{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T07:41:13Z","timestamp":1789544473504,"version":"build-2803163510"},"reference-count":55,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,2,3]],"date-time":"2023-02-03T00:00:00Z","timestamp":1675382400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006245","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["109-2314-B-182-074"],"award-info":[{"award-number":["109-2314-B-182-074"]}],"id":[{"id":"10.13039\/501100006245","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006245","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["109-2314-B-182A-056-MY3"],"award-info":[{"award-number":["109-2314-B-182A-056-MY3"]}],"id":[{"id":"10.13039\/501100006245","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006245","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["110-2314-B-182A-137-MY3"],"award-info":[{"award-number":["110-2314-B-182A-137-MY3"]}],"id":[{"id":"10.13039\/501100006245","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006245","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["CMRPG1L0041"],"award-info":[{"award-number":["CMRPG1L0041"]}],"id":[{"id":"10.13039\/501100006245","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006245","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["CMRPG3M0281"],"award-info":[{"award-number":["CMRPG3M0281"]}],"id":[{"id":"10.13039\/501100006245","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006245","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["CMRPG3M0282"],"award-info":[{"award-number":["CMRPG3M0282"]}],"id":[{"id":"10.13039\/501100006245","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004606","name":"Chang Gung Medical Foundation, Chang Gung Memorial Hospital, Taiwan","doi-asserted-by":"publisher","award":["109-2314-B-182-074"],"award-info":[{"award-number":["109-2314-B-182-074"]}],"id":[{"id":"10.13039\/501100004606","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004606","name":"Chang Gung Medical Foundation, Chang Gung Memorial Hospital, Taiwan","doi-asserted-by":"publisher","award":["109-2314-B-182A-056-MY3"],"award-info":[{"award-number":["109-2314-B-182A-056-MY3"]}],"id":[{"id":"10.13039\/501100004606","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004606","name":"Chang Gung Medical Foundation, Chang Gung Memorial Hospital, Taiwan","doi-asserted-by":"publisher","award":["110-2314-B-182A-137-MY3"],"award-info":[{"award-number":["110-2314-B-182A-137-MY3"]}],"id":[{"id":"10.13039\/501100004606","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004606","name":"Chang Gung Medical Foundation, Chang Gung Memorial Hospital, Taiwan","doi-asserted-by":"publisher","award":["CMRPG1L0041"],"award-info":[{"award-number":["CMRPG1L0041"]}],"id":[{"id":"10.13039\/501100004606","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004606","name":"Chang Gung Medical Foundation, Chang Gung Memorial Hospital, Taiwan","doi-asserted-by":"publisher","award":["CMRPG3M0281"],"award-info":[{"award-number":["CMRPG3M0281"]}],"id":[{"id":"10.13039\/501100004606","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004606","name":"Chang Gung Medical Foundation, Chang Gung Memorial Hospital, Taiwan","doi-asserted-by":"publisher","award":["CMRPG3M0282"],"award-info":[{"award-number":["CMRPG3M0282"]}],"id":[{"id":"10.13039\/501100004606","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Vascularized composite allotransplantation is an emerging strategy for the reconstruction of unique defects such as amputated limbs that cannot be repaired with autologous tissues. In order to ensure the function of transplanted limbs, the functional recovery of the anastomosed peripheral nerves must be confirmed. The immunosuppressive drug, tacrolimus, has been reported to promote nerve recovery in animal models. However, its repeated dosing comes with risks of systemic malignancies and opportunistic infections. Therefore, drug delivery approaches for locally sustained release can be designed to overcome this issue and reduce systemic complications. We developed a mixed thermosensitive hydrogel (poloxamer (PLX)-poly(l-alanine-lysine with Pluronic F-127) for the time-dependent sustained release of tacrolimus in our previous study. In this study, we demonstrated that the hydrogel drug degraded in a sustained manner and locally released tacrolimus in mice over one month without affecting the systemic immunity. The hydrogel drug significantly improved the functional recovery of injured sciatic nerves as assessed using five-toe spread and video gait analysis. Neuroregeneration was validated in hydrogel\u2013drug-treated mice using axonal analysis. The hydrogel drug did not cause adverse effects in the mouse model during long-term follow-up. The local injection of encapsulated-tacrolimus mixed thermosensitive hydrogel accelerated peripheral nerve recovery without systemic adverse effects.