{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T13:10:37Z","timestamp":1788354637024,"version":"build-2803163510"},"reference-count":52,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,9,5]],"date-time":"2017-09-05T00:00:00Z","timestamp":1504569600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,9,5]],"date-time":"2017-09-05T00:00:00Z","timestamp":1504569600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Chondral defects pose a great challenge for clinicians to manage owing to the limited capacity for self-healing. Various traditional approaches have been adopted for the repair of these defects with unsatisfactory results. Cartilage tissue engineering techniques have emerged as promising strategies to enhance regeneration and overcome these traditional shortcomings. The cell-homing based technique is considered the most promising owing to its unique advantages. Thermosensitive hydrogels have been applied as scaffolds for biomedical applications with smart sol\u2013gel response for altering environmental temperature. Transforming growth factor (TGF)-\u03b21 is considered to be capable of promoting chondrogenesis. In this study, a novel TGF-\u03b21-loaded poly(\u03b5-caprolactone)\u2013poly(ethylene glycol)\u2013poly(\u03b5-caprolactone) (PCEC) hydrogel was fabricated using simple procedures. Hydrogel characterization, rheological testing, component analysis, and assessment of sol\u2013gel transition, <jats:italic>in vitro<\/jats:italic> degradation, and TGF-\u03b21 release confirmed that this material possesses a porous microstructure with favorable injectability and sustained drug release. Full-thickness cartilage defects were induced on rat knees for <jats:italic>in vivo<\/jats:italic> cartilage repair for eight weeks. Micro-CT and histological evaluation provided further evidence of the optimal capacity of this novel hydrogel for cartilage regeneration with respect to that of other methods. Moreover, our results demonstrated that the cell-free hydrogel is thermosensitive, injectable, biodegradable, and capable of <jats:italic>in vivo<\/jats:italic> cartilage repair and possesses high potential and benefits for acellular cartilage tissue engineering and clinical application in the future.<\/jats:p>","DOI":"10.1038\/s41598-017-11322-w","type":"journal-article","created":{"date-parts":[[2017,8,30]],"date-time":"2017-08-30T14:32:28Z","timestamp":1504103548000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Injectable and thermosensitive TGF-\u03b21-loaded PCEC hydrogel system for in vivo cartilage repair"],"prefix":"10.1038","volume":"7","author":[{"given":"Tengfei","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guo","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taoran","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyu","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sirong","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinfeng","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxiao","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1224-6561","authenticated-orcid":false,"given":"Yunfeng","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,9,5]]},"reference":[{"key":"11322_CR1","doi-asserted-by":"publisher","DOI":"10.1038\/boneres.2016.28","volume":"4","author":"DM Findlay","year":"2016","unstructured":"Findlay, D. M. & Kuliwaba, J. S. Bone-cartilage crosstalk: a conversation for understanding osteoarthritis. Bone Res. \n                           4, 16028 (2016).","journal-title":"Bone Res."},{"key":"11322_CR2","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1177\/0363546515613517","volume":"44","author":"KW Lacy","year":"2016","unstructured":"Lacy, K. W., Cracchiolo, A., Yu, S. & Goitz, H. Medial Femoral Condyle Cartilage Defect Biomechanics: Effect of Obesity, Defect Size, and Cartilage Thickness. Am. J. Sports Med. \n                           44, 409\u2013416 (2016).","journal-title":"Am. J. Sports Med."