{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T11:04:25Z","timestamp":1785841465550,"version":"3.56.0"},"reference-count":50,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,6,17]],"date-time":"2023-06-17T00:00:00Z","timestamp":1686960000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation SNSF","doi-asserted-by":"publisher","award":["310030_197578"],"award-info":[{"award-number":["310030_197578"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Tendon injuries can result in two major drawbacks. Adhesions to the surrounding tissue may limit the range of motion, while fibrovascular scar formation can lead to poor biomechanical outcomes. Prosthetic devices may help to mitigate those problems. Emulsion electrospinning was used to develop a novel three-layer tube based on the polymer DegraPol (DP), with incorporated insulin-like growth factor-1 (IGF-1) in the middle layer. Scanning electron microscopy was utilized to assess the fiber diameter in IGF-1 containing pure DP meshes. Further characterization was performed with Fourier Transformed Infrared Spectroscopy, Differential Scanning Calorimetry, and water contact angle, as well as through the assessment of mechanical properties and release kinetics from ELISA, and the bioactivity of IGF-1 by qPCR of collagen I, ki67, and tenomodulin in rabbit Achilles tenocytes. The IGF-1-containing tubes exhibited a sustained release of the growth factor up to 4 days and showed bioactivity by significantly upregulated ki67 and tenomodulin gene expression. Moreover, they proved to be mechanically superior to pure DP tubes (significantly higher fracture strain, failure stress, and elastic modulus). The novel three-layer tubes intended to be applied over conventionally sutured tendons after a rupture may help accelerate the healing process. The release of IGF-1 stimulates proliferation and matrix synthesis of cells at the repair site. In addition, adhesion formation to surrounding tissue can be reduced due to the physical barrier.<\/jats:p>","DOI":"10.3390\/ijms241210272","type":"journal-article","created":{"date-parts":[[2023,6,19]],"date-time":"2023-06-19T01:31:14Z","timestamp":1687138274000},"page":"10272","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Bioactive and Elastic Emulsion Electrospun DegraPol Tubes Delivering IGF-1 for Tendon Rupture Repair"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9295-4658","authenticated-orcid":false,"given":"Julia","family":"Rieber","sequence":"first","affiliation":[{"name":"Division of Plastic Surgery and Hand Surgery, University Hospital Zurich, Sternwartstrasse 14, 8091 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5497-4797","authenticated-orcid":false,"given":"Gabriella","family":"Meier-B\u00fcrgisser","sequence":"additional","affiliation":[{"name":"Division of Plastic Surgery and Hand Surgery, University Hospital Zurich, Sternwartstrasse 14, 8091 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4448-8269","authenticated-orcid":false,"given":"Iris","family":"Miescher","sequence":"additional","affiliation":[{"name":"Division of Plastic Surgery and Hand Surgery, University Hospital Zurich, Sternwartstrasse 14, 8091 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1670-2296","authenticated-orcid":false,"given":"Franz E.","family":"Weber","sequence":"additional","affiliation":[{"name":"Oral Biotechnology & Bioengineering, Center for Dental Medicine, Cranio-Maxillofacial and Oral Surgery, University of Zurich, 8032 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9978-1438","authenticated-orcid":false,"given":"Petra","family":"Wolint","sequence":"additional","affiliation":[{"name":"Division of Plastic Surgery and Hand Surgery, University Hospital Zurich, Sternwartstrasse 14, 8091 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Health Sciences & Technology & Department of Materials, Schmelzbergstrasse 9, LFO, 8092 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esteban","family":"Ongini","sequence":"additional","affiliation":[{"name":"Orthopaedic Biomechanics, University Clinic Balgrist, Forchstrasse 340, 8008 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0049-1255","authenticated-orcid":false,"given":"Athanasios","family":"Milionis","sequence":"additional","affiliation":[{"name":"Laboratory of Thermodynamics in Emerging Technologies, Department of Mechanical and Process Engineering, ETH Zurich, 8092 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jess G.","family":"Snedeker","sequence":"additional","affiliation":[{"name":"Orthopaedic Biomechanics, University Clinic Balgrist, Forchstrasse 340, 8008 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4372-0561","authenticated-orcid":false,"given":"Maurizio","family":"Calcagni","sequence":"additional","affiliation":[{"name":"Division of Plastic Surgery and Hand Surgery, University Hospital Zurich, Sternwartstrasse 14, 8091 