{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T12:40:08Z","timestamp":1793968808546,"version":"4.8.0"},"reference-count":85,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2020,3,1]],"date-time":"2020-03-01T00:00:00Z","timestamp":1583020800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,3,1]],"date-time":"2020-03-01T00:00:00Z","timestamp":1583020800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2019,11,11]],"date-time":"2019-11-11T00:00:00Z","timestamp":1573430400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Biomaterials"],"published-print":{"date-parts":[[2020,3]]},"DOI":"10.1016\/j.biomaterials.2019.119591","type":"journal-article","created":{"date-parts":[[2019,11,5]],"date-time":"2019-11-05T12:59:22Z","timestamp":1572958762000},"page":"119591","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":76,"special_numbering":"C","title":["Oral delivery of novel human IGF-1 bioencapsulated in lettuce cells promotes musculoskeletal cell proliferation, differentiation and diabetic fracture healing"],"prefix":"10.1016","volume":"233","author":[{"given":"J.","family":"Park","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.-C.","family":"Kwon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.A.","family":"Gonnella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Daniell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.biomaterials.2019.119591_bib1","first-page":"10","article-title":"Equivalent recombinant human insulin preparations and their place in therapy","volume":"11","author":"Sandow","year":"2015","journal-title":"Eur. Endocrinol."},{"key":"10.1016\/j.biomaterials.2019.119591_bib2","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1146\/annurev-genet-120215-035349","article-title":"Vaccination via chloroplast genetics: affordable protein drugs for the prevention and treatment of inherited or infectious human diseases","volume":"50","author":"Daniell","year":"2016","journal-title":"Annu. Rev. Genet."},{"key":"10.1016\/j.biomaterials.2019.119591_bib3","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1111\/pbi.12366","article-title":"Plant-based oral delivery of beta-glucocerebrosidase as an enzyme replacement therapy for Gaucher's disease","volume":"13","author":"Shaaltiel","year":"2015","journal-title":"Plant Biotechnol. J."},{"key":"10.1016\/j.biomaterials.2019.119591_bib4","doi-asserted-by":"crossref","first-page":"499","DOI":"10.4155\/pbp.14.32","article-title":"On the way to commercializing plant cell culture platform for biopharmaceuticals: present status and prospect","volume":"2","author":"Xu","year":"2014","journal-title":"Pharm. Bioprocess."},{"key":"10.1016\/j.biomaterials.2019.119591_bib5","article-title":"Taliglucerase (Elelyso) for Gaucher disease","volume":"54","year":"2012","journal-title":"Med. Lett. Drugs Ther."},{"key":"10.1016\/j.biomaterials.2019.119591_bib6","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.biomaterials.2015.08.004","article-title":"Low cost industrial production of coagulation factor IX bioencapsulated in lettuce cells for oral tolerance induction in hemophilia B","volume":"70","author":"Su","year":"2015","journal-title":"Biomaterials"},{"key":"10.1016\/j.biomaterials.2019.119591_bib7","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1016\/j.ymthe.2016.11.009","article-title":"Oral tolerance induction in hemophilia B dogs fed with transplastomic lettuce","volume":"25","author":"Herzog","year":"2017","journal-title":"Mol. Ther."},{"key":"10.1016\/j.biomaterials.2019.119591_bib8","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1038\/mt.2016.115","article-title":"Oral delivery of protein drugs bioencapsulated in plant cells","volume":"24","author":"Kwon","year":"2016","journal-title":"Mol. Ther."},{"key":"10.1016\/j.biomaterials.2019.119591_bib9","doi-asserted-by":"crossref","DOI":"10.1016\/j.biotechadv.2019.06.012","article-title":"Plant cell-made protein antigens for induction of Oral tolerance","author":"Daniell","year":"2019","journal-title":"Biotechnol. Adv."},{"key":"10.1016\/j.biomaterials.2019.119591_bib10","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.anai.2018.06.005","article-title":"FDA-approved peanut allergy treatment the first wave is about to crest","volume":"121","author":"Tilles","year":"2018","journal-title":"Ann. Allergy Asthma Immunol."