PMID- 31326656 OWN - NLM STAT- MEDLINE DCOM- 20200921 LR - 20200921 IS - 1878-5905 (Electronic) IS - 0142-9612 (Linking) VI - 218 DP - 2019 Oct TI - An injectable collagen-genipin-carbon dot hydrogel combined with photodynamic therapy to enhance chondrogenesis. PG - 119190 LID - S0142-9612(19)30265-0 [pii] LID - 10.1016/j.biomaterials.2019.05.001 [doi] AB - Collagen has been widely used for cartilage repair, but its low stiffness and rapid degradation disfavor chondrogenesis. Here we conjugated biocompatible carbon dot nanoparticles (CD NPs) onto collagen through a natural product crosslinker (genipin) to prepare an injectable hydrogel (termed collagen-genipin-CD nanoparticles, CGN). The CGN hydrogel showed increased stiffness due to the cross-linking effect of genipin and the presence of CD NPs, and could produce a moderate amount of reactive oxygen species (ROS) by photodynamic therapy (PDT). Both the stiffness enhancement and ROS generation resulted in improved chondrogenic differentiation of bone marrow-derived stem cells (BMSCs) and the subsequent enhanced cartilage regeneration for cartilage defect repair. Specifically, the CGN hydrogel presented a 21-fold higher compression modulus and a 39.3% lower degradation rate than the pure collagen hydrogel. A combination of both PDT and CGN hydrogel increased the BMSCs proliferation by 50.3%, upregulated their expression of cartilage-specific genes by multiple folds, and enhanced GAG secretion by 205.1% on day 21. This combination also accelerated the cartilage regeneration within as short as 8 weeks. The stiffness enhancement and ROS generation synergistically contributed to chondrogenic differentiation by regulating the TGF-beta/SMAD and mTOR signaling pathway, respectively. The combination of CD-modified hydrogel injection and PDT treatment represents a new strategy for minimally invasive repair of cartilage defects. CI - Copyright (c) 2019 Elsevier Ltd. All rights reserved. FAU - Lu, Zhenhui AU - Lu Z AD - Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China; Guangxi Collaborative Innovation Center for Biomedicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China. FAU - Liu, Sijia AU - Liu S AD - Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China; Guangxi Collaborative Innovation Center for Biomedicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China. FAU - Le, Yiguan AU - Le Y AD - Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China; Guangxi Collaborative Innovation Center for Biomedicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China; Department of Orthopaedics Trauma and Hand Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China. FAU - Qin, Zainen AU - Qin Z AD - Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China. FAU - He, Mingwei AU - He M AD - Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China; Guangxi Collaborative Innovation Center for Biomedicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China; Department of Orthopaedics Trauma and Hand Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China. FAU - Xu, Fuben AU - Xu F AD - Guangxi Center for Birth Defects Research and Prevention, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530003, China. FAU - Zhu, Ye AU - Zhu Y AD - Department of Chemistry & Biochemistry, Stephenson Life Sciences Research Center, Institute for Biomedical Engineering, Science and Technology, University of Oklahoma, 101 Stephenson Parkway, Norman, OK 73019-5300, USA. FAU - Zhao, Jinmin AU - Zhao J AD - Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China; Guangxi Collaborative Innovation Center for Biomedicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China; Department of Orthopaedics Trauma and Hand Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China. Electronic address: zhaojinmin@126.com. FAU - Mao, Chuanbin AU - Mao C AD - Department of Chemistry & Biochemistry, Stephenson Life Sciences Research Center, Institute for Biomedical Engineering, Science and Technology, University of Oklahoma, 101 Stephenson Parkway, Norman, OK 73019-5300, USA. Electronic address: cbmao@ou.edu. FAU - Zheng, Li AU - Zheng L AD - Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China; Guangxi Collaborative Innovation Center for Biomedicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China. Electronic address: zhengli224@163.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190712 PL - Netherlands TA - Biomaterials JT - Biomaterials JID - 8100316 RN - 0 (Hydrogels) RN - 0 (Iridoids) RN - 0 (Reactive Oxygen Species) RN - 17778-80-2 (Singlet Oxygen) RN - 7440-44-0 (Carbon) RN - 9007-34-5 (Collagen) RN - A3V2NE52YG (genipin) SB - IM EIN - Biomaterials. 2020 Mar;233:119662. PMID: 31935530 MH - Animals MH - Blotting, Western MH - Carbon/*chemistry MH - Cell Survival/drug effects MH - Chondrogenesis/drug effects MH - Collagen/*chemistry MH - Female MH - Hydrogels/*chemistry/*pharmacology MH - Immunohistochemistry MH - Iridoids/*chemistry MH - Mice MH - Mice, Nude MH - Microscopy, Electron, Transmission MH - Nanocomposites/chemistry/ultrastructure MH - Photochemotherapy/*methods MH - Rats MH - Rats, Sprague-Dawley MH - Reactive Oxygen Species/metabolism MH - Singlet Oxygen/chemistry MH - Spectroscopy, Fourier Transform Infrared OTO - NOTNLM OT - Carbon dots OT - Chondrogenesis OT - Collagen OT - Photodynamic therapy EDAT- 2019/07/22 06:00 MHDA- 2020/09/22 06:00 CRDT- 2019/07/22 06:00 PHST- 2019/04/02 00:00 [received] PHST- 2019/05/02 00:00 [accepted] PHST- 2019/07/22 06:00 [pubmed] PHST- 2020/09/22 06:00 [medline] PHST- 2019/07/22 06:00 [entrez] AID - S0142-9612(19)30265-0 [pii] AID - 10.1016/j.biomaterials.2019.05.001 [doi] PST - ppublish SO - Biomaterials. 2019 Oct;218:119190. doi: 10.1016/j.biomaterials.2019.05.001. Epub 2019 Jul 12.