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7919-7448","authenticated-orcid":false,"given":"Johanna","family":"Buschmann","sequence":"additional","affiliation":[{"name":"Division of Plastic Surgery and Hand Surgery, University Hospital Zurich, Sternwartstrasse 14, 8091 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1002\/bdrc.21041","article-title":"Tendon and ligament regeneration and repair: Clinical relevance and developmental paradigm","volume":"99","author":"Yang","year":"2013","journal-title":"Birth Defects Res. C Embryo Today"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"312","DOI":"10.4103\/0970-0358.118611","article-title":"Avoidance of unfavourable results following primary flexor tendon surgery","volume":"46","author":"Elliot","year":"2013","journal-title":"Indian J. Plast. Surg."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1146\/annurev-bioeng-071811-150122","article-title":"Tendon Healing: Repair and Regeneration","volume":"14","author":"Voleti","year":"2012","journal-title":"Annu. Rev. Biomed. Eng."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1007\/s11751-011-0124-1","article-title":"The repair of the Achilles tendon rupture: Comparison of two percutaneous techniques","volume":"6","author":"Aldegheri","year":"2011","journal-title":"Strat. Trauma Limb Reconstr."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1002\/jor.24475","article-title":"Tendon and Ligament Healing and Current Approaches to Tendon and Ligament Regeneration","volume":"38","author":"Leong","year":"2020","journal-title":"J. Orthop. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3228","DOI":"10.1002\/jbm.a.34633","article-title":"New concept for a regenerative and resorbable prosthesis for tendon and ligament: Physicochemical and biological characterization of PLA-braided biomaterial","volume":"101","author":"Santos","year":"2013","journal-title":"J. Biomed. Mater. Res. Part A"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1002\/jor.24205","article-title":"Regenerative rehabilitation: The role of mechanotransduction in orthopaedic regenerative medicine","volume":"37","author":"Glatt","year":"2019","journal-title":"J. Orthop. Res."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Chen, Y., Jiang, L., Lyu, K., Lu, J., Long, L., Wang, X., Liu, T., and Li, S. (2022). A Promising Candidate in Tendon Healing Events-PDGF-BB. Biomolecules, 12.","DOI":"10.3390\/biom12101518"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"119722","DOI":"10.1016\/j.biomaterials.2019.119722","article-title":"Elastic and surgeon friendly electrospun tubes delivering PDGF-BB positively impact tendon rupture healing in a rabbit Achilles tendon model","volume":"232","author":"Evrova","year":"2020","journal-title":"Biomaterials"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1080\/08977194.2022.2082294","article-title":"Transforming growth factor-\u03b2 signalling pathway in tendon healing","volume":"40","author":"Li","year":"2022","journal-title":"Growth Factors"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1002\/jor.21301","article-title":"Sustained delivery of transforming growth factor beta three enhances tendon-to-bone healing in a rat model","volume":"29","author":"Manning","year":"2011","journal-title":"J. Orthop. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e1701393","DOI":"10.1002\/adhm.201701393","article-title":"Tough Composite Hydrogels with High Loading and Local Release of Biological Drugs","volume":"7","author":"Li","year":"2018","journal-title":"Adv. Healthc. Mater."},{"key":"ref_13","first-page":"67","article-title":"GH and IGF-1 Replacement in Children","volume":"Volume 261","author":"Kiess","year":"2020","journal-title":"Handbook of Experimental Pharmacology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1159\/000445173","article-title":"Growth Hormone and Insulin-Like Growth Factor-1","volume":"Volume 47","author":"Nicholls","year":"2016","journal-title":"Frontiers of Hormone Research"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Yoshida, T., and Delafontaine, P. (2020). Mechanisms of IGF-1-Mediated Regulation of Skeletal Muscle Hypertrophy and Atrophy. Cells, 9.","DOI":"10.3390\/cells9091970"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1097\/PRS.0b013e31823aeb94","article-title":"Optimization of Human Tendon Tissue Engineering: Synergistic Effects of Growth Factors for Use in Tendon Scaffold Repopulation","volume":"129","author":"Raghavan","year":"2012","journal-title":"Plast. Reconstr. Surg."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Miescher, I., Rieber, J., Calcagni, M., and Buschmann, J. (2023). In Vitro and In Vivo Effects of IGF-1 Delivery Strategies on Tendon Healing: A Review. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24032370"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1177\/03635465990270031701","article-title":"Insulin-like growth factor I accelerates functional recovery from Achilles tendon injury in a rat model","volume":"27","author":"Kurtz","year":"1999","journal-title":"Am. J. Sport. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.1002\/jbm.a.37378","article-title":"Pegylated insulin-like growth factor-1 biotherapeutic delivery promotes rotator cuff regeneration in a rat model","volume":"110","author":"Prabhath","year":"2022","journal-title":"J. Biomed. Mater. Res. Part A"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1016\/S0736-0266(02)00009-8","article-title":"Insulin-like growth factor-I improves cellular and molecular aspects of healing in a collagenase-induced model of flexor tendinitis","volume":"20","author":"Dahlgren","year":"2002","journal-title":"J. Orthop. Res."},{"key":"ref_21","first-page":"380","article-title":"Effect of combined administration of Transforming Growth Factor-b1 and Insulin-like Growth Factor I on the mechanical properties of a patellar tendon defect model in rabbits","volume":"76","author":"Lyras","year":"2010","journal-title":"Acta Orthop. Belg."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1016\/j.jgr.2021.08.005","article-title":"Ginsenoside Rg1 enhances the healing of injured tendon in achilles tendinitis through the activation of IGF1R signaling mediated by oestrogen receptor","volume":"46","author":"Wu","year":"2022","journal-title":"J. Ginseng Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1002\/mabi.201500455","article-title":"Bioactive, Elastic, and Biodegradable Emulsion Electrospun DegraPol Tube Delivering PDGF-BB for Tendon Rupture Repair","volume":"16","author":"Evrova","year":"2016","journal-title":"Macromol. Biosci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"45","DOI":"10.14712\/fb2022068020045","article-title":"Time and Temperature Stability of TGF-\u03b21, EGF and IGF-1 in 20% and 100% Human Serum","volume":"68","author":"Jirsova","year":"2022","journal-title":"Folia Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1002\/term.1624","article-title":"Synthesis, characterization and histomorphometric analysis of cellular response to a new elastic DegraPol (R) polymer for rabbit Achilles tendon rupture repair","volume":"9","author":"Buschmann","year":"2015","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.cpm.2022.07.006","article-title":"Achilles Tendon Rupture Repair: Simple to Complex","volume":"40","author":"King","year":"2023","journal-title":"Clin. Podiatr. Med. Surg."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1302\/2046-3758.118.BJR-2021-0576.R1","article-title":"Tendon healing: A concise review on cellular and molecular mechanisms with a particular focus on the Achilles tendon","volume":"11","author":"Stange","year":"2022","journal-title":"Bone Joint Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1055\/s-0041-1731632","article-title":"Tendon: Principles of Healing and Repair","volume":"35","author":"Chartier","year":"2021","journal-title":"Semin. Plast. Surg."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.fcl.2021.11.026","article-title":"Achilles: Failed Acute Repair","volume":"27","author":"Parekh","year":"2022","journal-title":"Foot Ankle Clin."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"23293","DOI":"10.1038\/s41598-021-02780-4","article-title":"Electrospun tube reduces adhesion in rabbit Achilles tendon 12 weeks post-surgery without PAR-2 overexpression","volume":"11","author":"Evrova","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"153","DOI":"10.2460\/ajvr.73.1.153","article-title":"Comparison of equine tendon- and bone marrow-derived cells cultured on tendon matrix with or without insulin-like growth factor-I supplementation","volume":"73","author":"Durgam","year":"2012","journal-title":"Am. J. Vet. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.ghir.2014.09.001","article-title":"Insulin-like growth factor I enhances collagen synthesis in engineered human tendon tissue","volume":"25","author":"Herchenhan","year":"2015","journal-title":"Growth Horm. IGF Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1937","DOI":"10.1089\/ten.2006.12.1937","article-title":"Tissue engineering of flexor tendons: Optimization of tenocyte proliferation using growth factor supplementation","volume":"12","author":"Costa","year":"2006","journal-title":"Tissue Eng."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1177\/1558944715628005","article-title":"Optimized Repopulation of Tendon Hydrogel: Synergistic Effects of Growth Factor Combinations and Adipose-Derived Stem Cells","volume":"12","author":"Farnebo","year":"2017","journal-title":"Hand"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"6053","DOI":"10.1021\/acsbiomaterials.0c01228","article-title":"Phenomenology of the Initial Burst Release of Drugs from PLGA Microparticles","volume":"6","author":"Yoo","year":"2020","journal-title":"ACS Biomater. Sci. Eng."