{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:57:21Z","timestamp":1785412641413,"version":"3.56.0"},"posted":{"date-parts":[[2025,7,12]]},"group-title":"Bioengineering","reference-count":74,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,7,12]],"date-time":"2025-07-12T00:00:00Z","timestamp":1752278400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["R01 CA256481"],"award-info":[{"award-number":["R01 CA256481"]}],"id":[{"id":"https:\/\/ror.org\/040gcmg81","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01 DK099528"],"award-info":[{"award-number":["R01 DK099528"]}],"id":[{"id":"https:\/\/ror.org\/00adh9b73","id-type":"ROR","asserted-by":"publisher"}]},{"award":["T32 EB019944"],"award-info":[{"award-number":["T32 EB019944"]}],"id":[{"id":"https:\/\/ror.org\/00372qc85","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,7,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>Glioblastoma is the most common primary malignant brain tumor with a five-year survival rate less than 5%. The standard of care involves surgical resection followed by treatment with the alkylating agent temozolomide (TMZ). GBM cells that evade surgery eventually become resistant to TMZ and lead to recurrence of tumors in patients. With only four drugs currently FDA-approved for GBM treatment, there is a need for a clinically relevant model capable of accelerating the identification of new therapies. Microgels are microscale (\u223c10\u20131,000 \u03bcm) hydrogel particles that can be used to encapsulate cells in a tailorable 3D matrix. Microdroplets offer short diffusion lengths relative to conventional hydrogel constructs (&gt;1 mm) to limit spatial distributions of hypoxia and potentially screen therapeutics in a controlled and physiologically relevant environment. Here, we establish a method to encapsulate GBM cells in gelatin and polyethylene glycol (PEG) microgels. We show that microgel composition can affect cell morphology and further, that collections of GBM-laden hydrogels can be used to quantify the effect of single vs. metronomic doses of TMZ. GBM metabolic activity is maintained in microgel culture and GBM cells display drug response kinetics similar to previously established literature using macro-scale hydrogel constructs. Finally, we show microgels can be integrated with a liquid handler to enable high-throughput screening using cell-laden microgels.<\/jats:p>","DOI":"10.1101\/2025.07.08.663758","type":"posted-content","created":{"date-parts":[[2025,7,13]],"date-time":"2025-07-13T05:00:12Z","timestamp":1752382812000},"source":"Crossref","is-referenced-by-count":1,"title":["Hydrogel microdroplet based glioblastoma drug screening platform"],"prefix":"10.64898","author":[{"given":"Brittany A.","family":"Payan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annika Carrillo","family":"Diaz De Leon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tejasvi","family":"Anand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunnar B.","family":"Thompson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Mora-Boza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vishnu V.","family":"Krishnamurthy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9s J.","family":"Garc\u00eda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5458-154X","authenticated-orcid":false,"given":"Brendan A.C.","family":"Harley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025071501201218000_2025.07.08.663758v1.1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noad149"},{"key":"2025071501201218000_2025.07.08.663758v1.2","doi-asserted-by":"crossref","unstructured":"M.E. Davis , Glioblastoma: Overview of Disease and Treatment, Clinical Journal of Oncology Nursing 20 (5) (2016).","DOI":"10.1188\/16.CJON.S1.2-8"},{"key":"2025071501201218000_2025.07.08.663758v1.3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa043330"},{"key":"2025071501201218000_2025.07.08.663758v1.4","doi-asserted-by":"crossref","unstructured":"R. Lakomy , T. Kazda , I. Selingerova , A. Poprach , P. Pospisil , R. Belanova , P. Fadrus , V. Vybihal , M. Smrcka , R. Jancalek , L. Hynkova , K. Muckova , M. Hendrych , J. Sana , O. Slaby , P. Slampa , Real-World Evidence in Glioblastoma: Stupp\u2019s Regimen After a Decade, Frontiers in Oncology 10 (2020).","DOI":"10.3389\/fonc.2020.00840"},{"key":"2025071501201218000_2025.07.08.663758v1.5","doi-asserted-by":"crossref","unstructured":"W. Wu , J.L. Klockow , M. Zhang , F. Lafortune , E. Chang , L. Jin , Y. Wu , H.E. Daldrup-Link , Glioblastoma Multiforme (GBM): An overview of current therapies and mechanisms of resistance, Pharmacological Research 171 (2021).","DOI":"10.1016\/j.phrs.2021.105780"},{"issue":"13","key":"2025071501201218000_2025.07.08.663758v1.6","doi-asserted-by":"crossref","first-page":"3161","DOI":"10.3390\/cancers14133161","article-title":"Survival Outcomes and Prognostic Factors in Glioblastoma","volume":"14","year":"2022","journal-title":"Cancers (Basel"},{"key":"2025071501201218000_2025.07.08.663758v1.7","doi-asserted-by":"crossref","unstructured":"J.P. Fisher , D.C. Adamson , Current FDA-Approved Therapies for High-Grade Malignant Gliomas, Biomedicines 9 (3) (2021).","DOI":"10.3390\/biomedicines9030324"},{"key":"2025071501201218000_2025.07.08.663758v1.8","unstructured":"C. Fernandes , A. Costa , L. Os\u00f3rio , R.C. Lago , P. Linhares , B. Carvalho , C. Caeiro , Chapter 11Current Standards of Care in Glioblastoma Therapy, Codon Publications 2017."},{"issue":"1","key":"2025071501201218000_2025.07.08.663758v1.9","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/s004320050128","article-title":"Preclinical evaluation of 9-chloro-2-methylellipticinium acetate alone and in combination with conventional anticancer drugs for the treatment of human brain tumor xenografts","volume":"124","year":"1998","journal-title":"Journal of Cancer Research and Clinical Oncology"},{"key":"2025071501201218000_2025.07.08.663758v1.10","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.19.9356"},{"key":"2025071501201218000_2025.07.08.663758v1.11","doi-asserted-by":"crossref","unstructured":"J.V.R. Cruz , C. Batista , B.H. Afonso , M.S. Alexandre-Moreira , L.G. Dubois , B. Pontes , V. Moura Neto , F.A. Mendes , Obstacles to Glioblastoma Treatment Two Decades after Temozolomide, Cancers (Basel) 14(13) (2022).","DOI":"10.3390\/cancers14133203"},{"key":"2025071501201218000_2025.07.08.663758v1.12","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-05-2510"},{"issue":"1","key":"2025071501201218000_2025.07.08.663758v1.13","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1002\/gcc.10300","article-title":"Contrasting in vivo and in vitro fates of glioblastoma cell subpopulations with amplified EGFR, Genes","volume":"39","year":"2004","journal-title":"Chromosomes and Cancer"},{"issue":"6","key":"2025071501201218000_2025.07.08.663758v1.14","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1038\/nrclinonc.2012.61","article-title":"Patient-derived tumour xenografts as models for oncology drug development","volume":"9","year":"2012","journal-title":"Nature Reviews Clinical Oncology"},{"key":"2025071501201218000_2025.07.08.663758v1.15","doi-asserted-by":"crossref","unstructured":"K.E.d. Visser , J.A. Joyce , The evolving tumor microenvironment: From cancer initiation to metastatic outgrowth, Cancer Cell 41 (2023).","DOI":"10.1016\/j.ccell.2023.02.016"},{"key":"2025071501201218000_2025.07.08.663758v1.16","unstructured":"N.M. Anderson , M.C. Simon , The tumor microenvironment, Current Biology, Elsevier Inc, 2020, pp. R905\u2013R931."},{"key":"2025071501201218000_2025.07.08.663758v1.17","doi-asserted-by":"crossref","unstructured":"C.J. Jiglairea , N. Baeza-Kalleea , E. Denicola\u00efa , D. Baretsa , P. Metellusa , L. Padovania , O. Chinota , D. Figarella-Brangera , C. Fernandez , Ex vivo cultures of glioblastoma in three-dimensional hydrogel maintain the original tumor growth behavior and are suitable for preclinical drug and radiation sensitivity screening, Experimental Cell Research 321(2) (2014).","DOI":"10.1016\/j.yexcr.2013.12.010"},{"issue":"3","key":"2025071501201218000_2025.07.08.663758v1.18","first-page":"203","article-title":"Engineered Hydrogels for Brain Tumor Culture and Therapy","volume":"3","year":"2021","journal-title":"Bio-Design and Manufacturing"},{"key":"2025071501201218000_2025.07.08.663758v1.19","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-17-2429"},{"key":"2025071501201218000_2025.07.08.663758v1.20","doi-asserted-by":"crossref","unstructured":"S. Pedron , G.L. Wolter , J.