},{"key":"11322_CR3","doi-asserted-by":"publisher","first-page":"2159","DOI":"10.1002\/jbm.a.35745","volume":"104","author":"N Kitamura","year":"2016","unstructured":"Kitamura, N., Yokota, M., Kurokawa, T., Gong, J. P. & Yasuda, K. In vivo cartilage regeneration induced by a double-network hydrogel: Evaluation of a novel therapeutic strategy for femoral articular cartilage defects in a sheep model. J. Biomed. Mater. Res. A \n                           104, 2159\u20132165 (2016).","journal-title":"J. Biomed. Mater. Res. A"},{"key":"11322_CR4","doi-asserted-by":"publisher","DOI":"10.1186\/s12938-015-0100-y","volume":"14","author":"NJ Chang","year":"2015","unstructured":"Chang, N. J. et al. The repair of full-thickness articular cartilage defect using intra-articular administration of N-acetyl-D-glucosamine in the rabbit knee: randomized controlled trial. Biomed. Eng. Online \n                           14, 105 (2015).","journal-title":"Biomed. Eng. Online"},{"key":"11322_CR5","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/S1359-6101(02)00004-7","volume":"13","author":"E Grimaud","year":"2002","unstructured":"Grimaud, E., Heymann, D. & Redini, F. Recent advances in TGF-beta effects on chondrocyte metabolism. Potential therapeutic roles of TGF-beta in cartilage disorders. Cytokine Growth Factor Rev. \n                           13, 241\u2013257 (2002).","journal-title":"Cytokine Growth Factor Rev."},{"key":"11322_CR6","doi-asserted-by":"publisher","first-page":"2053","DOI":"10.1177\/0363546508328414","volume":"37","author":"K Mithoefer","year":"2009","unstructured":"Mithoefer, K., McAdams, T., Williams, R. J., Kreuz, P. C. & Mandelbaum, B. R. Clinical efficacy of the microfracture technique for articular cartilage repair in the knee: an evidence-based systematic analysis. Am. J. Sports Med. \n                           37, 2053\u20132063 (2009).","journal-title":"Am. J. Sports Med."},{"key":"11322_CR7","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1016\/j.arthro.2010.08.007","volume":"27","author":"JD Harris","year":"2011","unstructured":"Harris, J. D., Cavo, M., Brophy, R., Siston, R. & Flanigan, D. Biological knee reconstruction: a systematic review of combined meniscal allograft transplantation and cartilage repair or restoration. Arthroscopy \n                           27, 409\u2013418 (2011).","journal-title":"Arthroscopy"},{"key":"11322_CR8","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1016\/j.knee.2007.06.008","volume":"14","author":"D Matsunaga","year":"2007","unstructured":"Matsunaga, D., Akizuki, S., Takizawa, T., Yamazaki, I. & Kuraishi, J. Repair of articular cartilage and clinical outcome after osteotomy with microfracture or abrasion arthroplasty for medial gonarthrosis. Knee \n                           14, 465\u2013471 (2007).","journal-title":"Knee"},{"key":"11322_CR9","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1159\/000147313","volume":"144","author":"J Bruns","year":"1992","unstructured":"Bruns, J., Meyer-Pannwitt, U. & Silbermann, M. The rib perichondrium. An anatomical study in sheep of a tissue used as transplant in the treatment of hyaline-cartilage defects. Acta Anat (Basel). \n                           144, 258\u2013266 (1992).","journal-title":"Acta Anat (Basel)."},{"key":"11322_CR10","first-page":"13","volume":"18","author":"C Perka","year":"2000","unstructured":"Perka, C. et al. Joint cartilage repair with transplantation of embryonic chondrocytes embedded in collagen-fibrin matrices. Clin Exp Rheumatol \n                           18, 13\u201322 (2000).","journal-title":"Clin Exp Rheumatol"},{"key":"11322_CR11","first-page":"683","volume":"23","author":"FY Yu","year":"2010","unstructured":"Yu, F. Y. et al. Mechanisms of autologous chondrocytes mass transplantation in the repair of cartilage defects of rabbits\u2019 knee. Zhongguo Gu Shang \n                           23, 683\u2013687 (2010).","journal-title":"Zhongguo Gu Shang"},{"key":"11322_CR12","doi-asserted-by":"publisher","first-page":"185","DOI":"10.2106\/00004623-200302000-00001","volume":"85-A","author":"U Horas","year":"2003","unstructured":"Horas, U., Pelinkovic, D., Herr, G., Aigner, T. & Schnettler, R. Autologous chondrocyte implantation and osteochondral cylinder transplantation in cartilage repair of the knee joint. A prospective, comparative trial. J. Bone Joint Surg. Am. \n                           85-A, 185\u2013192 (2003).","journal-title":"A prospective, comparative trial. J. Bone Joint Surg. Am."