Bruch's-Mimetic Nanofibrous Membranes Functionalized with the Integrin-Binding Peptides as a Promising Approach for Human Retinal Pigment Epithelium Cell Transplantation

Shaocheng Wang; Siyong Lin; Bo Xue; Chenyu Wang; Nana Yan; Yueyan Guan; Yuntao Hu; Xuejun Wen

doi:10.3390/molecules27041429

Bruch's-Mimetic Nanofibrous Membranes Functionalized with the Integrin-Binding Peptides as a Promising Approach for Human Retinal Pigment Epithelium Cell Transplantation

Molecules. 2022 Feb 21;27(4):1429. doi: 10.3390/molecules27041429.

Authors

Shaocheng Wang^{1

2

3}, Siyong Lin^{3

4}, Bo Xue³, Chenyu Wang³, Nana Yan^{1

2}, Yueyan Guan^{1

2}, Yuntao Hu⁴, Xuejun Wen^{3

5

6}

Affiliations

¹ Endocrine Department, Third Central Hospital of Tianjin, Tianjin 300170, China.
² Tianjin Key Laboratory of Artificial Cell, Artificial Cell Engineering Technology Research Center of Public Health Ministry, Tianjin 300170, China.
³ Department of Chemical and Life Science Engineering, School of Engineering, Virginia Commonwealth University, Richmond, VA 23284, USA.
⁴ Department of Ophthalmology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, China.
⁵ Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopaedic Department of Tongji Hospital, School of Life Science and Technology, Tongji University, Shanghai 200065, China.
⁶ International Institute for Biomedical Biomaterials (I2BM), Zhengzhou 450018, China.

Abstract

Background: This study aimed to develop an ultrathin nanofibrous membrane able to, firstly, mimic the natural fibrous architecture of human Bruch's membrane (BM) and, secondly, promote survival of retinal pigment epithelial (RPE) cells after surface functionalization of fibrous membranes.

Methods: Integrin-binding peptides (IBPs) that specifically interact with appropriate adhesion receptors on RPEs were immobilized on Bruch's-mimetic membranes to promote coverage of RPEs. Surface morphologies, Fourier-transform infrared spectroscopy spectra, contact angle analysis, Alamar Blue assay, live/dead assay, immunofluorescence staining, and scanning electron microscopy were used to evaluate the outcome.

Results: Results showed that coated membranes maintained the original morphology of nanofibers. After coating with IBPs, the water contact angle of the membrane surfaces varied from 92.38 ± 0.67 degrees to 20.16 ± 0.81 degrees. RPE cells seeded on IBP-coated membranes showed the highest viability at all time points (Day 1, p < 0.05; Day 3, p < 0.01; Days 7 and 14, p < 0.001). The proliferation rate of RPE cells on uncoated poly(ε-caprolactone) (PCL) membranes was significantly lower than that of IBP-coated membranes (p < 0.001). SEM images showed a well-organized hexa/polygonal monolayer of RPE cells on IBP-coated membranes. RPE cells proliferated rapidly, contacted, and became confluent. RPE cells formed a tight adhesion with nanofibers under high-magnification SEM. Our findings confirmed that the IBP-coated PCL membrane improved the attachment, proliferation, and viability of RPE cells. In addition, in this study, we used serum-free culture for RPE cells and short IBPs without immunogenicity to prevent graft rejection and immunogenicity during transplantation.

Conclusions: These results indicated that the biomimic BM-IBP-RPE nanofibrous graft might be a new, practicable approach to increase the success rate of RPE cell transplantation.

Keywords: Bruch’s membrane; cell adhesion; electrospinning; immunogenicity; integrin; nanofibers; peptides; retinal pigment epithelial transplantation.

MeSH terms

Biocompatible Materials
Biomimetics / methods
Bruch Membrane*
Cell Adhesion
Cell Transplantation
Cells, Cultured
Chemical Phenomena
Humans
Integrins / metabolism
Nanofibers* / chemistry
Nanofibers* / ultrastructure
Peptides* / metabolism
Retinal Pigment Epithelium / transplantation*
Spectrum Analysis
Tissue Engineering*

Substances

Biocompatible Materials
Integrins
Peptides