Publication:
Optimization of Collagen Chemical Crosslinking to Restore Biocompatibility of Tissue-Engineered Scaffolds

dc.contributor.authorIslam, Mohammad Mirazul
dc.contributor.authorAbuSamra, Dina B.
dc.contributor.authorChivu, Alexandru
dc.contributor.authorArgüeso, Pablo
dc.contributor.authorDohlman, Claes H.
dc.contributor.authorPatra, Hirak K.
dc.contributor.authorChodosh, James
dc.contributor.authorGonzález-Andrades, Miguel
dc.contributor.authoraffiliation[Islam,MM; AbuSamra,DB; Argüeso,P; Dohlman,CH; Chodosh,J; González-Andrades,M] Department of Ophthalmology, Massachusetts Eye and Ear and Schepens Eye Research Institute, Harvard Medical School, Boston, USA. [Chivu,A; Patra,HK] Department of Surgical Biotechnology, University College London, London, UK. [González-Andrades,M] Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Department of Ophthalmology, Reina Sofia University Hospital and University of Cordoba, Cordoba, Spain.
dc.contributor.funderThis research was funded by Boston Keratoprosthesis fund (Boston, MA, USA).
dc.date.accessioned2022-12-05T12:29:05Z
dc.date.available2022-12-05T12:29:05Z
dc.date.issued2021-06-03
dc.description.abstractCollagen scaffolds, one of the most used biomaterials in corneal tissue engineering, are frequently crosslinked to improve mechanical properties, enzyme tolerance, and thermal stability. Crosslinkers such as 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) are compatible with tissues but provide low crosslinking density and reduced mechanical properties. Conversely, crosslinkers such as glutaraldehyde (GTA) can generate mechanically more robust scaffolds; however, they can also induce greater toxicity. Herein, we evaluated the effectivity of double-crosslinking with both EDC and GTA together with the capability of sodium metabisulfite (SM) and sodium borohydride (SB) to neutralize the toxicity and restore biocompatibility after crosslinking. The EDC-crosslinked collagen scaffolds were treated with different concentrations of GTA. To neutralize the free unreacted aldehyde groups, scaffolds were treated with SM or SB. The chemistry involved in these reactions together with the mechanical and functional properties of the collagen scaffolds was evaluated. The viability of the cells grown on the scaffolds was studied using different corneal cell types. The effect of each type of scaffold treatment on human monocyte differentiation was evaluated. One-way ANOVA was used for statistical analysis. The addition of GTA as a double-crosslinking agent significantly improved the mechanical properties and enzymatic stability of the EDC crosslinked collagen scaffold. GTA decreased cell biocompatibility but this effect was reversed by treatment with SB or SM. These agents did not affect the mechanical properties, enzymatic stability, or transparency of the double-crosslinked scaffold. Contact of monocytes with the different scaffolds did not trigger their differentiation into activated macrophages. Our results demonstrate that GTA improves the mechanical properties of EDC crosslinked scaffolds in a dose-dependent manner, and that subsequent treatment with SB or SM partially restores biocompatibility. This novel manufacturing approach would facilitate the translation of collagen-based artificial corneas to the clinical setting.es_ES
dc.description.versionYeses_ES
dc.identifier.citationIslam MM, AbuSamra DB, Chivu A, Argüeso P, Dohlman CH, Patra HK, et al. Optimization of Collagen Chemical Crosslinking to Restore Biocompatibility of Tissue-Engineered Scaffolds. Pharmaceutics. 2021 Jun 3;13(6):832.es_ES
dc.identifier.doi10.3390/pharmaceutics13060832es_ES
dc.identifier.essn1999-4923
dc.identifier.pmcPMC8229326
dc.identifier.pmid34204956es_ES
dc.identifier.urihttp://hdl.handle.net/10668/4457
dc.journal.titlePharmaceutics
dc.language.isoen
dc.page.number16 p.
dc.publisherMDPIes_ES
dc.relation.publisherversionhttps://www.mdpi.com/1999-4923/13/6/832es_ES
dc.rightsAtribución 4.0 Internacional*
dc.rights.accessRightsopen access
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectCorneaes_ES
dc.subjectCollagenes_ES
dc.subjectDouble-crosslinkinges_ES
dc.subjectCarbodiimidees_ES
dc.subjectGlutaraldehydees_ES
dc.subjectSodium metabisulfitees_ES
dc.subjectSodium borohydridees_ES
dc.subjectEDC/NHSes_ES
dc.subjectTissue engineeringes_ES
dc.subjectMacrophageses_ES
dc.subjectCórneaes_ES
dc.subjectColágenoes_ES
dc.subjectCarbodiimidases_ES
dc.subjectGlutarales_ES
dc.subjectBorohidruroses_ES
dc.subjectIngeniería de tejidoses_ES
dc.subjectMateriales biocompatibleses_ES
dc.subject.meshMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humanses_ES
dc.subject.meshMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Culture Techniques::Cell Engineering::Tissue Engineeringes_ES
dc.subject.meshMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Aldehydes::Glutarales_ES
dc.subject.meshMedical Subject Headings::Anatomy::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Monocyteses_ES
dc.subject.meshMedical Subject Headings::Chemicals and Drugs::Macromolecular Substances::Polymers::Biopolymers::Collagenes_ES
dc.subject.meshMedical Subject Headings::Chemicals and Drugs::Biomedical and Dental Materials::Biocompatible Materialses_ES
dc.subject.meshMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Analysis of Variancees_ES
dc.subject.meshMedical Subject Headings::Anatomy::Cells::Connective Tissue Cells::Macrophageses_ES
dc.subject.meshMedical Subject Headings::Anatomy::Sense Organs::Eye::Anterior Eye Segment::Corneaes_ES
dc.titleOptimization of Collagen Chemical Crosslinking to Restore Biocompatibility of Tissue-Engineered Scaffoldses_ES
dc.typeresearch article
dc.type.hasVersionVoR
dspace.entity.typePublication

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