<\/jats:p>","DOI":"10.3390\/pharmaceutics15020508","type":"journal-article","created":{"date-parts":[[2023,2,3]],"date-time":"2023-02-03T03:04:23Z","timestamp":1675393463000},"page":"508","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Sustained Release of Tacrolimus Embedded in a Mixed Thermosensitive Hydrogel for Improving Functional Recovery of Injured Peripheral Nerves in Extremities"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6272-6948","authenticated-orcid":false,"given":"Aline Yen Ling","family":"Wang","sequence":"first","affiliation":[{"name":"Center for Vascularized Composite Allotransplantation, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuan-Hung","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Physical Medicine & Rehabilitation, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan"},{"name":"College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7025-0553","authenticated-orcid":false,"given":"Hsiu-Chao","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, National Tsing Hua University, Hsinchu 30013, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles Yuen Yung","family":"Loh","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery, Addenbrooke\u2019s Hospital, Hills Road, Cambridge CB2 0SP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4998-3338","authenticated-orcid":false,"given":"Yun-Ching","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Health Industry Technology Management, Chung Shan Medical University, Taichung 40201, Taiwan"},{"name":"Department of Medical Research, Chung Shan Medical University Hospital, Taichung 40201, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6443-0200","authenticated-orcid":false,"given":"Ana Elena","family":"Avi\u00f1a","sequence":"additional","affiliation":[{"name":"Center for Vascularized Composite Allotransplantation, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan"},{"name":"International Ph.D. Program in Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chin-Ming","family":"Lee","sequence":"additional","affiliation":[{"name":"Center for Vascularized Composite Allotransplantation, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7456-8681","authenticated-orcid":false,"given":"I-Ming","family":"Chu","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, National Tsing Hua University, Hsinchu 30013, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fu-Chan","family":"Wei","sequence":"additional","affiliation":[{"name":"Center for Vascularized Composite Allotransplantation, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan"},{"name":"College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan"},{"name":"Department of Plastic Surgery, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1111\/j.1432-2277.2012.01433.x","article-title":"Outcomes with respect to disabilities of the upper limb after hand allograft transplantation: A systematic review","volume":"25","author":"Landin","year":"2012","journal-title":"Transpl. Int."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.jht.2013.10.007","article-title":"Upper extremity limb loss: Functional restoration from prosthesis and targeted reinnervation to transplantation","volume":"27","author":"Carlsen","year":"2014","journal-title":"J. Hand Ther."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/j.hcl.2011.07.002","article-title":"Clinical strategies to enhance nerve regeneration in composite tissue allotransplantation","volume":"27","author":"Glaus","year":"2011","journal-title":"Hand Clin."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/0006-8993(74)90002-X","article-title":"Calcium-induced degeneration of axoplasm in isolated segments of rat peripheral nerve","volume":"69","author":"Schlaepfer","year":"1974","journal-title":"Brain Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1002\/1098-2752(2000)20:8<360::AID-MICR4>3.0.CO;2-E","article-title":"Hand transplantation: Comparisons and observations of the first four clinical cases","volume":"20","author":"Francois","year":"2000","journal-title":"Microsurgery"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/BF02740621","article-title":"The cellular and molecular basis of peripheral nerve regeneration","volume":"14","author":"Fu","year":"1997","journal-title":"Mol. Neurobiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1002\/mus.880150610","article-title":"Wallerian degeneration in human nerves: Serial electrophysiological studies","volume":"15","author":"Chaudhry","year":"1992","journal-title":"Muscle Nerve"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1111\/j.1460-9568.1996.tb01237.x","article-title":"Interleukin 6 in intact and injured mouse peripheral nerves","volume":"8","author":"Reichert","year":"1996","journal-title":"Eur. J. Neurosci."