: PDC was re-epithelialized either with pre-expanded human conjunctival epithelial cells (PDC + HCEC) or with a human conjunctival explant placed directly on PDC (PDC + HCEx). Histology and immunohistochemistry were performed to evaluate epithelial thickness, proliferation (Ki67), apoptosis (Caspase 3), goblet cells (MUC5AC), and progenitor cells (CK15, ΔNp63, ABCG2). The superior construct (PDC + HCEx) was transplanted into a conjunctival defect of a rabbit (n = 6). Lissamine green staining verified the epithelialization in vivo. Orbital tissue was exenterated on day 10 and processed for histological and immunohistochemical analysis to examine the engrafted PDC + HCEx. A human-specific antibody was used to detect the transplanted cells., Results: From day-14 in vitro onward, a significantly thicker epithelium and greater number of cells expressing Ki67, CK15, ΔNp63, and ABCG2 were noted for PDC + HCEx versus PDC + HCEC. MUC5AC-positive cells were found only in PDC + HCEx. The PDC + HCEx-grafted rabbit conjunctivas were lissamine-negative during the evaluation period, indicating epithelial integrity. Engrafted PDC + HCEx showed preserved progenitor cell properties and an increased number of goblet cells comparable to those of native conjunctiva., Conclusion: Placing and culturing a human conjunctival explant directly on PDC (PDC + HCEx) enables the generation of a stable, stratified, goblet cell-rich construct that could provide a promising alternative conjunctival substitute for patients with extensive conjunctival stem and goblet cell loss., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Impact Statement: Conjunctival integrity is crucial for a healthy ocular surface and visual acuity. In severe cases of inflammatory surface disorders or after trauma, thermal or chemical burns as well as after ocular surgery, a surgical reconstruction using conjunctival substitutes is required. Due to limitations of currently used substitutes, such as the amniotic membrane, there is a need for the development of new scaffolds of consistent quality for conjunctival reconstruction. This study explored the biocompatibility and surgical usability of plastic-compressed collagen as an alternative conjunctival substitute in a rabbit model.

Conjunctival reconstruction is an integral component of ocular surface restoration. Decellularised tissues are frequently used clinically for tissue engineering. This study identifies porcine decellularised conjunctiva (PDC) and human decellularised conjunctiva (HDC) as promising substitutes for conjunctival reconstruction. PDC and HDC were nearly DNA-free, structurally intact and showed no cytotoxic effects in vitro, which was confirmed by DNA quantification, histology, transmission electron microscopy, collagen quantification and cytotoxicity assay. Comparing the biomechanical properties to amniotic membrane (AM), the most frequently applied matrix for ocular surface reconstruction today, the decellularised conjunctiva was more extensible and elastic but exhibited less tensile strength. The in vivo application in a rabbit model proofed significantly enhanced transplant stability and less suture losses comparing PDC and HDC to AM while none of the matrices induced considerable inflammation. Ten days after implantation, all PDC, 4 of 6 HDC but none of the AM transplants were completely integrated into the recipient conjunctiva with a partially multi-layered epithelium. Altogether, decellularised conjunctivas of porcine and human origin were superior to AM for conjunctival reconstruction after xenogeneic application in vivo., Statement of Significance: Conjunctival integrity is essential for a healthy ocular surface and clear vision. Its reconstruction is required in case of immunological diseases, after trauma, chemical or thermal burns or surgery involving the conjunctiva. Due to limitations of currently used substitute tissues such as amniotic membrane, there is a need for the development of new matrices for conjunctival reconstruction. Decellularised tissues are frequently applied clinically for tissue engineering. The present study identifies porcine and human decellularised conjunctiva as biocompatible and well tolerated scaffolds with superior integration into the recipient conjunctiva compared to amniotic membrane. Decellularised conjunctiva depicts a promising substitute for conjunctival reconstruction in ophthalmology., (Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Reconstruction of the conjunctiva is an essential part of ocular surface reconstruction. Clinically applied and experimentally tested tissue- and stem-cell-based approaches are presented and evaluated., Materials and Methods: Current literature and our own results will be presented., Results: Autologous conjunctiva, mucous membrane of the mouth or nose, and amniotic membrane are routinely used for conjunctival reconstruction. Limitations are limited availability, involvement in autoimmune diseases, donor heterogeneity, and degradation in an inflamed environment. Experimentally tested matrices as tissues made from extracellular matrix proteins, synthetic polymers, temperature-sensitive culture dishes, and decellularized conjunctiva have been tested in vitro and partly in vivo. To replace conjunctival cells, cells of conjunctiva and mucous membrane of mouth and nose have been evaluated and show progenitor cell properties as well as secretory capacity (goblet cell differentiation)., Conclusions: Although different matrices are available for conjunctival reconstruction there is-due to specific limitations of existing tissues-a need for the development of new therapies for conjunctival replacement. Matrices produced in the laboratory have already been partly investigated in vivo and may thus be clinically applicable in the near future. Adult mucous membrane cells show many properties of conjunctival epithelium after expansion in vitro and thus are a promising cell source for conjunctival tissue engineering. Other stem cells sources require further evaluation.

Purpose: When an eye has become irreversibly blind or painful it is removed by enucleation or evisceration. The resulting anophthalmic socket usually receives a volume replacing implant and is subsequently fitted with a prosthetic shell for adequate cosmesis. Trauma, tumour or immunological pathomechanisms can induce loss of bone, orbital soft tissue volume, and conjunctival contraction or implant exposure, which result in difficult or impossible prosthesis wear. In this situation as well as in numerous diseases limited to the conjunctiva (e.g. Pterygium, or cicatrizing conjunctivitis) strategies to substitute the lost tissue are required. Methods: A review of the literature search using various electronic databases (PubMed and MEDLINE) was performed on indications, surgical techniques and materials used to restore the ocular socket. Results: Amniotic membrane and oral mucosa are still the most commonly used substitutes for the reconstruction of larger conjunctival defects and ocular socket reconstruction. However, due to limitations of clinical available grafts, synthetic scaffolds, biomaterials or tissue-engineered grafts have been described in preclinical studies but most of them have not been investigated adequately in clinical studies yet. In orbital volume replacement, porous and nonporous spheres are used and both show acceptable results. However, more clinical studies are required that directly compare the outcomes in patients with similar conditions. Dermofat graft remains a good option in case of sockets with significant orbital volume and conjunctival surface loss. Conclusion: Beyond established techniques using autologous or allogeneic tissue, various approaches of engineering tissue based on scaffolds and stem cell expansion techniques are currently under investigation and may become alternatives in socket reconstruction in the not too far future. [ABSTRACT FROM AUTHOR]

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