{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T03:26:18Z","timestamp":1762917978272,"version":"build-2065373602"},"reference-count":27,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2019,5,30]],"date-time":"2019-05-30T00:00:00Z","timestamp":1559174400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Electric field stimulation is known to affect various cellular processes, including cell fate specification and differentiation, particularly towards neuronal lineages. This makes it a promising therapeutic strategy to stimulate regeneration of neuronal tissues. Retinal ganglion cells (RGCs) is a type of neural cells of the retina responsible for transduction of visual signals from the retina to the brain cortex, and is often degenerated in various blindness-causing retinal diseases. The organic photovoltaic materials such as poly-3-hexylthiophene (P3HT) can generate electric current upon illumination with light of the visible spectrum, and possesses several advantageous properties, including light weight, flexibility and high biocompatibility, which makes them a highly promising tool for electric stimulation of cells in vitro and in vivo. In this study, we tested the ability to generate photocurrent by several formulations of blend (bulk heterojunction) of P3HT (which is electron donor material) with several electron acceptor materials, including Alq3 and bis(10-hydroxybenzo[h]quinolinato)beryllium (Bebq2). We found that the photovoltaic device based on bulk heterojunction of P3HT with Bebq2 could generate photocurrent when illuminated by both green laser and visible spectrum light. We tested the growth and differentiation capacity of human induced pluripotent stem cells (hiPSC)-derived RGCs when grown in interface with such photostimulated device, and found that they were significantly increased. The application of P3HT:Bebq2-formulation of photovoltaic device has a great potential for developments in retinal transplantation, nerve repair and tissue engineering approaches of treatment of retinal degeneration.<\/jats:p>","DOI":"10.3390\/ijms20112661","type":"journal-article","created":{"date-parts":[[2019,5,30]],"date-time":"2019-05-30T11:07:44Z","timestamp":1559214464000},"page":"2661","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["P3HT:Bebq2-Based Photovoltaic Device Enhances Differentiation of hiPSC-Derived Retinal Ganglion Cells"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2354-2999","authenticated-orcid":false,"given":"Chih-Chen","family":"Hsu","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Taipei Veterans General Hospital, Taipei 11217, Taiwan"},{"name":"Institute of Clinical Medicine, National Yang-Ming University, Taipei 11221, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi-Ying","family":"Lin","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology, National Yang-Ming University, Taipei 11221, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3078-8276","authenticated-orcid":false,"given":"Tien-Chun","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Medical Research, Taipei Veterans General Hospital, Taipei 11217, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aliaksandr A.","family":"Yarmishyn","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Taipei Veterans General Hospital, Taipei 11217, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tzu-Wei","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Taipei Veterans General Hospital, Taipei 11217, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuh-Lih","family":"Chang","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology, National Yang-Ming University, Taipei 11221, Taiwan"},{"name":"School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan"},{"name":"Department of Pharmacology, Taipei Veterans General Hospital, Taipei 11217, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6346-8485","authenticated-orcid":false,"given":"De-Kuang","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Taichung Veterans General Hospital, Taichung 40705, Taiwan"},{"name":"Department of Public Health and Institute of Public Health, National Yang-Ming University, Taipei 11217, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chien-Ying","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan"},{"name":"Department of Critical Care Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan"},{"name":"Division of Trauma, Department of Emergency Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yung-Yang","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine, National Yang-Ming University, Taipei 11221, Taiwan"},{"name":"Department of Medical Research, Taipei Veterans General Hospital, Taipei 11217, Taiwan"},{"name":"Department of Chest, Taipei Veterans General Hospital, Taipei 11217, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen-Liang","family":"Lo","sequence":"additional","affiliation":[{"name":"Institute of Oral Biology, National Yang-Ming University, Taipei 11211, Taiwan"},{"name":"Division of Oral and Maxillofacial Surgery, Department of Stomatology, Taipei Veterans General Hospital, Taipei 11217, Taiwan"},{"name":"Department of Dentistry, School of Dentistry, National Yang-Ming University, Taipei 11211, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chi-Hsien","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Shin Kong Wu Ho-Su Memorial Hospital &amp; Fu-Jen Catholic University, Taipei 11101, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shih-Jen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Taipei Veterans General Hospital, Taipei 11217, Taiwan"},{"name":"School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi-Ping","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Medical Research, Taipei Veterans General Hospital, Taipei 11217, Taiwan"},{"name":"School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan"},{"name":"School of Pharmaceutical Sciences, National Yang-Ming University, Taipei 11211, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,5,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4267","DOI":"10.1242\/jcs.023564","article-title":"Electrical dimensions in cell science","volume":"122","author":"McCaig","year":"2009","journal-title":"J. Cell Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3835","DOI":"10.1091\/mbc.e13-12-0708","article-title":"Molecular bioelectricity: How endogenous voltage potentials control cell behavior and instruct pattern regulation in vivo","volume":"25","author":"Levin","year":"2014","journal-title":"Mol. Biol. Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1126\/science.7256258","article-title":"Enhanced spinal cord regeneration in lamprey by applied electric fields","volume":"213","author":"Borgens","year":"1981","journal-title":"Science"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1089\/neu.1999.16.639","article-title":"An imposed oscillating electrical field improves the recovery of function in neurologically complete paraplegic dogs","volume":"16","author":"Borgens","year":"1999","journal-title":"J. Neurotrauma"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3","DOI":"10.3171\/spi.2005.2.1.0003","article-title":"Oscillating field stimulation for complete spinal cord injury in humans: A phase 1 trial","volume":"2","author":"Shapiro","year":"2005","journal-title":"J. Neurosurg. Spine"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1016\/j.wneu.2012.11.039","article-title":"A review of oscillating field stimulation to treat human spinal cord injury","volume":"81","author":"Shapiro","year":"2014","journal-title":"World Neurosurg."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1634\/stemcells.2006-0011","article-title":"Electrical stimulation modulates fate determination of differentiating embryonic stem cells","volume":"25","author":"Yamada","year":"2007","journal-title":"Stem Cells"},{"key":"ref_8","first-page":"5666","article-title":"Biomimetic electrical stimulation platform for neural differentiation of retinal progenitor cells","volume":"2013","author":"Tandon","year":"2013","journal-title":"Conf. Proc. IEEE Eng. Med. Biol. Soc."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"096701","DOI":"10.1088\/0034-4885\/79\/9\/096701","article-title":"Electronic approaches to restoration of sight","volume":"79","author":"Goetz","year":"2016","journal-title":"Rep. Prog. Phys."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1038\/nphoton.2012.104","article-title":"Photovoltaic retinal prosthesis with high pixel density","volume":"6","author":"Mathieson","year":"2012","journal-title":"Nat. Photonics"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1038\/nm.3851","article-title":"Photovoltaic restoration of sight with high visual acuity","volume":"21","author":"Lorach","year":"2015","journal-title":"Nat. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1751","DOI":"10.1002\/adma.201304368","article-title":"A polymer optoelectronic interface provides visual cues to a blind retina","volume":"26","author":"Gautam","year":"2014","journal-title":"Adv. Mater."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"9","DOI":"10.4161\/org.28316","article-title":"Polymer optoelectronic structures for retinal prosthesis","volume":"10","author":"Gautam","year":"2014","journal-title":"Organogenesis"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1038\/ncomms1164","article-title":"A hybrid bioorganic interface for neuronal photoactivation","volume":"2","author":"Ghezzi","year":"2011","journal-title":"Nat. Commun."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1038\/ncomms2057","article-title":"Spin-enhanced organic bulk heterojunction photovoltaic solar cells","volume":"3","author":"Zhang","year":"2012","journal-title":"Nat. Commun."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1038\/nphoton.2013.34","article-title":"A polymer optoelectronic interface restores light sensitivity in blind rat retinas","volume":"7","author":"Ghezzi","year":"2013","journal-title":"Nat. Photonics"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1016\/j.bbagen.2015.01.020","article-title":"Neural stem cell differentiation by electrical stimulation using a cross-linked pedot substrate: Expanding the use of biocompatible conjugated conductive polymers for neural tissue engineering","volume":"1850","author":"Pires","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5885","DOI":"10.1167\/iovs.18-24554","article-title":"In vivo photovoltaic performance of a silicon nanowire photodiode-based retinal prosthesis","volume":"59","author":"Bosse","year":"2018","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1002\/stem.2356","article-title":"Stepwise differentiation of retinal ganglion cells from human pluripotent stem cells enables analysis of glaucomatous neurodegeneration","volume":"34","author":"Ohlemacher","year":"2016","journal-title":"Stem Cells"},{"key":"ref_20","first-page":"1077","article-title":"Three-dimensional retinal organoids from mouse pluripotent stem cells mimic in vivo development with enhanced stratification and rod photoreceptor differentiation","volume":"22","author":"Chen","year":"2016","journal-title":"Mol. Vis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"14520","DOI":"10.1038\/s41598-018-32871-8","article-title":"Three-dimensional retinal organoids facilitate the investigation of retinal ganglion cell development, organization and neurite outgrowth from human pluripotent stem cells","volume":"8","author":"Fligor","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.ydbio.2008.01.015","article-title":"Near complete loss of retinal ganglion cells in the math5\/brn3b double knockout elicits severe reductions of other cell types during retinal development","volume":"316","author":"Moshiri","year":"2008","journal-title":"Dev. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"9275","DOI":"10.1021\/acsami.6b00916","article-title":"Organic photovoltaics and bioelectrodes providing electrical stimulation for pc12 cell differentiation and neurite outgrowth","volume":"8","author":"Hsiao","year":"2016","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4591","DOI":"10.7150\/thno.20169","article-title":"Photoactive poly(3-hexylthiophene) nanoweb for optoelectrical stimulation to enhance neurogenesis of human stem cells","volume":"7","author":"Yang","year":"2017","journal-title":"Theranostics"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e1601699","DOI":"10.1126\/sciadv.1601699","article-title":"Semiconducting polymers are light nanotransducers in eyeless animals","volume":"3","author":"Tortiglione","year":"2017","journal-title":"Sci. Adv."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Bossio, C., Abdel Aziz, I., Tullii, G., Zucchetti, E., Debellis, D., Zangoli, M., Di Maria, F., Lanzani, G., and Antognazza, M.R. (2018). Photocatalytic activity of polymer nanoparticles modulates intracellular calcium dynamics and reactive oxygen species in hek-293 cells. Front. Bioeng. Biotechnol., 6.","DOI":"10.3389\/fbioe.2018.00114"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Lin, T.W., Chien, Y., Lin, Y.Y., Wang, M.L., Yarmishyn, A.A., Yang, Y.P., Hwang, D.K., Peng, C.H., Hsu, C.C., and Chen, S.J. (2019). Establishing liposome-immobilized dexamethasone-releasing pdms membrane for the cultivation of retinal pigment epithelial cells and suppression of neovascularization. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20020241"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/11\/2661\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:54:41Z","timestamp":1760187281000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/11\/2661"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5,30]]},"references-count":27,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2019,6]]}},"alternative-id":["ijms20112661"],"URL":"https:\/\/doi.org\/10.3390\/ijms20112661","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2019,5,30]]}}}