PMID- 34930951 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20240404 IS - 2057-3995 (Electronic) IS - 2057-3995 (Linking) VI - 6 IP - 1 DP - 2021 Dec 20 TI - A bioinspired gelatin-hyaluronic acid-based hybrid interpenetrating network for the enhancement of retinal ganglion cells replacement therapy. PG - 85 LID - 10.1038/s41536-021-00195-3 [doi] LID - 85 AB - Biomaterial-based cell replacement approaches to regenerative medicine are emerging as promising treatments for a wide array of profound clinical problems. Here we report an interpenetrating polymer network (IPN) composed of gelatin-hydroxyphenyl propionic acid and hyaluronic acid tyramine that is able to enhance intravitreal retinal cell therapy. By tuning our bioinspired hydrogel to mimic the vitreous chemical composition and mechanical characteristics we were able to improve in vitro and in vivo viability of human retinal ganglion cells (hRGC) incorporated into the IPN. In vivo vitreal injections of cell-bearing IPN in rats showed extensive attachment to the inner limiting membrane of the retina, improving with hydrogels stiffness. Engrafted hRGC displayed signs of regenerating processes along the optic nerve. Of note was the decrease in the immune cell response to hRGC delivered in the gel. The findings compel further translation of the gelatin-hyaluronic acid IPN for intravitreal cell therapy. CI - (c) 2021. The Author(s). FAU - Dromel, Pierre C AU - Dromel PC AUID- ORCID: 0000-0002-8426-4489 AD - Massachusetts Institute of Technology, Cambridge, MA, USA. AD - Schepens Eye Research Institute of Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, USA. FAU - Singh, Deepti AU - Singh D AD - Schepens Eye Research Institute of Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, USA. FAU - Andres, Eliot AU - Andres E AD - Schepens Eye Research Institute of Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, USA. FAU - Likes, Molly AU - Likes M AD - Wellesley College, Wellesley, MA, USA. FAU - Kurisawa, Motoichi AU - Kurisawa M AD - A*STAR Institute of Bioengineering and Nanotechnology, Singapore, Singapore. FAU - Alexander-Katz, Alfredo AU - Alexander-Katz A AD - Massachusetts Institute of Technology, Cambridge, MA, USA. FAU - Spector, Myron AU - Spector M AD - VA Boston Healthcare System, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. FAU - Young, Michael AU - Young M AUID- ORCID: 0000-0002-6932-5159 AD - Schepens Eye Research Institute of Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, USA. Michael_young@meei.harvard.edu. LA - eng GR - 533330/Rosalinde and Arthur Gilbert Foundation (The Rosalinde and Arthur Gilbert Foundation)/ PT - Journal Article DEP - 20211220 PL - United States TA - NPJ Regen Med JT - NPJ Regenerative medicine JID - 101699846 PMC - PMC8688498 COIS- The authors declare no competing interests. EDAT- 2021/12/22 06:00 MHDA- 2021/12/22 06:01 PMCR- 2021/12/20 CRDT- 2021/12/21 06:18 PHST- 2021/04/16 00:00 [received] PHST- 2021/10/20 00:00 [accepted] PHST- 2021/12/21 06:18 [entrez] PHST- 2021/12/22 06:00 [pubmed] PHST- 2021/12/22 06:01 [medline] PHST- 2021/12/20 00:00 [pmc-release] AID - 10.1038/s41536-021-00195-3 [pii] AID - 195 [pii] AID - 10.1038/s41536-021-00195-3 [doi] PST - epublish SO - NPJ Regen Med. 2021 Dec 20;6(1):85. doi: 10.1038/s41536-021-00195-3.