},{"key":"10.1016\/j.biomaterials.2019.119591_bib11","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.bone.2015.04.036","article-title":"Role of IGF-I signaling in muscle bone interactions","volume":"80","author":"Bikle","year":"2015","journal-title":"Bone"},{"key":"10.1016\/j.biomaterials.2019.119591_bib12","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1001\/archneurol.2010.227","article-title":"Open-label trial of recombinant human insulin-like growth factor 1\/recombinant human insulin-like growth factor binding protein 3 in myotonic dystrophy type 1","volume":"68","author":"Heatwole","year":"2011","journal-title":"Arch. Neurol."},{"key":"10.1016\/j.biomaterials.2019.119591_bib13","doi-asserted-by":"crossref","first-page":"5706","DOI":"10.1210\/en.2007-0608","article-title":"Conditional deletion of insulin-like growth factor-I in collagen type 1 alpha 2-expressing cells results in postnatal lethality and a dramatic reduction in bone accretion","volume":"148","author":"Govoni","year":"2007","journal-title":"Endocrinology"},{"key":"10.1016\/j.biomaterials.2019.119591_bib14","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1016\/j.bone.2006.02.068","article-title":"Transgenic mice with osteoblast-targeted insulin-like growth factor-I show increased bone remodeling","volume":"39","author":"Jiang","year":"2006","journal-title":"Bone"},{"key":"10.1016\/j.biomaterials.2019.119591_bib15","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.1007\/s00198-007-0430-0","article-title":"Serum insulin-like growth factor-I level is associated with the presence of vertebral fractures in postmenopausal women with type 2 diabetes mellitus","volume":"18","author":"Kanazawa","year":"2007","journal-title":"Osteoporos. Int."},{"key":"10.1016\/j.biomaterials.2019.119591_bib16","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1359\/jbmr.1997.12.8.1272","article-title":"Serum levels of insulin-like growth factor (IGF) I, IGF-binding protein (IGFBP)-2, and IGFBP-3 in osteoporotic patients with and without spinal fractures","volume":"12","author":"Sugimoto","year":"1997","journal-title":"J. Bone Miner. Res."},{"key":"10.1016\/j.biomaterials.2019.119591_bib17","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/S8756-3282(02)00798-6","article-title":"Improvement of fracture healing by systemic administration of growth hormone and local application of insulin-like growth factor-1 and transforming growth factor-beta1","volume":"31","author":"Schmidmaier","year":"2002","journal-title":"Bone"},{"key":"10.1016\/j.biomaterials.2019.119591_bib18","first-page":"235060","article-title":"Effect of GH\/IGF-1 on bone metabolism and osteoporsosis","volume":"2014","author":"Locatelli","year":"2014","journal-title":"Internet J. Endocrinol."},{"key":"10.1016\/j.biomaterials.2019.119591_bib19","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/S1995-7645(13)60195-9","article-title":"Expression of FGF-2 and IGF-1 in diabetic rats with fracture","volume":"7","author":"Chen","year":"2014","journal-title":"Asian Pac. J. Trop. Med."},{"key":"10.1016\/j.biomaterials.2019.119591_bib20","doi-asserted-by":"crossref","first-page":"6","DOI":"10.3389\/fendo.2013.00006","article-title":"Anabolic effects of IGF-1 signaling on the skeleton","volume":"4","author":"Tahimic","year":"2013","journal-title":"Front Endocrinol. (Lausanne)"},{"key":"10.1016\/j.biomaterials.2019.119591_bib21","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/j.scr.2011.12.005","article-title":"Insulin-like growth factor 1 can promote the osteogenic differentiation and osteogenesis of stem cells from apical papilla","volume":"8","author":"Wang","year":"2012","journal-title":"Stem Cell Res."},{"key":"10.1016\/j.biomaterials.2019.119591_bib22","doi-asserted-by":"crossref","first-page":"202","DOI":"10.2119\/molmed.2014.00011","article-title":"The complexity of the IGF1 gene splicing, posttranslational modification and bioactivity","volume":"20","author":"Philippou","year":"2014","journal-title":"Mol. Med."},{"key":"10.1016\/j.biomaterials.2019.119591_bib23","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1210\/en.2012-1992","article-title":"The pro-forms of insulin-like growth factor I (IGF-I) are predominant in skeletal muscle and alter IGF-I receptor activation","volume":"154","author":"Durzynska","year":"2013","journal-title":"Endocrinology"},{"key":"10.1016\/j.biomaterials.2019.119591_bib24","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.ghir.2014.06.003","article-title":"Optimizing IGF-I for skeletal muscle therapeutics","volume":"24","author":"Philippou","year":"2014","journal-title":"Growth Hormone IGF Res."