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With the goal of entering clinical trials, the present study aimed to (I) transfer the material synthesis of hyaluronic acid\u2013based hydrogels into a routine, pharmaceutical\u2010appropriate production and (II) evaluate the properties of the vitreous substitutes in terms of the current regulations for medical devices (MDR\/ISO standards).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The multistep manufacturing process of the vitreous substitutes, including the modification of hyaluronic acid with glycidyl methacrylate, photocopolymerization with <jats:italic>N<\/jats:italic>\u2010vinylpyrrolidone, and successive hydrogel purification, was developed under laboratory conditions, characterized using <jats:sup>1<\/jats:sup>H\u2010NMR, FT\u2010IR and UV\/Vis spectroscopies and HPLC, and transferred towards a pharmaceutical production environment considering GMP standards. The optical and viscoelastic characteristics of the hyaluronic acid\u2013based hydrogels were compared with those of extracted human vitreous and silicone oil. The effect of the hydrogels on the metabolic activity, proliferation and apoptosis of fibroblast (MRC\u20105, BJ, L929), retinal pigment epithelial (ARPE\u201019, hiPSC\u2010derived RPE) and photoreceptor cells (661W) was studied as well as their mucosal tolerance via a HET\u2010CAM assay.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Hyaluronic acid\u2013based hydrogels having a suitable purity, sterility, high transparency (&gt;90%), appropriate refractive index (1.3365) and viscoelasticity (G\u2032\u2009&gt;\u2009G\u2033) were prepared in a standardized manner under controlled process conditions. The metabolic activity, proliferation and apoptosis of various cell types as well as egg choroid were unaffected by the hyaluronic acid\u2013based vitreous substitutes, demonstrating their biocompatibility.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The present study demonstrates the successful transferability of the crucial synthesis steps of hyaluronic acid\u2013based hydrogels into a routine, GMP\u2010compliant production process while achieving the optical and viscoelastic properties, biocompatibility and purity required for their clinical use as vitreous substitutes.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aos.15301","type":"journal-article","created":{"date-parts":[[2022,12,2]],"date-time":"2022-12-02T10:21:09Z","timestamp":1669976469000},"page":"422-432","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Translation of hyaluronic acid\u2013based vitreous substitutes towards current regulations for medical devices"],"prefix":"10.1111","volume":"101","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2445-9118","authenticated-orcid":false,"given":"Andr\u00e9","family":"Schulz","sequence":"first","affiliation":[{"name":"Eye Clinic Sulzbach, Knappschaft Hospital Saar  Sulzbach Germany"},{"name":"Klaus Heimann Eye Research Institute  Sulzbach Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"Germann","sequence":"additional","affiliation":[{"name":"Fraunhofer Institute for Biomedical Engineering  Sulzbach Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Werner R.","family":"Heinz","sequence":"additional","affiliation":[{"name":"Pharmpur GmbH  K\u00f6nigsbrunn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Engelhard","sequence":"additional","affiliation":[{"name":"Pharmpur GmbH  K\u00f6nigsbrunn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helge","family":"Menz","sequence":"additional","affiliation":[{"name":"Pharmpur GmbH  K\u00f6nigsbrunn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1651-5714","authenticated-orcid":false,"given":"Annekatrin","family":"Rickmann","sequence":"additional","affiliation":[{"name":"Eye Clinic Sulzbach, Knappschaft Hospital Saar  Sulzbach Germany"},{"name":"Klaus Heimann Eye Research Institute  Sulzbach Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ina","family":"Meiser","sequence":"additional","affiliation":[{"name":"Fraunhofer Institute for Biomedical Engineering  Sulzbach Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sascha","family":"Wien","sequence":"additional","affiliation":[{"name":"Fraunhofer Institute for Biomedical Engineering  Sulzbach Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia","family":"Wagner","sequence":"additional","affiliation":[{"name":"Fraunhofer Institute for Biomedical Engineering  Sulzbach Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Januschowski","sequence":"additional","affiliation":[{"name":"Eye Clinic Sulzbach, Knappschaft Hospital Saar  Sulzbach Germany"},{"name":"Klaus Heimann Eye Research Institute  Sulzbach Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Szurman","sequence":"additional","affiliation":[{"name":"Eye Clinic Sulzbach, Knappschaft Hospital Saar  Sulzbach Germany"},{"name":"Klaus Heimann Eye Research Institute  Sulzbach Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,12]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-6420(98)99023-6"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.10605"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.2147\/OPTH.S76947"},{"key":"#cr-split#-e_1_2_6_5_1.1","unstructured":"Chang A.(2019)Vitreous substitutes following vitrectomy surgery.San Francisco CA:Proceedings of the Retina. 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