},{"key":"11322_CR13","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0088550","volume":"9","author":"L Lin","year":"2014","unstructured":"Lin, L. et al. Sonic hedgehog improves redifferentiation of dedifferentiated chondrocytes for articular cartilage repair. PLoS One \n                           9, e88550 (2014).","journal-title":"PLoS One"},{"key":"11322_CR14","doi-asserted-by":"publisher","DOI":"10.1002\/smll.201602770","volume":"13","author":"X Shao","year":"2017","unstructured":"Shao, X. et al. Tetrahedral DNA Nanostructure: A Potential Promoter for Cartilage Tissue Regeneration via Regulating Chondrocyte Phenotype and Proliferation. Small \n                           13, 201602770, doi:10.1002\/smll.201602770 (2017).","journal-title":"Small"},{"key":"11322_CR15","doi-asserted-by":"publisher","DOI":"10.1038\/boneres.2017.18","volume":"5","author":"J Liao","year":"2017","unstructured":"Liao, J. et al. The fabrication of biomimetic biphasic CAN-PAC hydrogel with a seamless interfacial layer applied in osteochondral defect repair. Bone Res. \n                           5, 17018 (2017).","journal-title":"Bone Res."},{"key":"11322_CR16","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1111\/cpr.12152","volume":"48","author":"C Zhou","year":"2015","unstructured":"Zhou, C. et al. Tetraploid complementation proves pluripotency of induced pluripotent stem cells derived from adipose tissue. Cell Prolif. \n                           48, 39\u201346 (2015).","journal-title":"Cell Prolif."},{"key":"11322_CR17","doi-asserted-by":"publisher","first-page":"248","DOI":"10.22203\/eCM.v025a18","volume":"25","author":"B Johnstone","year":"2013","unstructured":"Johnstone, B. et al. Tissue engineering for articular cartilage repair\u2013the state of the art. Eur. Cell Mater. \n                           25, 248\u2013267 (2013).","journal-title":"Eur. Cell Mater."},{"key":"11322_CR18","doi-asserted-by":"publisher","first-page":"9608","DOI":"10.1016\/j.biomaterials.2014.08.020","volume":"35","author":"H Huang","year":"2014","unstructured":"Huang, H. et al. A functional biphasic biomaterial homing mesenchymal stem cells for in vivo cartilage regeneration. Biomaterials \n                           35, 9608\u20139619 (2014).","journal-title":"Biomaterials"},{"key":"11322_CR19","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1016\/S0140-6736(10)60668-X","volume":"376","author":"CH Lee","year":"2010","unstructured":"Lee, C. H. et al. Regeneration of the articular surface of the rabbit synovial joint by cell homing: a proof of concept study. Lancet \n                           376, 440\u2013448 (2010).","journal-title":"Lancet"},{"key":"11322_CR20","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1016\/j.biomaterials.2014.10.049","volume":"39","author":"P Chen","year":"2015","unstructured":"Chen, P. et al. Radially oriented collagen scaffold with SDF-1 promotes osteochondral repair by facilitating cell homing. Biomaterials \n                           39, 114\u2013123 (2015).","journal-title":"Biomaterials"},{"key":"11322_CR21","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1016\/j.ejpb.2004.03.019","volume":"58","author":"E Ruel-Gariepy","year":"2004","unstructured":"Ruel-Gariepy, E. & Leroux, J. C. In situ-forming hydrogels\u2013review of temperature-sensitive systems. Eur. J. Pharm. Biopharm. \n                           58, 409\u2013426 (2004).","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"11322_CR22","doi-asserted-by":"publisher","first-page":"6020","DOI":"10.1016\/j.biomaterials.2012.04.050","volume":"33","author":"T Billiet","year":"2012","unstructured":"Billiet, T., Vandenhaute, M., Schelfhout, J., Van, V. S. & Dubruel, P. A review of trends and limitations in hydrogel-rapid prototyping for tissue engineering. Biomaterials \n                           33, 6020\u20136041 (2012).","journal-title":"Biomaterials"},{"key":"11322_CR23","doi-asserted-by":"publisher","first-page":"561","DOI":"10.3390\/s8010561","volume":"8","author":"A Richter","year":"2008","unstructured":"Richter, A. et al. Review on Hydrogel-based pH Sensors and Microsensors. Sensors (Basel) \n                           8, 561\u2013581 (2008).","journal-title":"Sensors (Basel)"},{"key":"11322_CR24","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/j.jare.2013.07.006","volume":"6","author":"EM Ahmed","year":"2015","unstructured":"Ahmed, E. M. Hydrogel: Preparation, characterization, and applications: A review. J. Adv. Res. \n                           6, 105\u2013121 (2015).","journal-title":"J. Adv. Res."