-W.E. Chen , S.E. Laken , J.N. Sarkaria , B.A.C. Harley , Hyaluronic acid-functionalized gelatin hydrogels reveal extracellular matrix signals temper the efficacy of erlotinib against patient-derived glioblastoma specimens, Biomaterials 219 (2019).","DOI":"10.1016\/j.biomaterials.2019.119371"},{"issue":"31","key":"2025071501201218000_2025.07.08.663758v1.21","doi-asserted-by":"crossref","first-page":"2201888","DOI":"10.1002\/advs.202201888","article-title":"Perivascular Stromal Cells Instruct Glioblastoma Invasion, Proliferation, and Therapeutic Response within an Engineered Brain Perivascular Niche Model","volume":"9","year":"2022","journal-title":"Advanced Science"},{"key":"2025071501201218000_2025.07.08.663758v1.22","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-19-1305"},{"key":"2025071501201218000_2025.07.08.663758v1.23","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.a.34637"},{"issue":"3","key":"2025071501201218000_2025.07.08.663758v1.24","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1557\/mrc.2017.85","article-title":"Spatially graded hydrogels for preclinical testing of glioblastoma anticancer therapeutics","volume":"7","year":"2017","journal-title":"MRS Communications"},{"key":"2025071501201218000_2025.07.08.663758v1.25","doi-asserted-by":"publisher","DOI":"10.1002\/mabi.201700018"},{"issue":"12","key":"2025071501201218000_2025.07.08.663758v1.26","first-page":"3405","article-title":"The impact of the biophysical features of a 3D gelatin microenvironment on glioblastoma malignancy","volume":"101","year":"2013","journal-title":"J Biomed Mater Res Pt A"},{"key":"2025071501201218000_2025.07.08.663758v1.27","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2013.06.024"},{"issue":"1","key":"2025071501201218000_2025.07.08.663758v1.28","first-page":"20","article-title":"Hydrogel microparticles for biomedical applications","volume":"5","year":"2020","journal-title":"Nat Rev Mater"},{"key":"2025071501201218000_2025.07.08.663758v1.29","doi-asserted-by":"crossref","unstructured":"G.B. Thompson , J. Lee , K.M. Kamani , N. Flores-Velasco , S.A. Rogers , B.A.C. Harley , Granular hydrogels as brittle yield stress fluids, Adv Mater (2025).","DOI":"10.1101\/2025.02.22.639638"},{"key":"2025071501201218000_2025.07.08.663758v1.30","first-page":"100008","article-title":"Granular hydrogels for endogenous tissue repair","volume":"1","year":"2021","journal-title":"Biomater Biosyst"},{"key":"2025071501201218000_2025.07.08.663758v1.31","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbiosy.2021.100008"},{"issue":"1","key":"2025071501201218000_2025.07.08.663758v1.32","first-page":"20","article-title":"Hydrogel microparticles for biomedical applications","volume":"5","year":"2020","journal-title":"Nature Reviews Materials"},{"key":"2025071501201218000_2025.07.08.663758v1.33","doi-asserted-by":"publisher","DOI":"10.1016\/j.copbio.2018.11.001"},{"issue":"20","key":"2025071501201218000_2025.07.08.663758v1.34","doi-asserted-by":"crossref","first-page":"e1705912","DOI":"10.1002\/adma.201705912","article-title":"Injectable Granular Hydrogels with Multifunctional Properties for Biomedical Applications","volume":"30","year":"2018","journal-title":"Adv Mater"},{"key":"2025071501201218000_2025.07.08.663758v1.35","doi-asserted-by":"crossref","unstructured":"D.M. Headen , J.R. Garc\u00eda , A.J. Garc\u00eda , Parallel droplet microfluidics for high throughput cell encapsulation and synthetic microgel generation, Microsystems and Nanoengineering 4 (2018).","DOI":"10.1038\/micronano.2017.76"},{"issue":"19","key":"2025071501201218000_2025.07.08.663758v1.36","doi-asserted-by":"crossref","first-page":"3003","DOI":"10.1002\/adma.201304880","article-title":"Microfluidic-based generation of size-controlled, biofunctionalized synthetic polymer microgels for cell encapsulation","volume":"26","year":"2014","journal-title":"Adv Mater"},{"key":"2025071501201218000_2025.07.08.663758v1.37","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.a.37765"},{"key":"2025071501201218000_2025.07.08.663758v1.38","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.055079"},{"key":"2025071501201218000_2025.07.08.663758v1.39","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.a.37765"},{"key":"2025071501201218000_2025.07.08.663758v1.40","doi-asserted-by":"crossref","unstructured":"G.B. Thompson , J. Lee , K.M. Kamani , N. Flores-Velasco , S.A. Rogers , B.A.C. Harley , Granular hydrogels as brittle yield stress fluids, bioRxiv (2025) 2025.02.22.639638.","DOI":"10.1101\/2025.02.22.639638"},{"key":"2025071501201218000_2025.07.08.663758v1.41","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.actbio.2021.06.028","article-title":"Encapsulation of murine hematopoietic stem and progenitor cells in a thiol-crosslinked maleimide-functionalized gelatin hydrogel","volume":"131","year":"2021","journal-title":"Acta Biomater"},{"key":"2025071501201218000_2025.07.08.663758v1.42","first-page":"20","article-title":"Hydrogel microparticles for biomedical applications","volume":"5","year":"2020","journal-title":"Nature Reviews Materials"},{"key":"2025071501201218000_2025.07.08.663758v1.43","doi-asserted-by":"crossref","unstructured":"A. Sohrabi , A.E.Y.T. Lefebvre , M.J. Harrison , M.C. Condro , T.M. Sanazzaro , G. Safarians , I. Solomon , S. Bastola , S. Kordbacheh , N. Toh , H.I. Kornblum , M.A. Digman , S.K. Seidlits , Microenvironmental stiffness induces metabolic reprogramming in glioblastoma, Cell Reports 42(10) (2023).","DOI":"10.1016\/j.celrep.2023.113175"},{"key":"2025071501201218000_2025.07.08.663758v1.44","doi-asserted-by":"crossref","unstructured":"V. Umesh , A.D. Rape , T.A. Ulrich , S. Kumar , Microenvironmental stiffness enhances glioma cell proliferation by stimulating epidermal growth factor receptor signaling, PLoS One (2014).","DOI":"10.1371\/journal.pone.0101771"},{"key":"2025071501201218000_2025.07.08.663758v1.45","doi-asserted-by":"publisher","DOI":"10.1016\/J.Biomaterials.2011.07.005"},{"key":"2025071501201218000_2025.07.08.663758v1.46","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2010.03.039"},{"issue":"9","key":"2025071501201218000_2025.07.08.663758v1.47","doi-asserted-by":"crossref","first-page":"4531","DOI":"10.1021\/acsabm.2c00598","article-title":"Effect of Chitosan on Alginate-Based Macroporous Hydrogels for the Capture of Glioblastoma Cancer Cells","volume":"5","year":"2022","journal-title":"ACS Applied Bio Materials"},{"key":"2025071501201218000_2025.07.08.663758v1.48","doi-asserted-by":"crossref","unstructured":"S.S. Rao , J. Dejesus , A.R. Short , J.J. Otero , A. Sarkar , J.O. Winter , Glioblastoma behaviors in three-dimensional collagen-hyaluronan composite hydrogels, ACS Applied Materials & Interfaces 5(19) (2013).","DOI":"10.1021\/am402097j"},{"key":"2025071501201218000_2025.07.08.663758v1.49","doi-asserted-by":"crossref","unstructured":"J.E. Chen , S. Pedron , P. Shyu , Y. Hu , J.N. Sarkaria , B.A.C. Harley , Influence of Hyaluronic Acid Transitions in Tumor Microenvironment on Glioblastoma Malignancy and Invasive Behavior, Front Mater 5 (2018).","DOI":"10.3389\/fmats.2018.00039"},{"key":"2025071501201218000_2025.07.08.663758v1.50","doi-asserted-by":"publisher","DOI":"10.1529\/biophysj.105.061994"},{"issue":"1","key":"2025071501201218000_2025.07.08.663758v1.51","doi-asserted-by":"crossref","first-page":"e2202147","DOI":"10.1002\/adhm.202202147","article-title":"Dynamically Crosslinked Poly(ethylene-glycol) Hydrogels Reveal a Critical Role of Viscoelasticity in Modulating Glioblastoma Fates and Drug Responses in 3D","volume":"12","year":"2023","journal-title":"Adv Healthc Mater"},{"issue":"1","key":"2025071501201218000_2025.07.08.663758v1.52","doi-asserted-by":"crossref","first-page":"17727","DOI":"10.1038\/s41598-021-97059-z","article-title":"Gelatin methacrylate hydrogels culture model for glioblastoma cells enriches for mesenchymal-like state and models interactions with immune cells","volume":"11","year":"2021","journal-title":"Scientific Reports"},{"key":"2025071501201218000_2025.07.08.663758v1.53","doi-asserted-by":"crossref","unstructured":"A.R. Short , C. Czeisler , B. Stocker , S. Cole , J.J. Otero , J.O. Winter , Imaging Cell-Matrix Interactions in 3D Collagen Hydrogel Culture Systems, Macromol Biosci 