},{"key":"10.1016\/j.biomaterials.2019.119591_bib25","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1152\/japplphysiol.01308.2009","article-title":"The insulin-like growth factor (IGF)-I E-peptides are required for isoform-specific gene expression and muscle hypertrophy after local IGF-I production","volume":"108","author":"Barton","year":"2010","journal-title":"J. Appl. Physiol."},{"key":"10.1016\/j.biomaterials.2019.119591_bib26","doi-asserted-by":"crossref","first-page":"1474","DOI":"10.1104\/pp.109.139816","article-title":"Plant physiological adaptations to the massive foreign protein synthesis occurring in recombinant chloroplasts","volume":"150","author":"Bally","year":"2009","journal-title":"Plant Physiol."},{"key":"10.1016\/j.biomaterials.2019.119591_bib27","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.cbpa.2017.02.007","article-title":"Expression and functional evaluation of biopharmaceuticals made in plant chloroplasts","volume":"38","author":"Zhang","year":"2017","journal-title":"Curr. Opin. Chem. Biol."},{"key":"10.1016\/j.biomaterials.2019.119591_bib28","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1111\/j.1467-7652.2011.00608.x","article-title":"Tobacco plastidial thioredoxins as modulators of recombinant protein production in transgenic chloroplasts","volume":"9","author":"Sanz-Barrio","year":"2011","journal-title":"Plant Biotechnol. J"},{"key":"10.1016\/j.biomaterials.2019.119591_bib29","doi-asserted-by":"crossref","first-page":"1862","DOI":"10.1016\/j.peptides.2008.07.014","article-title":"A biologically active rhIGF-1 fusion accumulated in transgenic rice seeds can reduce blood glucose in diabetic mice via oral delivery","volume":"29","author":"Xie","year":"2008","journal-title":"Peptides"},{"key":"10.1016\/j.biomaterials.2019.119591_bib30","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/1472-6750-9-33","article-title":"Optimization of codon composition and regulatory elements for expression of human insulin like growth factor-1 in transgenic chloroplasts and evaluation of structural identity and function","volume":"9","author":"Daniell","year":"2009","journal-title":"BMC Biotechnol."},{"key":"10.1016\/j.biomaterials.2019.119591_bib31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ghir.2017.07.003","article-title":"Recombinant human IGF-1 produced by transgenic plant cell suspension culture enhances new bone formation in calvarial defects","volume":"36","author":"Poudel","year":"2017","journal-title":"Growth Hormone IGF Res."},{"key":"10.1016\/j.biomaterials.2019.119591_bib32","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/s11248-019-00116-7","article-title":"Evaluation of lettuce chloroplast and soybean cotyledon as platforms for production of functional bone morphogenetic protein 2","volume":"28","author":"Queiroz","year":"2019","journal-title":"Transgenic Res."},{"key":"10.1016\/j.biomaterials.2019.119591_bib33","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1104\/pp.16.00981","article-title":"Codon optimization to enhance expression yields insights into chloroplast translation","volume":"172","author":"Kwon","year":"2016","journal-title":"Plant Physiol."},{"key":"10.1016\/j.biomaterials.2019.119591_bib34","doi-asserted-by":"crossref","first-page":"17566","DOI":"10.1074\/jbc.270.29.17566","article-title":"Mutational analysis of the Insulin-like Growth-Factor-I prohormone precessing site","volume":"270","author":"Duguay","year":"1995","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.biomaterials.2019.119591_bib35","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1096\/fj.05-5134fje","article-title":"Receptor-mediated oral delivery of a bioencapsulated green fluorescent protein expressed in transgenic chloroplasts into the mouse circulatory system","volume":"20","author":"Limaye","year":"2006","journal-title":"FASEB J."},{"key":"10.1016\/j.biomaterials.2019.119591_bib36","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1007\/s00018-008-7496-5","article-title":"Cholera toxin structure, gene regulation and pathophysiological and immunological aspects","volume":"65","author":"Sanchez","year":"2008","journal-title":"Cell. Mol. Life Sci."