},{"key":"11322_CR25","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1002\/jbm.b.30858","volume":"84","author":"CB Liu","year":"2008","unstructured":"Liu, C. B. et al. Thermoreversible gel-sol behavior of biodegradable PCL-PEG-PCL triblock copolymer in aqueous solutions. J. Biomed. Mater. Res. B Appl. Biomater \n                           84, 165\u2013175 (2008).","journal-title":"J. Biomed. Mater. Res. B Appl. Biomater"},{"key":"11322_CR26","doi-asserted-by":"publisher","first-page":"1276","DOI":"10.1002\/jbm.a.35253","volume":"103","author":"M Boffito","year":"2015","unstructured":"Boffito, M., Sirianni, P., Di, R. A. & Chiono, V. Thermosensitive block copolymer hydrogels based on poly(varepsilon-caprolactone) and polyethylene glycol for biomedical applications: state of the art and future perspectives. J. Biomed. Mater. Res. A \n                           103, 1276\u20131290 (2015).","journal-title":"J. Biomed. Mater. Res. A"},{"key":"11322_CR27","doi-asserted-by":"publisher","first-page":"1985","DOI":"10.1002\/app.31893","volume":"116","author":"G Ma","year":"2010","unstructured":"Ma, G., Miao, B. & Song, C. Thermosensitive PCL-PEG-PCL hydrogels: Synthesis, characterization, and delivery of proteins. J. Appl. Polym. Sci. \n                           116, 1985\u20131993 (2010).","journal-title":"J. Appl. Polym. Sci."},{"key":"11322_CR28","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1108\/13552541111138414","volume":"17","author":"CP Jiang","year":"2011","unstructured":"Jiang, C. P., Huang, J. R. & Hsieh, M. F. Fabrication of synthesized PCL\u2010PEG\u2010PCL tissue engineering scaffolds using an air pressure\u2010aided deposition system. Rapid Prototyp. J. \n                           17, 288\u2013297 (2011).","journal-title":"Rapid Prototyp. J."},{"key":"11322_CR29","doi-asserted-by":"publisher","first-page":"18372","DOI":"10.1021\/jp106488t","volume":"114","author":"S Fu","year":"2010","unstructured":"Fu, S. et al. Preparation and Characterization of Nano-Hydroxyapatite\/Poly(\u03b5-caprolactone)\u2212Poly(ethylene glycol)\u2212Poly(\u03b5-caprolactone) Composite Fibers for Tissue Engineering. J. Phys. Chem. C \n                           114, 18372\u201318378 (2010).","journal-title":"J. Phys. Chem. C"},{"key":"11322_CR30","doi-asserted-by":"publisher","first-page":"E485","DOI":"10.1002\/term.1846","volume":"10","author":"CY Ko","year":"2016","unstructured":"Ko, C. Y. et al. In vitro and in vivo co-culture of chondrocytes and bone marrow stem cells in photocrosslinked PCL-PEG-PCL hydrogels enhances cartilage formation. J. Tissue Eng. Regen. Med. \n                           10, E485\u2013E496 (2016).","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"11322_CR31","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1111\/cpr.12295","volume":"49","author":"N Fu","year":"2016","unstructured":"Fu, N. et al. PCL-PEG-PCL film promotes cartilage regeneration in vivo. Cell Prolif. \n                           49, 729\u2013739 (2016).","journal-title":"Cell Prolif."},{"key":"11322_CR32","doi-asserted-by":"publisher","first-page":"1148","DOI":"10.1177\/0885328216680152","volume":"31","author":"E Pazarceviren","year":"2017","unstructured":"Pazarceviren, E., Erdemli, O., Keskin, D. & Tezcaner, A. Clinoptilolite\/PCL-PEG-PCL composite scaffolds for bone tissue engineering applications. J. Biomater. Appl. \n                           31, 1148\u20131168 (2017).","journal-title":"J. Biomater. Appl."