title: Adhesive barrier/directional controlled release for cartilage repair by endogenous progenitor cell recruitment.
abstract: A new design concept in controlled release chemistry is reported in this study. Unlike current depots that release drugs in all direction by an isotropic way, we demonstrate that directional release only to a clinically beneficial direction results in improved disease treatment. To achieve the directional drug release, catecholamine adhesion chemistry was used to establish robust interfacial adhesion. For this purpose, water-resistant catechol-conjugated chitosan (CHI-C) adhesive gel patch was used. We chose a cartilage repair model to test our hypothesis. The adhesive barrier exhibited directional release of platelet-derived growth factor-AA (PDGF-AA) only toward the marrow cavity defect areas. This directional PDGF-AA release greatly promoted effective recruitment of human mesenchymal stem cell (hMSCs). Moreover, the adhesive barrier prevented further migration and dispersion of the hMSCs that otherwise were not properly located to the disease site. In vivo imaging and macroscopic histological assessments demonstrated significant improvement of cartilage tissue, suggesting directional controlled release can be a general concept for improvement of tissue regeneration. This CHI-C barrier is expected to make a significant contribution in cartilage tissue engineering without cell transplantation as well as application for other tissue engineering.
authors.affiliation: College of Medicine, Dongguk University, Goyang, Republic of Korea; Department of Orthopaedics, Dongguk University Ilsan Hospital, Goyang, Republic of Korea.
authors.forename: Jong Min
authors.initials: JM
authors.lastname: Lee
authors.affiliation: Graduate School of Nanoscience and Technology, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Ryu
authors.affiliation: Department of Orthopaedics, Dongguk University Ilsan Hospital, Goyang, Republic of Korea.
authors.forename: Eun Ah
authors.initials: EA
authors.lastname: Kim
authors.affiliation: InnoTherapy, Daejeon, Republic of Korea.
authors.forename: Seongyeon
authors.initials: S
authors.lastname: Jo
authors.affiliation: School of Chemical and Biological Engineering, Seoul National University, Seoul, Korea.
authors.forename: Byung-Soo
authors.initials: BS
authors.lastname: Kim
authors.affiliation: Graduate School of Nanoscience and Technology, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea; Department of Chemistry, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea. Electronic address: haeshin@kaist.ac.kr.
authors.forename: Haeshin
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Orthopaedics, Dongguk University Ilsan Hospital, Goyang, Republic of Korea. Electronic address: gunil@duih.org.
authors.forename: Gun-Il
authors.initials: GI
authors.lastname: Im
mesh_terms: D000818:Animals; D002356:Cartilage / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
chemical_list: D010982:Platelet-Derived Growth Factor; C075278:platelet-derived growth factor A
keywords: Catechol-conjugated chitosan adhesive gel patch; Directional release; Human mesenchymal stem cells; In vivo imaging; Migration