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Loh, C.Y., Wang, A.Y., Kao, H.K., Cardona, E., Chuang, S.H., and Wei, F.C. (2016). Episomal Induced Pluripotent Stem Cells Promote Functional Recovery of Transected Murine Peripheral Nerve. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0164696"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"112S","DOI":"10.1177\/0963689719886534","article-title":"Episomal Induced Pluripotent Stem Cells: Functional and Potential Therapeutic Applications","volume":"28","author":"Wang","year":"2019","journal-title":"Cell Transplant."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1560","DOI":"10.1177\/0963689719880543","article-title":"Topical Application of Human Wharton\u2019s Jelly Mesenchymal Stem Cells Accelerates Mouse Sciatic Nerve Recovery and is Associated with Upregulated Neurotrophic Factor Expression","volume":"28","author":"Wang","year":"2019","journal-title":"Cell Transplant."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Wang, A.Y.L., Loh, C.Y.Y., Shen, H.H., Hsieh, S.Y., Wang, I.K., Lee, C.M., and Lin, C.H. (2020). Human Wharton\u2019s Jelly Mesenchymal Stem Cell-Mediated Sciatic Nerve Recovery Is Associated with the Upregulation of Regulatory T Cells. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21176310"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1126\/science.1702904","article-title":"Chemistry and biology of the immunophilins and their immunosuppressive ligands","volume":"251","author":"Schreiber","year":"1991","journal-title":"Science"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1016\/0092-8674(91)90124-H","article-title":"Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes","volume":"66","author":"Liu","year":"1991","journal-title":"Cell"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"924","DOI":"10.3171\/jns.2002.96.5.0924","article-title":"Axonal regeneration after cold preservation of nerve allografts and immunosuppression with tacrolimus in mice","volume":"96","author":"Grand","year":"2002","journal-title":"J. Neurosurg."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1002\/mus.10195","article-title":"Bimodal dose-dependence of FK506 on the rate of axonal regeneration in mouse peripheral nerve","volume":"26","author":"Udina","year":"2002","journal-title":"Muscle Nerve"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1832","DOI":"10.1097\/01.PRS.0000091167.27303.18","article-title":"Dose-dependent effects of FK506 on neuroregeneration in a rat model","volume":"112","author":"Yang","year":"2003","journal-title":"Plast. Reconstr. Surg."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1055\/s-0032-1333316","article-title":"FK506 and nerve regeneration: Past, present, and future","volume":"29","author":"Konofaos","year":"2013","journal-title":"J. Reconstr. Microsurg."},{"key":"ref_19","first-page":"1202","article-title":"Immunophilin FK506-binding protein 52 (not FK506-binding protein 12) mediates the neurotrophic action of FK506","volume":"289","author":"Gold","year":"1999","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1006\/exnr.1997.6630","article-title":"A nonimmunosuppressant FKBP-12 ligand increases nerve regeneration","volume":"147","author":"Gold","year":"1997","journal-title":"Exp. Neurol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1002\/mus.1088","article-title":"Effects of FK506 on nerve regeneration and reinnervation after graft or tube repair of long nerve gaps","volume":"24","author":"Navarro","year":"2001","journal-title":"Muscle Nerve"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1007\/s00109-012-0925-9","article-title":"Early steps of microglial activation are directly affected by neuroprotectant FK506 in both in vitro inflammation and in rat model of stroke","volume":"90","author":"Zawadzka","year":"2012","journal-title":"J. Mol. