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Proper animal experimental designs for preclinical research of biomaterials for intervertebral disc regeneration

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单位: [1]Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China. [2]Division of Cardiology,Department of Internal Medicine,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei Province,China. [3]Hubei Key Laboratory of Genetics and Molecular Mechanism of Cardiologic Disorders, Huazhong University of Science and Technology, Wuhan, Hubei Province, China. [4]Department of Orthopaedic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China. [5]Department of Orthopaedic Surgery, Institute for Cell Engineering, Johns Hopkins University, Baltimore, MD, USA.
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关键词: animal model biomaterials intervertebral disc preclinical evaluation translational medicine

摘要:
Low back pain is a vital musculoskeletal disease that impairs life quality, leads to disability and imposes heavy economic burden on the society, while it is greatly attributed to intervertebral disc degeneration (IDD). However, the existing treatments, such as medicines, chiropractic adjustments and surgery, cannot achieve ideal disc regeneration. Therefore, advanced bioactive therapies are implemented, including stem cells delivery, bioreagents administration, and implantation of biomaterials etc. Among these researches, few reported unsatisfying regenerative outcomes. However, these advanced therapies have barely achieved successful clinical translation. The main reason for the inconsistency between satisfying preclinical results and poor clinical translation may largely rely on the animal models that cannot actually simulate the human disc degeneration. The inappropriate animal model also leads to difficulties in comparing the efficacies among biomaterials in different reaches. Therefore, animal models that better simulate the clinical charateristics of human IDD should be acknowledged. In addition, in vivo regenerative outcomes should be carefully evaluated to obtain robust results. Nevertheless, many researches neglect certain critical characteristics, such as adhesive properties for biomaterials blocking annulus fibrosus defects and hyperalgesia that is closely related to the clinical manifestations, e.g., low back pain. Herein, in this review, we summarized the animal models established for IDD, and highlighted the proper models and parameters that may result in acknowledged IDD models. Then, we discussed the existing biomaterials for disc regeneration and the characteristics that should be considered for regenerating different parts of discs. Finally, well-established assays and parameters for in vivo disc regeneration are explored.

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第一作者单位: [1]Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
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