},{"key":"10.1016\/j.biomaterials.2019.119591_bib37","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1111\/pbi.13119","article-title":"Validation of leaf and microbial pectinases: commercial launching of a new platform technology","volume":"17","author":"Daniell","year":"2019","journal-title":"Plant Biotechnol. J."},{"key":"10.1016\/j.biomaterials.2019.119591_bib38","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1111\/pbi.13122","article-title":"Validation of leaf enzymes in the detergent and textile industries: launching of a new platform technology","volume":"17","author":"Kumari","year":"2019","journal-title":"Plant Biotechnol. J."},{"key":"10.1016\/j.biomaterials.2019.119591_bib39","doi-asserted-by":"crossref","first-page":"R1085","DOI":"10.1152\/ajpregu.1996.270.5.R1085","article-title":"Orally administered IGF-I increases intestinal mucosal growth in formula-fed neonatal pigs","volume":"270","author":"Burrin","year":"1996","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"10.1016\/j.biomaterials.2019.119591_bib40","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1046\/j.1523-1755.2000.00886.x","article-title":"Recombinant human insulin-like growth factor-1 induces an anabolic response in malnourished CAPD patients","volume":"57","author":"Fouque","year":"2000","journal-title":"Kidney Int."},{"key":"10.1016\/j.biomaterials.2019.119591_bib41","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.biomaterials.2015.11.051","article-title":"Low cost delivery of proteins bioencapsulated in plant cells to human non-immune or immune modulatory cells","volume":"80","author":"Xiao","year":"2016","journal-title":"Biomaterials"},{"key":"10.1016\/j.biomaterials.2019.119591_bib42","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1038\/nrmicro1817","article-title":"Polysaccharide utilization by gut bacteria: potential for new insights from genomic analysis","volume":"6","author":"Flint","year":"2008","journal-title":"Nat. Rev. Microbiol."},{"key":"10.1016\/j.biomaterials.2019.119591_bib43","doi-asserted-by":"crossref","DOI":"10.1161\/HYPERTENSIONAHA.114.03871","article-title":"Oral delivery of angiotensin-converting enzyme 2 and angiotensin-(1-7) bioencapsulated in plant cells attenuates pulmonary hypertension","volume":"64","author":"Shenoy","year":"2014","journal-title":"Hypertension"},{"key":"10.1016\/j.biomaterials.2019.119591_bib44","doi-asserted-by":"crossref","first-page":"2069","DOI":"10.1038\/mt.2014.179","article-title":"Oral delivery of ACE2\/Ang-(1-7) bioencapsulated in plant cells protects against experimental uveitis and autoimmune uveoretinitis","volume":"22","author":"Shil","year":"2014","journal-title":"Mol. Ther."},{"key":"10.1016\/j.biomaterials.2019.119591_bib45","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1111\/pbi.12008","article-title":"Oral delivery of bioencapsulated exendin-4 expressed in chloroplasts lowers blood glucose level in mice and stimulates insulin secretion in beta-TC6 cells","volume":"11","author":"Kwon","year":"2013","journal-title":"Plant Biotechnol. J."},{"key":"10.1016\/j.biomaterials.2019.119591_bib46","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1111\/j.1467-7652.2010.00582.x","article-title":"Low-cost production of proinsulin in tobacco and lettuce chloroplasts for injectable or oral delivery of functional insulin and C-peptide","volume":"9","author":"Boyhan","year":"2011","journal-title":"Plant Biotechnol. J."},{"key":"10.1016\/j.biomaterials.2019.119591_bib47","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1111\/pbi.12859","article-title":"Expression and assembly of largest foreign protein in chloroplasts: oral delivery of human FVIII made in lettuce chloroplasts robustly suppresses inhibitor formation in haemophilia A mice","volume":"16","author":"Kwon","year":"2017","journal-title":"Plant Biotechnol. J"},{"key":"10.1016\/j.biomaterials.2019.119591_bib48","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1182\/blood-2013-10-528737","article-title":"Suppression of inhibitor formation against FVIII in a murine model of hemophilia A by oral delivery of antigens bioencapsulated in plant cells","volume":"124","author":"Sherman","year":"2014","journal-title":"Blood"},{"key":"10.1016\/j.biomaterials.2019.119591_bib49","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1111\/pbi.12413","article-title":"Oral delivery of Acid Alpha Glucosidase epitopes expressed in plant chloroplasts suppresses antibody formation in treatment of Pompe mice","volume":"13","author":"Su","year":"2015","journal-title":"Plant Biotechnol. J"},{"key":"10.1016\/j.biomaterials.2019.119591_bib50","doi-asserted-by":"crossref","first-page":"2418","DOI":"10.1182\/blood-2014-08-597070","article-title":"Plant-based oral tolerance to hemophilia therapy employs a complex immune regulatory response including LAP+CD4+ T cells","volume":"125","author":"Wang","year":"2015","journal-title":"Blood"},{"key":"10.1016\/j.biomaterials.2019.119591_bib51","doi-asserted-by":"crossref","first-page":"3640","DOI":"10.1128\/IAI.00050-08","article-title":"Effective plague vaccination via oral delivery of plant cells expressing F1-V antigens in chloroplasts","volume":"76","author":"Arlen","year":"2008","journal-title":"Infect. Immun."