17(6) (2017).","DOI":"10.1002\/mabi.201600478"},{"key":"2025071501201218000_2025.07.08.663758v1.54","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-36347-7"},{"key":"2025071501201218000_2025.07.08.663758v1.55","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.0c01177"},{"key":"2025071501201218000_2025.07.08.663758v1.56","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abe3245"},{"key":"2025071501201218000_2025.07.08.663758v1.57","doi-asserted-by":"publisher","DOI":"10.1038\/nmat4781"},{"key":"2025071501201218000_2025.07.08.663758v1.58","doi-asserted-by":"publisher","DOI":"10.1002\/mabi.201700018"},{"key":"2025071501201218000_2025.07.08.663758v1.59","doi-asserted-by":"publisher","DOI":"10.1007\/s10439-014-1223-1"},{"issue":"1","key":"2025071501201218000_2025.07.08.663758v1.60","doi-asserted-by":"crossref","first-page":"102","DOI":"10.2174\/1874467211205010102","article-title":"Temozolomide: mechanisms of action, repair and resistance","volume":"5","year":"2012","journal-title":"Current molecular pharmacology"},{"key":"2025071501201218000_2025.07.08.663758v1.61","doi-asserted-by":"publisher","DOI":"10.1021\/bi00197a003"},{"issue":"7","key":"2025071501201218000_2025.07.08.663758v1.62","first-page":"2585","article-title":"Temozolomide and Treatment of Malignant Glioma1","volume":"6","year":"2000","journal-title":"Clinical Cancer Research"},{"key":"2025071501201218000_2025.07.08.663758v1.63","doi-asserted-by":"publisher","DOI":"10.1016\/S0305-7372(97)90019-0"},{"key":"2025071501201218000_2025.07.08.663758v1.64","doi-asserted-by":"crossref","unstructured":"V.A. Kriuchkovskaia , E.K. Eames , R.B. Riggins , B.A.C. Harley , Acquired Temozolomide Resistance Instructs Patterns of Glioblastoma Behavior in Gelatin Hydrogels, Advanced healthcare materials (2024) e2400779.","DOI":"10.1101\/2023.11.14.567115"},{"key":"2025071501201218000_2025.07.08.663758v1.65","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-021-08972-5"},{"key":"2025071501201218000_2025.07.08.663758v1.66","doi-asserted-by":"crossref","unstructured":"A.A. Stepanenko , V.P. Chekhonin , On the Critical Issues in Temozolomide Research in Glioblastoma: Clinically Relevant Concentrations and MGMT-independent Resistance, Biomedicines 7(4) (2019).","DOI":"10.3390\/biomedicines7040092"},{"key":"2025071501201218000_2025.07.08.663758v1.67","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-03-0807"},{"key":"2025071501201218000_2025.07.08.663758v1.68","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-09-1349"},{"key":"2025071501201218000_2025.07.08.663758v1.69","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.1992.57"},{"issue":"3","key":"2025071501201218000_2025.07.08.663758v1.70","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.gendis.2016.04.007","article-title":"Temozolomide resistance in glioblastoma multiforme","volume":"3","year":"2016","journal-title":"Genes Dis"},{"issue":"10","key":"2025071501201218000_2025.07.08.663758v1.71","doi-asserted-by":"crossref","first-page":"2400041","DOI":"10.1002\/adtp.202400041","article-title":"Targeting Glioblastoma Tumor Hyaluronan to Enhance Therapeutic Interventions that Regulate Metabolic Cell Properties","volume":"7","year":"2024","journal-title":"Advanced Therapeutics"},{"key":"2025071501201218000_2025.07.08.663758v1.72","doi-asserted-by":"crossref","first-page":"119371","DOI":"10.1016\/j.biomaterials.2019.119371","article-title":"Hyaluronic acid-functionalized gelatin hydrogels reveal extracellular matrix signals temper the efficacy of erlotinib against patient-derived glioblastoma specimens","volume":"219","year":"2019","journal-title":"Biomaterials"},{"key":"2025071501201218000_2025.07.08.663758v1.73","doi-asserted-by":"crossref","unstructured":"A. Brand , L. Allen , M. Altman , M. Hlava , J. Scott , Beyond authorship: attribution, contribution, collaboration, and credit, Learned Publishing 28(2) (2015) 151\u2013155.","DOI":"10.1087\/20150211"},{"key":"2025071501201218000_2025.07.08.663758v1.74","doi-asserted-by":"publisher","DOI":"10.1038\/508312a"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.07.08.663758","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:06:58Z","timestamp":1782277618000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2025.07.08.663758"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,12]]},"references-count":74,"URL":"https:\/\/doi.org\/10.1101\/2025.07.08.663758","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.1002\/jbma.70043","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2025,7,12]]},"subtype":"preprint"}}