PMID- 33455953 OWN - NLM STAT- MEDLINE DCOM- 20220318 LR - 20220408 IS - 1758-5090 (Electronic) IS - 1758-5082 (Print) IS - 1758-5082 (Linking) VI - 13 IP - 3 DP - 2021 Apr 7 TI - Enhancing islet transplantation using a biocompatible collagen-PDMS bioscaffold enriched with dexamethasone-microplates. LID - 10.1088/1758-5090/abdcac [doi] AB - Islet transplantation is a promising approach to enable type 1 diabetic patients to attain glycemic control independent of insulin injections. However, up to 60% of islets are lost immediately following transplantation. To improve this outcome, islets can be transplanted within bioscaffolds, however, synthetic bioscaffolds induce an intense inflammatory reaction which can have detrimental effects on islet function and survival. In the present study, we first improved the biocompatibility of polydimethylsiloxane (PDMS) bioscaffolds by coating them with collagen. To reduce the inflammatory response to PDMS bioscaffolds, we then enriched the bioscaffolds with dexamethasone-loaded microplates (DEX-muScaffolds). These DEX-microplates have the ability to release DEX in a sustained manner over 7 weeks within a therapeutic range that does not affect the glucose responsiveness of the islets but which minimizes inflammation in the surrounding microenvironment. The bioscaffold showed excellent mechanical properties that enabled it to resist pore collapse thereby helping to facilitate islet seeding and its handling for implantation, and subsequent engraftment, within the epididymal fat pad (EFP). Following the transplantation of islets into the EFP of diabetic mice using DEX-muScaffolds there was a return in basal blood glucose to normal values by day 4, with normoglycemia maintained for 30 d. Furthermore, these animals demonstrated a normal dynamic response to glucose challenges with histological evidence showing reduced pro-inflammatory cytokines and fibrotic tissue surrounding DEX-muScaffolds at the transplantation site. In contrast, diabetic animals transplanted with either islets alone or islets in bioscaffolds without DEX microplates were not able to regain glycemic control during basal conditions with overall poor islet function. Taken together, our data show that coating PDMS bioscaffolds with collagen, and enriching them with DEX-microplates, significantly prolongs and enhances islet function and survival. CI - (c) 2021 IOP Publishing Ltd. FAU - Primavera, Rosita AU - Primavera R AUID- ORCID: 0000-0002-6039-5679 AD - Interventional Regenerative Medicine and Imaging Laboratory, Department of Radiology, Stanford University, Palo Alto, CA 94304, United States of America. AD - Laboratory of Nanotechnology for Precision Medicine, Fondazione Istituto Italiano di Tecnologia, Genoa 16163, Italy. AD - Rosita Primavera and Mehdi Razavi are sharing first authorship of this work. FAU - Razavi, Mehdi AU - Razavi M AD - Interventional Regenerative Medicine and Imaging Laboratory, Department of Radiology, Stanford University, Palo Alto, CA 94304, United States of America. AD - Biionix (Bionic Materials, Implants and Interfaces) Cluster, Department of Internal Medicine, College of Medicine, University of Central Florida, Orlando, FL 32827, United States of America. AD - Rosita Primavera and Mehdi Razavi are sharing first authorship of this work. FAU - Kevadiya, Bhavesh D AU - Kevadiya BD AD - Interventional Regenerative Medicine and Imaging Laboratory, Department of Radiology, Stanford University, Palo Alto, CA 94304, United States of America. FAU - Wang, Jing AU - Wang J AD - Interventional Regenerative Medicine and Imaging Laboratory, Department of Radiology, Stanford University, Palo Alto, CA 94304, United States of America. FAU - Vykunta, Akshara AU - Vykunta A AD - Interventional Regenerative Medicine and Imaging Laboratory, Department of Radiology, Stanford University, Palo Alto, CA 94304, United States of America. FAU - Di Mascolo, Daniele AU - Di Mascolo D AD - Laboratory of Nanotechnology for Precision Medicine, Fondazione Istituto Italiano di Tecnologia, Genoa 16163, Italy. FAU - Decuzzi, Paolo AU - Decuzzi P AUID- ORCID: 0000-0001-6050-4188 AD - Laboratory of Nanotechnology for Precision Medicine, Fondazione Istituto Italiano di Tecnologia, Genoa 16163, Italy. AD - Avnesh S Thakor and Paolo Decuzzi are sharing the senior authorship of this work. FAU - Thakor, Avnesh S AU - Thakor AS AD - Interventional Regenerative Medicine and Imaging Laboratory, Department of Radiology, Stanford University, Palo Alto, CA 94304, United States of America. AD - Avnesh S Thakor and Paolo Decuzzi are sharing the senior authorship of this work. LA - eng GR - P30 DK116074/DK/NIDDK NIH HHS/United States GR - R01 DK119293/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20210407 PL - England TA - Biofabrication JT - Biofabrication JID - 101521964 RN - 0 (Dimethylpolysiloxanes) RN - 0 (Insulin) RN - 7S5I7G3JQL (Dexamethasone) RN - 9007-34-5 (Collagen) SB - IM MH - Animals MH - Collagen/pharmacology MH - Dexamethasone/pharmacology MH - *Diabetes Mellitus, Experimental/therapy MH - Dimethylpolysiloxanes MH - Humans MH - Insulin MH - *Islets of Langerhans MH - *Islets of Langerhans Transplantation MH - Mice PMC - PMC8530023 MID - NIHMS1719497 OTO - NOTNLM OT - bioscaffold OT - dexamethasone OT - diabetes OT - inflammation OT - islet transplantation OT - microplates COIS- Conflict of Interests: The authors declare no conflict of interest. EDAT- 2021/01/19 06:00 MHDA- 2022/03/19 06:00 PMCR- 2022/04/07 CRDT- 2021/01/18 05:27 PHST- 2020/09/30 00:00 [received] PHST- 2021/01/15 00:00 [accepted] PHST- 2021/01/19 06:00 [pubmed] PHST- 2022/03/19 06:00 [medline] PHST- 2021/01/18 05:27 [entrez] PHST- 2022/04/07 00:00 [pmc-release] AID - 10.1088/1758-5090/abdcac [doi] PST - epublish SO - Biofabrication. 2021 Apr 7;13(3):10.1088/1758-5090/abdcac. doi: 10.1088/1758-5090/abdcac.