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/S0014-4886(03)00173-0","article-title":"FK506 enhances reinnervation by regeneration and by collateral sprouting of peripheral nerve fibers","volume":"183","author":"Udina","year":"2003","journal-title":"Exp. Neurol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1046\/j.1529-8027.2003.03020.x","article-title":"Comparative dose-dependence study of FK506 on transected mouse sciatic nerve repaired by allograft or xenograft","volume":"8","author":"Udina","year":"2003","journal-title":"J. Peripher. Nerv. Syst."},{"key":"ref_25","first-page":"287","article-title":"The immunosuppressant FK506 increases functional recovery and nerve regeneration following peripheral nerve injury","volume":"6","author":"Gold","year":"1994","journal-title":"Restor. Neurol. Neurosci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1002\/mus.20029","article-title":"Comparison of continuous and discontinuous FK506 administration on autograft or allograft repair of sciatic nerve resection","volume":"29","author":"Udina","year":"2004","journal-title":"Muscle Nerve"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1007\/BF02740664","article-title":"FK506 and the role of immunophilins in nerve regeneration","volume":"15","author":"Gold","year":"1997","journal-title":"Mol. Neurobiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1002\/glia.20025","article-title":"FK506 enhances regeneration of axons across long peripheral nerve gaps repaired with collagen guides seeded with allogeneic Schwann cells","volume":"47","author":"Udina","year":"2004","journal-title":"Glia"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1006\/exnr.2002.7878","article-title":"FK506 increases peripheral nerve regeneration after chronic axotomy but not after chronic schwann cell denervation","volume":"175","author":"Sulaiman","year":"2002","journal-title":"Exp. Neurol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1002\/jnr.20447","article-title":"Non-FK506-binding protein-12 neuroimmunophilin ligands increase neurite elongation and accelerate nerve regeneration","volume":"80","author":"Gold","year":"2005","journal-title":"J. Neurosci. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1097\/00001756-199802160-00031","article-title":"Oral administration of a nonimmunosuppressant FKBP-12 ligand speeds nerve regeneration","volume":"9","author":"Gold","year":"1998","journal-title":"Neuroreport"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1007\/s12664-014-0456-0","article-title":"Tacrolimus-related adverse effects in liver transplant recipients: Its association with trough concentrations","volume":"33","author":"Varghese","year":"2014","journal-title":"Indian J. Gastroenterol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1097\/ICO.0000000000000258","article-title":"Efficacy and safety of systemic tacrolimus in high-risk penetrating keratoplasty after graft failure with systemic cyclosporine","volume":"33","author":"Yamazoe","year":"2014","journal-title":"Cornea"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1111\/aor.13551","article-title":"Tacrolimus: 20 years of use in adult kidney transplantation. What we should know about its nephrotoxicity","volume":"44","author":"Bentata","year":"2020","journal-title":"Artif. Organs"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"735","DOI":"10.3109\/0886022X.2013.780621","article-title":"Tacrolimus-induced severe cholestasis complicating renal transplantation","volume":"35","author":"Yadav","year":"2013","journal-title":"Ren. Fail."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1517\/17425255.2014.964205","article-title":"Tacrolimus in pancreas transplant: A focus on toxicity, diabetogenic effect and drug-drug interactions","volume":"10","author":"Rangel","year":"2014","journal-title":"Expert Opin Drug Metab. Toxicol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"690","DOI":"10.2215\/CJN.07320810","article-title":"Tacrolimus-induced neutropenia in renal transplant recipients","volume":"6","author":"Dierickx","year":"2011","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1993","DOI":"10.1016\/j.polymer.2008.01.027","article-title":"Hydrogels in drug delivery: Progress and challenges","volume":"49","author":"Hoare","year":"2008","journal-title":"Polymer"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4337","DOI":"10.1016\/S0142-9612(03)00340-5","article-title":"Hydrogels for tissue engineering: Scaffold design variables and applications","volume":"24","author":"Drury","year":"2003","journal-title":"Biomaterials"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"5185","DOI":"10.1016\/j.biomaterials.2007.07.044","article-title":"Hydrogel biomaterials: A smart future?","volume":"28","author":"Kopecek","year":"2007","journal-title":"Biomaterials"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Lin, H.C., Anggelia, M.R., Cheng, C.C., Ku, K.L., Cheng, H.Y., Wen, C.J., Wang, A.Y.L., Lin, C.H., and Chu, I.M. (2019). A Mixed Thermosensitive Hydrogel System for Sustained Delivery of Tacrolimus for Immunosuppressive Therapy. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11080413"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.ijpharm.2011.01.037","article-title":"Development and characterisation of modified poloxamer 407 thermoresponsive depot systems containing cubosomes","volume":"408","author":"Kojarunchitt","year":"2011","journal-title":"Int. J. Pharm."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"39828","DOI":"10.1038\/srep39828","article-title":"Experimental immunological demyelination enhances regeneration in autograft-repaired long peripheral nerve gaps","volume":"6","author":"Ge","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1242\/dev.072371","article-title":"Vimentin regulates peripheral nerve myelination","volume":"139","author":"Triolo","year":"2012","journal-title":"Development"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Chomiak, T., and Hu, B. (2009). What is the optimal value of the g-ratio for myelinated fibers in the rat CNS? A theoretical approach. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0007754"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"7665","DOI":"10.1523\/JNEUROSCI.0444-06.2006","article-title":"Beta1-integrin signaling mediates premyelinating oligodendrocyte survival but is not required for CNS myelination and remyelination","volume":"26","author":"Benninger","year":"2006","journal-title":"J. Neurosci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.neuroimage.2016.09.018","article-title":"g-Ratio weighted imaging of the human spinal cord in vivo","volume":"145","author":"Duval","year":"2017","journal-title":"Neuroimage"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.neuroimage.2017.08.038","article-title":"Promise and pitfalls of g-ratio estimation with MRI","volume":"182","author":"Campbell","year":"2018","journal-title":"Neuroimage"},{"key":"ref_49","first-page":"1084","article-title":"Comparative dose-dependence study of FK506 and cyclosporin A on the rate of axonal regeneration in the rat sciatic nerve","volume":"282","author":"Wang","year":"1997","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1111\/j.1432-2277.1997.tb00530.x","article-title":"Rescue therapy with tacrolimus (FK 506) in renal transplant recipients--a Scandinavian multicenter analysis","volume":"10","author":"Felldin","year":"1997","journal-title":"Transpl. Int."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"7509","DOI":"10.1523\/JNEUROSCI.15-11-07509.1995","article-title":"The immunosuppressant FK506 increases the rate of axonal regeneration in rat sciatic nerve","volume":"15","author":"Gold","year":"1995","journal-title":"J. Neurosci."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"De Paz, D., Avina, A.E., Cardona, E., Lee, C.M., Lin, C.H., Lin, C.H., Wei, F.C., and Wang, A.Y.L. (2021). The Mandible Ameliorates Facial Allograft Rejection and Is Associated with the Development of Regulatory T Cells and Mixed Chimerism. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222011104"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1097\/PRS.0000000000005774","article-title":"A New Face Subunit Transplant Model in Mice, Containing Skin, Mandible, and Oral Mucosa for Future Face Vascularized Composite Allotransplantation Studies","volume":"144","author":"Cardona","year":"2019","journal-title":"Plast. Reconstr. Surg."},{"key":"ref_54","first-page":"1","article-title":"Reviewing immunosuppressive regimens in animal models for vascularized composite allotransplantation","volume":"5","year":"2018","journal-title":"Plast. Aesthet. Res."},{"key":"ref_55","unstructured":"Chu, I.M., Lin, H.-C., Cheng, C.C., and Ku, K.L. (2019). Drug Carrier and Drug Delivery System Using the Same. (I649096), Patent."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/15\/2\/508\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:23:06Z","timestamp":1760120586000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/15\/2\/508"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,3]]},"references-count":55,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["pharmaceutics15020508"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics15020508","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,3]]}}}