Rapid bioprinting of conjunctival stem cell micro-constructs for subconjunctival ocular injection.

3D culture Bioprinting Conjunctival stem cell Injectable delivery Ocular surface regeneration Stem cell therapy

Journal

Biomaterials
ISSN: 1878-5905
Titre abrégé: Biomaterials
Pays: Netherlands
ID NLM: 8100316

Informations de publication

Date de publication:
01 2021
Historique:
received: 19 04 2020
revised: 28 09 2020
accepted: 18 10 2020
pubmed: 1 11 2020
medline: 25 5 2021
entrez: 31 10 2020
Statut: ppublish

Résumé

Ocular surface diseases including conjunctival disorders are multifactorial progressive conditions that can severely affect vision and quality of life. In recent years, stem cell therapies based on conjunctival stem cells (CjSCs) have become a potential solution for treating ocular surface diseases. However, neither an efficient culture of CjSCs nor the development of a minimally invasive ocular surface CjSC transplantation therapy has been reported. Here, we developed a robust in vitro expansion method for primary rabbit-derived CjSCs and applied digital light processing (DLP)-based bioprinting to produce CjSC-loaded hydrogel micro-constructs for injectable delivery. Expansion medium containing small molecule cocktail generated fast dividing and highly homogenous CjSCs for more than 10 passages in feeder-free culture. Bioprinted hydrogel micro-constructs with tunable mechanical properties enabled the 3D culture of CjSCs while supporting viability, stem cell phenotype, and differentiation potency into conjunctival goblet cells. These hydrogel micro-constructs were well-suited for scalable dynamic suspension culture of CjSCs and were successfully delivered to the bulbar conjunctival epithelium via minimally invasive subconjunctival injection. This work integrates novel cell culture strategies with bioprinting to develop a clinically relevant injectable-delivery approach for CjSCs towards the stem cell therapies for the treatment of ocular surface diseases.

Identifiants

pubmed: 33129190
pii: S0142-9612(20)30708-0
doi: 10.1016/j.biomaterials.2020.120462
pmc: PMC7719077
mid: NIHMS1644243
pii:
doi:

Substances chimiques

Hydrogels 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

120462

Subventions

Organisme : NCI NIH HHS
ID : P30 CA023100
Pays : United States
Organisme : NIBIB NIH HHS
ID : R01 EB021857
Pays : United States
Organisme : NEI NIH HHS
ID : R21 EY031122
Pays : United States

Informations de copyright

Copyright © 2020 Elsevier Ltd. All rights reserved.

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Auteurs

Zheng Zhong (Z)

Department of NanoEngineering, University of California San Diego, La Jolla, CA, 92093, USA.

Xiaoqian Deng (X)

Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, 90095, USA.

Pengrui Wang (P)

Materials Science and Engineering Program, University of California San Diego, La Jolla, CA, 92093, USA.

Claire Yu (C)

Department of NanoEngineering, University of California San Diego, La Jolla, CA, 92093, USA.

Wisarut Kiratitanaporn (W)

Department of Bioengineering, University of California San Diego, La Jolla, CA, 92093, USA.

Xiaokang Wu (X)

Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.

Jacob Schimelman (J)

Department of NanoEngineering, University of California San Diego, La Jolla, CA, 92093, USA.

Min Tang (M)

Department of NanoEngineering, University of California San Diego, La Jolla, CA, 92093, USA.

Alis Balayan (A)

School of Medicine, University of California San Diego, La Jolla, CA, 92093, USA.

Emmie Yao (E)

Department of NanoEngineering, University of California San Diego, La Jolla, CA, 92093, USA.

Jing Tian (J)

Department of Bioengineering, University of California San Diego, La Jolla, CA, 92093, USA.

Luwen Chen (L)

Department of NanoEngineering, University of California San Diego, La Jolla, CA, 92093, USA.

Kang Zhang (K)

Department of Ophthalmology, University of California San Diego, La Jolla, CA, 92093, USA. Electronic address: kangzhang@gmail.com.

Shaochen Chen (S)

Department of NanoEngineering, University of California San Diego, La Jolla, CA, 92093, USA; Materials Science and Engineering Program, University of California San Diego, La Jolla, CA, 92093, USA; Department of Bioengineering, University of California San Diego, La Jolla, CA, 92093, USA. Electronic address: chen168@eng.ucsd.edu.

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