},{"key":"10.1016\/j.biomaterials.2019.119591_bib52","doi-asserted-by":"crossref","first-page":"2190","DOI":"10.1111\/pbi.12575","article-title":"Cold chain and virus-free chloroplast-made booster vaccine to confer immunity against different poliovirus serotypes","volume":"14","author":"Chan","year":"2016","journal-title":"Plant Biotechnol. J"},{"key":"10.1016\/j.biomaterials.2019.119591_bib53","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1006\/jmbi.2001.4921","article-title":"Expression of the native cholera toxin B subunit gene and assembly as functional oligomers in transgenic tobacco chloroplasts","volume":"311","author":"Daniell","year":"2001","journal-title":"J. Mol. Biol."},{"key":"10.1016\/j.biomaterials.2019.119591_bib54","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1111\/pbi.13060","article-title":"Cold chain and virus-free oral polio booster vaccine made in lettuce chloroplasts confers protection against all three poliovirus serotypes","volume":"17","author":"Daniell","year":"2019","journal-title":"Plant Biotechnol. J"},{"key":"10.1016\/j.biomaterials.2019.119591_bib55","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1111\/j.1467-7652.2009.00479.x","article-title":"Chloroplast-derived vaccine antigens confer dual immunity against cholera and malaria by oral or injectable delivery","volume":"8","author":"Davoodi-Semiromi","year":"2010","journal-title":"Plant Biotechnol. J"},{"key":"10.1016\/j.biomaterials.2019.119591_bib56","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1007\/s11103-011-9766-0","article-title":"Expression of dengue-3 premembrane and envelope polyprotein in lettuce chloroplasts","volume":"76","author":"Kanagaraj","year":"2011","journal-title":"Plant Mol. Biol."},{"key":"10.1016\/j.biomaterials.2019.119591_bib57","doi-asserted-by":"crossref","first-page":"8266","DOI":"10.1128\/IAI.73.12.8266-8274.2005","article-title":"Plant-based vaccine: mice immunized with chloroplast-derived anthrax protective antigen survive anthrax lethal toxin challenge","volume":"73","author":"Koya","year":"2005","journal-title":"Infect. Immun."},{"key":"10.1016\/j.biomaterials.2019.119591_bib58","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0054708","article-title":"Low cost tuberculosis vaccine antigens in capsules: expression in chloroplasts, bio-encapsulation, stability and functional evaluation in vitro","volume":"8","author":"Lakshmi","year":"2013","journal-title":"PLoS One"},{"issue":"31\u201332","key":"10.1016\/j.biomaterials.2019.119591_bib59","doi-asserted-by":"crossref","first-page":"4374","DOI":"10.1016\/j.vaccine.2004.01.069","article-title":"Expression of Bacillus anthracis protective antigen in transgenic chloroplasts of tobacco, a non-food\/feed crop","volume":"22","author":"Watson","year":"2004","journal-title":"Vaccine"},{"key":"10.1016\/j.biomaterials.2019.119591_bib60","doi-asserted-by":"crossref","first-page":"5418","DOI":"10.1016\/j.vaccine.2016.12.061","article-title":"Long-term evaluation of mucosal and systemic immunity and protection conferred by different polio booster vaccines","volume":"35","author":"Xiao","year":"2017","journal-title":"Vaccine"},{"issue":"7","key":"10.1016\/j.biomaterials.2019.119591_bib61","doi-asserted-by":"crossref","first-page":"2520","DOI":"10.1073\/pnas.72.7.2520","article-title":"Interaction of cholera toxin and membrane GM1 ganglioside of small intestine","volume":"72","author":"Holmgren","year":"1975","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.biomaterials.2019.119591_bib62","doi-asserted-by":"crossref","first-page":"681","DOI":"10.3109\/00365521.2014.898326","article-title":"Surface area of the digestive tract - revisited","volume":"49","author":"Helander","year":"2014","journal-title":"Scand. J. Gastroenterol."