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Akhmetova, A., and Heinz, A. (2020). Electrospinning Proteins for Wound Healing Purposes: Opportunities and Challenges. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13010004"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1814","DOI":"10.1002\/adma.200701630","article-title":"Emulsion as a Means of Controlling Electrospinning of Polymers","volume":"21","author":"Sy","year":"2009","journal-title":"Adv. Mater."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"123993","DOI":"10.1016\/j.ijbiomac.2023.123993","article-title":"Encapsulation of lycopene into electrospun nanofibers from whey protein isolate-Tricholoma lobayense polysaccharide complex stabilized emulsions: Structural characterization, storage stability, in vitro release, and cellular evaluation","volume":"238","author":"Chen","year":"2023","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2375","DOI":"10.2147\/IJN.S15586","article-title":"Manufacturing of biodegradable polyurethane scaffolds based on polycaprolactone using a phase separation method: Physical properties and in vitro assay","volume":"6","author":"Asefnejad","year":"2011","journal-title":"Int. J. Nanomed."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Saad, B., Kuboki, Y., Welti, M., Uhlschmid, G.K., Neuenschwander, P., and Suter, U.W. (1999, January 3\u20136). DegraPol-Foam: A degradable and highly porous polyesterurethane foam as a new substrate for bone formation. Proceedings of the 12th World Congress of the International-Society-for-Artificial-Organs\/26th Congress of the European-Society-for-Artificial-Organs, Edinburgh, UK.","DOI":"10.1046\/j.1525-1594.2000.06664.x"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1021\/ed039p546","article-title":"Spectrometric Identification of Organic Compounds","volume":"39","author":"Silverstein","year":"1962","journal-title":"J. Chem. Educ."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1007\/s00396-012-2796-6","article-title":"Contact angle hysteresis: A review of fundamentals and applications","volume":"291","author":"Eral","year":"2013","journal-title":"Colloid Polym. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1002\/1521-3935(20000701)201:11<1067::AID-MACP1067>3.0.CO;2-Y","article-title":"Hydroxy-telechelic copolyesters with well defined sequence structure through ring-opening polymerization","volume":"201","author":"Lendlein","year":"2000","journal-title":"Macromol. Chem. Phys."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2017","DOI":"10.1021\/bm0501149","article-title":"Sustained Release of Proteins from Electrospun Biodegradable Fibers","volume":"6","author":"Chew","year":"2005","journal-title":"Biomacromolecules"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1166\/jbn.2011.1342","article-title":"Induction of Cell Migration In Vitro by an Electrospun PDGF-BB\/PLGA\/PEG-PLA Nanofibrous Scaffold","volume":"7","author":"Zhao","year":"2011","journal-title":"J. Biomed. Nanotechnol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"15117","DOI":"10.1038\/s41598-019-51513-1","article-title":"Impact of UV sterilization and short term storage on the in vitro release kinetics and bioactivity of biomolecules from electrospun scaffolds","volume":"9","author":"Evrova","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1089\/ten.tea.2012.0497","article-title":"Composite Growth Factor Supplementation Strategies to Enhance Tenocyte Bioactivity in Aligned Collagen-GAG Scaffolds","volume":"19","author":"Caliari","year":"2013","journal-title":"Tissue Eng. Part A"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"215","DOI":"10.11138\/mltj\/2017.7.2.215","article-title":"Lactoferrin and parathyroid hormone are not harmful to primary tenocytes in vitro, but PDGF may be","volume":"7","author":"Musson","year":"2017","journal-title":"Muscles Ligaments Tendons J."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Miescher, I., Wolint, P., Opelz, C., Snedeker, J.G., Giovanoli, P., Calcagni, M., and Buschmann, J. (2022). Impact of High-Molecular-Weight Hyaluronic Acid on Gene Expression in Rabbit Achilles Tenocytes In Vitro. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23147926"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"44722","DOI":"10.1021\/acsami.8b16307","article-title":"Nanozymes in Nanofibrous Mats with Haloperoxidase-like Activity to Combat Biofouling","volume":"10","author":"Hu","year":"2018","journal-title":"ACS Appl. Mater. Interfaces"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/12\/10272\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:55:32Z","timestamp":1760126132000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/12\/10272"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,17]]},"references-count":50,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2023,6]]}},"alternative-id":["ijms241210272"],"URL":"https:\/\/doi.org\/10.3390\/ijms241210272","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,17]]}}}