title: Injectable microcryogels reinforced alginate encapsulation of mesenchymal stromal cells for leak-proof delivery and alleviation of canine disc degeneration.
abstract: In situ crosslinked thermo-responsive hydrogel applied for minimally invasive treatment of intervertebral disc degeneration (IVDD) may not prevent extrusion of cell suspension from injection site due to high internal pressure of intervertebral disc (IVD), causing treatment failure or osteophyte formation. In this study, mesenchymal stromal cells (MSCs) were encapsulated in alginate precursor and loaded into previously developed macroporous PGEDA-derived microcryogels (PMs) to form three-dimensional (3D) microscale cellular niches, enabling non-thermo-responsive alginate hydrogel to be injectable. The PMs reinforced alginate hydrogel showed superior elasticity compared to alginate hydrogel alone and could well protect encapsulated cells through injection. Chondrogenic committed MSCs in the injectable microniches expressed higher level of nucleus pulposus (NP) cell markers compared to 2D cultured cells. In an ex vivo organ culture model, injection of MSCs-laden PMs into NP tissue prevented cell leakage, improved cell retention and survival compared to free cell injection. In canine IVDD models, alleviated degeneration was observed in MSCs-laden PMs treated group after six months which was superior to other treated groups. Our results provide in-depth demonstration of injectable alginate hydrogel reinforced by PMs as a leak-proof cell delivery system for augmented regenerative therapy of IVDD in canine models.
authors.affiliation: Department of Biomedical Engineering, School of Medicine, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Tsinghua University, Beijing 100084, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zeng
authors.affiliation: Department of Orthopaedics, Navy General Hospital, Beijing 100048, China; Department of Orthopedic Surgery, First Affiliated Hospital, Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Chun
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Biomedical Engineering, School of Medicine, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Tsinghua University, Beijing 100084, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China.
authors.forename: Qinyouen
authors.initials: Q
authors.lastname: Fu
authors.affiliation: Department of Orthopaedics, Navy General Hospital, Beijing 100048, China.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Han
authors.affiliation: Department of Biomedical Engineering, School of Medicine, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Tsinghua University, Beijing 100084, China.
authors.forename: Yaqian
authors.initials: Y
authors.lastname: Li
authors.affiliation: School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China.
authors.forename: Siyu
authors.initials: S
authors.lastname: Feng
authors.affiliation: Department of Biomedical Engineering, School of Medicine, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Tsinghua University, Beijing 100084, China.
authors.forename: Xiaokang
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Biomedical Engineering, School of Medicine, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Tsinghua University, Beijing 100084, China.
authors.forename: Chunxiao
authors.initials: C
authors.lastname: Qi
authors.affiliation: Department of Orthopaedics, Navy General Hospital, Beijing 100048, China.
authors.forename: Jianhong
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Orthopaedics, Navy General Hospital, Beijing 100048, China.
authors.forename: Deli
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Biomedical Engineering, The Johns Hopkins University, Baltimore, MD 21231, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Corbett
authors.affiliation: Tissue Engineering Laboratory, Department of Mechanical Engineering, The University of Hong Kong, Pokfulam Rd, Hong Kong Special Administrative Region, China.
authors.forename: Barbara P
authors.initials: BP
authors.lastname: Chan
authors.affiliation: Department of Orthopaedics, Navy General Hospital, Beijing 100048, China. Electronic address: ruandikengh@163.com.
authors.forename: Dike
authors.initials: D
authors.lastname: Ruan
authors.affiliation: Department of Biomedical Engineering, School of Medicine, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Tsinghua University, Beijing 100084, China. Electronic address: duyanan@tsinghua.edu.cn.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Du
mesh_terms: D000464:Alginates / Q000737:chemistry*; D000818:Animals; D059985:Cryogels; D004285:Dogs; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D055959:Intervertebral Disc Degeneration / Q000628:therapy*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*
chemical_list: D000464:Alginates; D059985:Cryogels; D006603:Hexuronic Acids; D020723:Glucuronic Acid
keywords: Alginate; Canine intervertebral disc degeneration; Leak-proof; Mesenchymal stromal cell; Microcryogel