},{"key":"10.1016\/j.biomaterials.2019.119591_bib63","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1111\/j.1467-7652.2007.00259.x","article-title":"Expression of cholera toxin B-proinsulin fusion protein in lettuce and tobacco chloroplasts - oral administration protects against development of insulitis in non-obese diabetic mice","volume":"5","author":"Ruhlman","year":"2007","journal-title":"Plant Biotechnol. J."},{"key":"10.1016\/j.biomaterials.2019.119591_bib64","series-title":"The Hypothalamus and Pituitary Part II: the Anterior Pituitary, the Endocrine System","first-page":"39","author":"Hinson","year":"2010"},{"key":"10.1016\/j.biomaterials.2019.119591_bib65","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.1002\/stem.697","article-title":"Mesenchymal stem cells expressing insulin-like growth factor-I (MSCIGF) promote fracture healing and restore new bone formation in Irs1 knockout mice: analyses of MSCIGF autocrine and paracrine regenerative effects","volume":"29","author":"Granero-Molto","year":"2011","journal-title":"Stem Cells"},{"key":"10.1016\/j.biomaterials.2019.119591_bib66","doi-asserted-by":"crossref","first-page":"230","DOI":"10.3109\/08977194.2012.683188","article-title":"Systemically delivered insulin-like growth factor-I enhances mesenchymal stem cell-dependent fracture healing","volume":"30","author":"Myers","year":"2012","journal-title":"Growth Factors"},{"key":"10.1016\/j.biomaterials.2019.119591_bib67","doi-asserted-by":"crossref","DOI":"10.3390\/ijms19040944","article-title":"Mesenchymal stem cells of dental origin for inducing tissue regeneration in periodontitis: a mini-review","volume":"19","author":"Hernandez-Monjaraz","year":"2018","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.biomaterials.2019.119591_bib68","article-title":"O24-induction of human keratinocytes into enamel -secreting ameloblasts","volume":"49","author":"Wang","year":"2011","journal-title":"Bull. Groupement Int. Rech. Sci. Stomatol. Odontol."},{"key":"10.1016\/j.biomaterials.2019.119591_bib69","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.1111\/j.1523-1747.2003.12616.x","article-title":"Crucial effects of fibroblasts and keratinocyte growth factor on morphogenesis of reconstituted human oral epithelium","volume":"121","author":"Costea","year":"2003","journal-title":"J. Investig. Dermatol."},{"key":"10.1016\/j.biomaterials.2019.119591_bib70","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1902\/cap.2015.140052","article-title":"Emerging regenerative approaches for periodontal reconstruction: practical applications from the AAP regeneration workshop","volume":"5","author":"Rios","year":"2015","journal-title":"Clin. Adv. Periodontics"},{"key":"10.1016\/j.biomaterials.2019.119591_bib71","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/S8756-3282(02)00798-6","article-title":"Improvement of fracture healing by systemic administration of growth hormone and local application of insulin-like growth factor-1 and transforming growth factor-beta 1","volume":"31","author":"Schmidmaier","year":"2002","journal-title":"Bone"},{"key":"10.1016\/j.biomaterials.2019.119591_bib72","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/S8756-3282(00)00456-7","article-title":"Local application of growth factors (insulin-like growth factor-1 and transforming growth factor-beta 1) from a biodegradable poly(D,L-lactide) coating of osteosynthetic implants accelerates fracture healing in rats","volume":"28","author":"Schmidmaier","year":"2001","journal-title":"Bone"},{"key":"10.1016\/j.biomaterials.2019.119591_bib73","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1615\/JLongTermEffMedImplants.v16.i1.70","article-title":"Collective review: bioactive implants coated with poly(D,L-lactide) and growth factors IGF-I, TGF-beta1, or BMP-2 for stimulation of fracture healing","volume":"16","author":"Schmidmaier","year":"2006","journal-title":"J. Long Term Eff. Med. Implant."},{"key":"10.1016\/j.biomaterials.2019.119591_bib74","doi-asserted-by":"crossref","DOI":"10.1186\/1749-799X-2-27","article-title":"Proliferating and differentiating effects of three different growth factors on pluripotent mesenchymal cells and osteoblast like cells","volume":"2","author":"Wildemann","year":"2007","journal-title":"J. Orthop. Surg. Res."