PMID- 32424991 OWN - NLM STAT- MEDLINE DCOM- 20210514 LR - 20220531 IS - 2192-2659 (Electronic) IS - 2192-2640 (Linking) VI - 9 IP - 13 DP - 2020 Jul TI - Modification of PLGA Scaffold by MSC-Derived Extracellular Matrix Combats Macrophage Inflammation to Initiate Bone Regeneration via TGF-beta-Induced Protein. PG - e2000353 LID - 10.1002/adhm.202000353 [doi] AB - The immunologic response toward chronic inflammation or bone regeneration via the accumulation of M1 or M2 macrophages after injury could determine the fate of biomaterial. Human umbilical cord mesenchymal stem cells (hUCMSCs) have a pivotal immunomodulatory property on directing macrophage behaviors. Herein, for the first time, 3D-printed poly(lactide-co-glycolide) (PLGA) scaffolds modified with hUCMSC-derived extracellular matrix (PLGA-ECM) are prepared by a facile tissue engineering technique with physical decellularization and 2.44 +/- 0.29 mg cm(-3) proteins immobilized on the PLGA-ECM contain multiple soluble cytokines with a sustainable release profile. The PLGA-ECM not only attenuates the foreign body response, but also improves bone regeneration by increasing the accumulation of M2 macrophages in an improved heterotopic transplantation model of SCID mice. Furthermore, the PLGA-ECM scaffolds with the knockdown of transforming growth factor-beta-induced protein (TGFbetaI/betaig-H3) demonstrate that M2 macrophage accumulation improved by the PLGA-ECM could be attributed to increasing the migration of M2 macrophages and the repolarization of M1 macrophages to M2 phenotype, which are mediated by multiple integrin signaling pathways involving in integrin beta7, integrin alpha9, and integrin beta1 in a TGFbetaI-dependent manner. This study presents an effective surface modification strategy of polymeric scaffolds to initiate tissue regeneration and combat inflammatory response by increasing M2 macrophage accumulation. CI - (c) 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. FAU - Deng, Moyuan AU - Deng M AUID- ORCID: 0000-0003-2054-506X AD - National & Regional United Engineering Lab of Tissue Engineering, Department of Orthopaedics, Southwest Hospital, the Third Military Medical University, Chongqing, 400038, China. FAU - Tan, Jiulin AU - Tan J AD - National & Regional United Engineering Lab of Tissue Engineering, Department of Orthopaedics, Southwest Hospital, the Third Military Medical University, Chongqing, 400038, China. FAU - Hu, Chengshen AU - Hu C AD - Research Center for Human Tissue and Organs Degeneration, Institute Biomedical and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China. FAU - Hou, Tianyong AU - Hou T AD - National & Regional United Engineering Lab of Tissue Engineering, Department of Orthopaedics, Southwest Hospital, the Third Military Medical University, Chongqing, 400038, China. FAU - Peng, Wei AU - Peng W AD - National & Regional United Engineering Lab of Tissue Engineering, Department of Orthopaedics, Southwest Hospital, the Third Military Medical University, Chongqing, 400038, China. FAU - Liu, Juan AU - Liu J AD - Research Center for Human Tissue and Organs Degeneration, Institute Biomedical and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China. FAU - Yu, Bo AU - Yu B AD - National & Regional United Engineering Lab of Tissue Engineering, Department of Orthopaedics, Southwest Hospital, the Third Military Medical University, Chongqing, 400038, China. FAU - Dai, Qijie AU - Dai Q AD - National & Regional United Engineering Lab of Tissue Engineering, Department of Orthopaedics, Southwest Hospital, the Third Military Medical University, Chongqing, 400038, China. FAU - Zhou, Jiangling AU - Zhou J AD - National & Regional United Engineering Lab of Tissue Engineering, Department of Orthopaedics, Southwest Hospital, the Third Military Medical University, Chongqing, 400038, China. FAU - Yang, Yusheng AU - Yang Y AD - National & Regional United Engineering Lab of Tissue Engineering, Department of Orthopaedics, Southwest Hospital, the Third Military Medical University, Chongqing, 400038, China. FAU - Dong, Rui AU - Dong R AD - Department of Biomedical Materials Science, College of Biomedical Engineering, Third Military Medical University, Chongqing, 400038, China. FAU - Ruan, Changshun AU - Ruan C AD - Research Center for Human Tissue and Organs Degeneration, Institute Biomedical and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China. FAU - Dong, Shiwu AU - Dong S AD - Department of Biomedical Materials Science, College of Biomedical Engineering, Third Military Medical University, Chongqing, 400038, China. FAU - Xu, Jianzhong AU - Xu J AD - National & Regional United Engineering Lab of Tissue Engineering, Department of Orthopaedics, Southwest Hospital, the Third Military Medical University, Chongqing, 400038, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200519 PL - Germany TA - Adv Healthc Mater JT - Advanced healthcare materials JID - 101581613 RN - 0 (Transforming Growth Factor beta) SB - IM EIN - Adv Healthc Mater. 2021 Jun;10(12):e2100872. PMID: 34159746 MH - Animals MH - Bone Regeneration MH - *Extracellular Matrix MH - Inflammation MH - Macrophages MH - Mice MH - Mice, SCID MH - *Tissue Scaffolds MH - Transforming Growth Factor beta OTO - NOTNLM OT - MSC-derived extracellular matrix OT - TGF-beta-induced protein OT - bone regeneration OT - macrophage inflammation OT - surface modification EDAT- 2020/05/20 06:00 MHDA- 2021/05/15 06:00 CRDT- 2020/05/20 06:00 PHST- 2020/03/03 00:00 [received] PHST- 2020/04/25 00:00 [revised] PHST- 2020/05/20 06:00 [pubmed] PHST- 2021/05/15 06:00 [medline] PHST- 2020/05/20 06:00 [entrez] AID - 10.1002/adhm.202000353 [doi] PST - ppublish SO - Adv Healthc Mater. 2020 Jul;9(13):e2000353. doi: 10.1002/adhm.202000353. Epub 2020 May 19.