| 1. |
- Zhang, Wei, et al.
(författare)
-
Sustained Release of TPCA-1 from Silk Fibroin Hydrogels Preserves Keratocyte Phenotype and Promotes Corneal Regeneration by Inhibiting Interleukin-1β Signaling
- 2020
-
Ingår i: Advanced Healthcare Materials. - : Wiley-VCH Verlagsgesellschaft. - 2192-2640 .- 2192-2659. ; 9:17
-
Tidskriftsartikel (refereegranskat)abstract
- Corneal injury due to ocular trauma or infection is one of the most challenging vision impairing pathologies that exists. Many studies focus on the pro-inflammatory and pro-angiogenic effects of interleukin-1 beta(IL-1 beta) on corneal wound healing. However, the effect of IL-1 beta on keratocyte phenotype and corneal repair, as well as the underlying mechanisms, is not clear. This study reports, for the first time, that IL-1 beta induces phenotype changes of keratocytes in vitro, by significantly down-regulating the gene and protein expression levels of keratocyte markers (Keratocan, Lumican, Aldh3a1 and CD34). Furthermore, it is found that the NF-kappa B pathway is involved in the IL-1 beta-induced changes of keratocyte phenotype, and that the selective IKK beta inhibitor TPCA-1, which inhibits NF-kappa B, can preserve keratocyte phenotype under IL-1 beta simulated pathological conditions in vitro. By using a murine model of corneal injury, it is shown that sustained release of TPCA-1 from degradable silk fibroin hydrogels accelerates corneal wound healing, improves corneal transparency, enhances the expression of keratocyte markers, and supports the regeneration of well-organized epithelium and stroma. These findings provide insights not only into the pathophysiological mechanisms of corneal wound healing, but also into the potential development of new treatments for patients with corneal injuries.
|
|
| 2. |
- Zhang, Aini, et al.
(författare)
-
Advances in Regulatory Strategies of Differentiating Stem Cells towards Keratocytes
- 2022
-
Ingår i: Stem Cells International. - : Hindawi Publishing Corporation. - 1687-9678 .- 1687-966X. ; 2022
-
Forskningsöversikt (refereegranskat)abstract
- Corneal injury is a commonly encountered clinical problem which led to vision loss and impairment that affects millions of people worldwide. Currently, the available treatment in clinical practice is corneal transplantation, which is limited by the accessibility of donors. Corneal tissue engineering appears to be a promising alternative for corneal repair. However, current experimental strategies of corneal tissue engineering are insufficient due to inadequate differentiation of stem cell into keratocytes and thus cannot be applied in clinical practice. In this review, we aim to clarify the role and effectiveness of both biochemical factors, physical regulation, and the combination of both to induce stem cells to differentiate into keratocytes. We will also propose novel perspectives of differentiation strategy that may help to improve the efficiency of corneal tissue engineering.
|
|
| 3. |
- Zhang, Wei, et al.
(författare)
-
Tannic acid-mediated dual peptide-functionalized scaffolds to direct stem cell behavior and osteochondral regeneration
- 2020
-
Ingår i: Chemical Engineering Journal. - : Elsevier. - 1385-8947 .- 1873-3212. ; 396
-
Tidskriftsartikel (refereegranskat)abstract
- The development of cell-instructive scaffolds, which provide biochemical cues to direct endogenous bone marrow-derived mesenchymal stem cells (BMSCs) behavior, has the potential to revolutionize osteochondral tissue engineering. However, scaffold material itself is generally lacking the inductive signals. Here, a novel peptide-functionalized scaffold was prepared by prime-coating Ca-alginate scaffold with tannic acid (TA) followed by conjugation of E7/P15 peptides (CA-TA-E7/P15). The system leveraged TA as a reactive intermediate between Ca-alginate and peptides due to the multiple functional groups of TA. These interactions induced by TA prime-coating contributed to enhanced scaffold stability and mechanical properties, increased peptide conjugation and sustained release of peptides without affecting their bioactivity, in a TA concentration-dependent manner. The conjugation of E7/P15 peptides endowed the scaffold with the potential to enhance BMSCs recruitment and deposition of cartilage and bone extracellular matrix (ECM). Furthermore, the prepared CA-TA-E7/P15 scaffold showed a promoted biological performance of simultaneous cartilage and subchondral bone regeneration in rabbit osteochondral defect model. These findings indicate that TA is an effective surface modification intermediate and crosslinking aid, and that the CA-TA-E7/P15 scaffold developed in this study serves as a promising cell-instructive scaffold for osteochondral regeneration.
|
|