},{"key":"10.1016\/j.biomaterials.2019.119591_bib75","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1007\/s00402-015-2253-3","article-title":"Reaming in treatment of non-unions in long bones: cytokine expression course as a tool for evaluation of non-union therapy","volume":"135","author":"Westhauser","year":"2015","journal-title":"Arch. Orthop. Trauma Surg."},{"key":"10.1016\/j.biomaterials.2019.119591_bib76","first-page":"342","article-title":"Quantification of TGF-beta 1, PDGF and IGF-1 cytokine expression after fracture treatment vs. non-union therapy via masquelet","volume":"47","author":"Fischer","year":"2016","journal-title":"Inj. Int. J. Care Inj."},{"key":"10.1016\/j.biomaterials.2019.119591_bib77","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.ghir.2007.09.002","article-title":"Systemic response of the GH\/IGF-I axis in timely versus delayed fracture healing","volume":"18","author":"Weiss","year":"2008","journal-title":"Growth Hormone IGF Res."},{"key":"10.1016\/j.biomaterials.2019.119591_bib78","article-title":"Periodontal soft tissue root coverage procedures: practical applications from the AAP regeneration workshop (vol 5, pg 2, 2015)","volume":"5","author":"Richardson","year":"2015","journal-title":"Clin. Adv. Periodontics"},{"key":"10.1016\/j.biomaterials.2019.119591_bib79","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.1038\/81161","article-title":"Removal of antibiotic resistance genes from transgenic tobacco plastids","volume":"18","author":"Iamtham","year":"2000","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.biomaterials.2019.119591_bib80","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1186\/s13059-016-1004-2","article-title":"Chloroplast genomes: diversity, evolution, and applications in genetic engineering","volume":"17","author":"Daniell","year":"2016","journal-title":"Genome Biol."},{"key":"10.1016\/j.biomaterials.2019.119591_bib81","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1038\/nprot.2007.522","article-title":"A protocol for expression of foreign genes in chloroplasts","volume":"3","author":"Verma","year":"2008","journal-title":"Nat. Protoc."},{"key":"10.1016\/j.biomaterials.2019.119591_bib82","doi-asserted-by":"crossref","first-page":"2088","DOI":"10.1104\/pp.109.152017","article-title":"The role of heterologous chloroplast sequence elements in transgene integration and expression","volume":"152","author":"Ruhlman","year":"2010","journal-title":"Plant Physiol."},{"key":"10.1016\/j.biomaterials.2019.119591_bib83","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.bone.2012.12.006","article-title":"Chemokine expression is upregulated in chondrocytes in diabetic fracture healing","volume":"53","author":"Alblowi","year":"2013","journal-title":"Bone"},{"key":"10.1016\/j.biomaterials.2019.119591_bib84","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1359\/jbmr.070115","article-title":"Diminished bone formation during diabetic fracture healing is related to the premature resorption of cartilage associated with increased osteoclast activity","volume":"22","author":"Kayal","year":"2007","journal-title":"J. Bone Miner. Res."},{"key":"10.1016\/j.biomaterials.2019.119591_bib85","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.bone.2017.02.014","article-title":"TNFalpha contributes to diabetes impaired angiogenesis in fracture healing","volume":"99","author":"Lim","year":"2017","journal-title":"Bone"}],"container-title":["Biomaterials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0142961219306908?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0142961219306908?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T16:48:36Z","timestamp":1758905316000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0142961219306908"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3]]},"references-count":85,"alternative-id":["S0142961219306908"],"URL":"https:\/\/doi.org\/10.1016\/j.biomaterials.2019.119591","relation":{},"ISSN":["0142-9612"],"issn-type":[{"value":"0142-9612","type":"print"}],"subject":[],"published":{"date-parts":[[2020,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Oral delivery of novel human IGF-1 bioencapsulated in lettuce cells promotes musculoskeletal cell proliferation, differentiation and diabetic fracture healing","name":"articletitle","label":"Article Title"},{"value":"Biomaterials","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.biomaterials.2019.119591","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2019 The Authors. Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}],"article-number":"119591"}}