},{"key":"11322_CR33","doi-asserted-by":"publisher","first-page":"3545","DOI":"10.2147\/IJN.S97063","volume":"11","author":"J Hou","year":"2016","unstructured":"Hou, J. et al. Degradability, cytocompatibility, and osteogenesis of porous scaffolds of nanobredigite and PCL-PEG-PCL composite. Int. J. Nanomedicine \n                           11, 3545\u20133555 (2016).","journal-title":"Int. J. Nanomedicine"},{"key":"11322_CR34","doi-asserted-by":"publisher","first-page":"2453","DOI":"10.2147\/IJN.S46357","volume":"8","author":"X Gao","year":"2013","unstructured":"Gao, X. et al. Novel thermosensitive hydrogel for preventing formation of abdominal adhesions. Int. J. Nanomedicine \n                           8, 2453\u20132463 (2013).","journal-title":"Int. J. Nanomedicine"},{"key":"11322_CR35","doi-asserted-by":"publisher","DOI":"10.3390\/polym8090321","volume":"8","author":"TQM Tran","year":"2016","unstructured":"Tran, T. Q. M. et al. Bactericidal Effect of Lauric Acid-Loaded PCL-PEG-PCL Nano-Sized Micelles on Skin Commensal Propionibacterium acnes. Polymers \n                           8, 321 (2016).","journal-title":"Polymers"},{"key":"11322_CR36","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.jconrel.2007.08.030","volume":"124","author":"JS Park","year":"2007","unstructured":"Park, J. S. et al. In vitro and in vivo test of PEG\/PCL-based hydrogel scaffold for cell delivery application. J. Control Release \n                           124, 51\u201359 (2007).","journal-title":"J. Control Release"},{"key":"11322_CR37","doi-asserted-by":"publisher","DOI":"10.1038\/boneres.2015.36","volume":"4","author":"J Zhong","year":"2016","unstructured":"Zhong, J. et al. Crosstalk between adipose-derived stem cells and chondrocytes: when growth factors matter. Bone Res. \n                           4, 15036 (2016).","journal-title":"Bone Res."},{"key":"11322_CR38","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1111\/cpr.12259","volume":"49","author":"S Shi","year":"2016","unstructured":"Shi, S. et al. Effects of low oxygen tension on gene profile of soluble growth factors in co-cultured adipose-derived stromal cells and chondrocytes. Cell Prolif. \n                           49, 341\u2013351 (2016).","journal-title":"Cell Prolif."},{"key":"11322_CR39","doi-asserted-by":"publisher","DOI":"10.1038\/boneres.2015.29","volume":"3","author":"T Gong","year":"2015","unstructured":"Gong, T. et al. Nanomaterials and regenrative medicine. Bone Res. \n                           3, 15029 (2015).","journal-title":"Bone Res."},{"key":"11322_CR40","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.colsurfb.2013.01.047","volume":"106","author":"L Liu","year":"2013","unstructured":"Liu, L. et al. Camptothecine encapsulated composite drug delivery system for colorectal peritoneal carcinomatosis therapy: biodegradable microsphere in thermosensitive hydrogel. Colloids Surf. B Biointerfaces \n                           106, 93\u2013101 (2013).","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"11322_CR41","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1166\/jbmb.2014.1427","volume":"8","author":"WS Chu","year":"2014","unstructured":"Chu, W. S., Pandey, J. K. & Ahn, S. H. Fabrication of Bio-Composite Scaffold for Implantable Drug Delivery System (DDS). J. Biobased Mat. Bioenergy \n                           8, 230\u2013239 (2014).","journal-title":"J. Biobased Mat. Bioenergy"},{"key":"11322_CR42","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1016\/j.msec.2015.08.058","volume":"58","author":"L Azouz","year":"2016","unstructured":"Azouz, L., Dahmoune, F., Rezgui, F. & G\u2019Sell, C. Full factorial design optimization of anti-inflammatory drug release by PCL-PEG-PCL microspheres. Mater. Sci. Eng. C Mater. Biol. Appl. \n                           58, 412\u2013419 (2016).","journal-title":"Mater. Sci. Eng. C Mater. Biol. Appl."},{"key":"11322_CR43","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1208\/s12249-014-0198-4","volume":"16","author":"E Khodaverdi","year":"2015","unstructured":"Khodaverdi, E. et al. Injectable supramolecular hydrogel from insulin-loaded triblock PCL-PEG-PCL copolymer and gamma-cyclodextrin with sustained-release property. AAPS PharmSciTech \n                           16, 140\u2013149 (2015).","journal-title":"AAPS PharmSciTech"},{"key":"11322_CR44","doi-asserted-by":"publisher","first-page":"678","DOI":"10.1111\/cpr.12296","volume":"49","author":"S Balakrishnan","year":"2016","unstructured":"Balakrishnan, S. et al. Gold nanoparticle-conjugated quercetin inhibits epithelial-mesenchymal transition, angiogenesis and invasiveness via EGFR\/VEGFR-2-mediated pathway in breast cancer. Cell Prolif. \n                           49, 678\u2013697 (2016).","journal-title":"Cell Prolif."