{"doi":"10.3389/fbioe.2021.686510","title":"Fabrication and Characterization of a Biomaterial Based on Extracellular-Vesicle Functionalized Graphene Oxide","abstract":"Mesenchymal stem cell (MSC) derived extracellular vesicles (EV) are emerging as acellular therapeutics for solid organ injury and as carriers for drug delivery. Graphene-based materials are novel two-dimensional crystal structure-based materials with unique characteristics of stiffness, strength and elasticity that are being explored for various structural and biological applications. We fabricated a biomaterial that would capture desirable properties of both graphene and stem cell derived EV. Metabolically engineered EV that express azide groups were cross-linked with alkyne-functionalized graphene oxide (GO) via a copper catalyzed alkyne-azide cycloaddition (CuAAC) reaction. The crosslinking between EV and GO was accomplished without the need for ligand expression on the metal. Scanning electron and fluorescence microscopy demonstrated excellent cross-linking between EV and GO. Biological effects were assessed by phagocytosis studies and cell viability studies. The uptake of GO or sonicated GO (sGO) resulted in a durable pro-inflammatory immune response. Cell studies further showed that crosslinked GO-EV scaffolds exhibited cell-type dependent cytotoxicity on liver cancer cells whereas there was minimal impact on healthy hepatocyte proliferation. In vitro , neither GO-EV nor sGO-EV induced DNA strand breaks. In vivo studies in zebrafish revealed gross developmental malformations but treatment-induced mortality was only seen with the highest doses of GO-EV and sGO-EV. With these advantages, this engineered biomaterial combining the versatility of graphene with the therapeutic effects of MSC-EV has potential for applications in tissue engineering and regenerative medicine.","journal":"Frontiers in Bioengineering and Biotechnology","year":2021,"id":197912,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9562,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":742708,"name":"Anuradha Moirangthem","orcid":null,"position":1,"is_corresponding":false},{"id":742082,"name":"Irene K. Yan","orcid":"0000-0003-0593-5027","position":2,"is_corresponding":false},{"id":69913,"name":"Tushar Patel","orcid":"0000-0001-7021-9532","position":3,"is_corresponding":false},{"id":742081,"name":"Julia Driscoll","orcid":"0000-0003-4535-8463","position":0,"is_corresponding":true}],"reference_count":35,"raw_metadata":null,"created_at":"2026-07-18T23:50:27.616568Z","pmid":"34178970","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}