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Systemic therapeutic investigation of transplanting nucleus pulposus-derived mesenchymal stem cells embedded on Gefitinib-chitosan/collagen blended injectable hydrogels to the intervertebral disc regeneration treatment using a rat model

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Abstract

The stem cell-based therapeutic approaches for intervertebral disc regeneration are thought to have promising attention in the treatment of degenerative disc disease, which is closely related to lower back pain. In this study, we developed a Gefitinib small molecules-crosslinked blended chitosan/collagen type 1 biopolymeric hydrogel (Ge-CS/COL-I) that can be injected and exhibit better in-situ processability than bare hydrogels, while conserving the ability to direct differentiation of nucleus pulposus-derived mesenchymal stem cells (NPMSCs). The blended injectable hydrogel was explored as a cell carrier and scaffold for nucleus pulposus (NP) tissue engineering because of its biocompatibility, adaptable qualities, and microporous architecture. The prepared hydrogel system might be delivered effectively using a minimally invasive method, and its mechanical properties could be tailored to match the rigidity of the native human nucleus pulposus, according to oscillatory rheology ability. The most of the cellular components were eliminated, although the extracellular matrix and microstructure were substantially retained, according to histopathological and DAPI staining observations using fluorescence microscopic method. The ability of NPMSCs-loaded hydrogel to regenerate degenerated NP in a rat model was investigated in vivo. The findings indicate that NPMSC could cause differentiation in blended hydrogel in vivo and were greatly biocompatible. At eight weeks following injection, the disc height index and MRI index of NPMSCs-loaded hydrogel groups have both been noticeably higher than those of the other control groups. After eight weeks, immunofluorescence and histological staining revealed that the NPMSCs-loaded hydrogel had also partially repaired the structure and ECM content of the degraded NP. Combined, our results demonstrate that a hydrogel system has a great deal of potential for NPMSC administration for promoting IVD regeneration in the rat model.

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Acknowledgements

This study was supported by Key Natural Science Research Project of Anhui Provincial Department of Education (No. KJ2021A0802), PR China.

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Authors and Affiliations

  1. Department of Orthopedics, The First Affiliated Hospital of Bengbu Medical College, No. 287, Changhuai Road, Bengbu, 233004, China

    Gang Xu, Kun Zhu, Yuchen Ye, Pinghui Zhou, Zhengqi Bao & Changchun Zhang

  2. Key Laboratory of Tissue Transplantation of Anhui Province, Bengbu, 233004, China

    Gang Xu

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  1. Gang Xu
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Contributions

GX and KZ–Conception and experimental design; YY and PZ–Experimental analyses and carrying out measurements; ZB–Formal analysis and results interpretations; CZ*–Supervision and manuscript composition.

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Correspondence to Changchun Zhang.

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The US National Institutes of Health's Laboratory Animals published protocol followed to conduct experiments of animal care and use. The laboratory Animal Management and Ethics Committee of Bengbu Medical College (Ethical number:2022-0294) provided consent approval to all animal experiments.

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Xu, G., Zhu, K., Ye, Y. et al. Systemic therapeutic investigation of transplanting nucleus pulposus-derived mesenchymal stem cells embedded on Gefitinib-chitosan/collagen blended injectable hydrogels to the intervertebral disc regeneration treatment using a rat model. J Mater Sci 58, 14480–14499 (2023). https://doi.org/10.1007/s10853-023-08918-1

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