},{"key":"11322_CR45","doi-asserted-by":"publisher","first-page":"602","DOI":"10.1016\/j.colsurfb.2010.10.024","volume":"82","author":"H Wu","year":"2011","unstructured":"Wu, H. et al. Chitosan-polycaprolactone copolymer microspheres for transforming growth factor-\u03b21 delivery. Colloids Surf. B Biointerfaces \n                           82, 602\u2013608 (2011).","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"11322_CR46","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1038\/gt.2014.116","volume":"22","author":"H Yoshizawa","year":"2015","unstructured":"Yoshizawa, H. et al. TGF-beta(1)-siRNA delivery with nanoparticles inhibits peritoneal fibrosis. Gene Ther. \n                           22, 333\u2013340 (2015).","journal-title":"Gene Ther."},{"key":"11322_CR47","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1166\/jbn.2015.2053","volume":"11","author":"G Li","year":"2015","unstructured":"Li, G. et al. Poly(3-hydroxybutyrate-co-4-hydroxybutyrate) Based Electrospun 3D Scaffolds for Delivery of Autogeneic Chondrocytes and Adipose-Derived Stem Cells: Evaluation of Cartilage Defects in Rabbit. J. Biomed. Nanotechnol. \n                           11, 105\u2013116 (2015).","journal-title":"J. Biomed. Nanotechnol."},{"key":"11322_CR48","doi-asserted-by":"publisher","first-page":"4684","DOI":"10.1002\/jps.21780","volume":"98","author":"CY Gong","year":"2009","unstructured":"Gong, C. Y. et al. Biodegradable in situ gel-forming controlled drug delivery system based on thermosensitive PCL-PEG-PCL hydrogel: part 1\u2013Synthesis, characterization, and acute toxicity evaluation. J. Pharm. Sci. \n                           98, 4684\u20134694 (2009).","journal-title":"J. Pharm. Sci."},{"key":"11322_CR49","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1166\/jbmb.2012.1215","volume":"6","author":"Z Cui","year":"2012","unstructured":"Cui, Z. et al. Morphology and Properties of Porous and Interconnected Poly(\u03b5-caprolactone) Matrices Using Solid and Microcellular Injection Molding. J. Biobased Mat. Bioenergy \n                           6, 259\u2013268 (2012).","journal-title":"J. Biobased Mat. Bioenergy"},{"key":"11322_CR50","doi-asserted-by":"publisher","first-page":"3358","DOI":"10.1016\/j.actbio.2009.05.025","volume":"5","author":"C Gong","year":"2009","unstructured":"Gong, C. et al. Biodegradable in situ gel-forming controlled drug delivery system based on thermosensitive PCL-PEG-PCL hydrogel. Part 2: sol-gel-sol transition and drug delivery behavior. Acta Biomater. \n                           5, 3358\u20133370 (2009).","journal-title":"Acta Biomater."},{"key":"11322_CR51","doi-asserted-by":"publisher","DOI":"10.1186\/scrt427","volume":"5","author":"JY Chung","year":"2014","unstructured":"Chung, J. Y. et al. Comparison of articular cartilage repair with different hydrogel-human umbilical cord blood-derived mesenchymal stem cell composites in a rat model. Stem Cell Res. Ther. \n                           5, 39 (2014).","journal-title":"Stem Cell Res. Ther."},{"key":"11322_CR52","first-page":"22884","volume-title":"ACS Appl. Mater. Interfaces","author":"T Zhang","year":"2016","unstructured":"Zhang, T. et al. Softening Substrates Promote Chondrocytes Phenotype via RhoA\/ROCK Pathway. ACS Appl. Mater. Interfaces 8, (22884\u201322891 (2016)."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-11322-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-11322-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-11322-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T10:24:28Z","timestamp":1671791068000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-11322-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,9,5]]},"references-count":52,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,12]]}},"alternative-id":["11322"],"URL":"https:\/\/doi.org\/10.1038\/s41598-017-11322-w","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,9,5]]},"assertion":[{"value":"5 May 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 August 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 September 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"10553"}}