Local Spinal Cord Injury Treatment Using a Dental Pulp Stem Cell Encapsulated H2S Releasing Multifunctional Injectable Hydrogel

Author:

Albashari Abdullkhaleg Ali12,He Yan34ORCID,Luo Yu1,Duan Xingxiang1,Ali Jihea5,Li Mingchang6,Fu Dehao7,Xiang Yangfan2,Peng Youjian1,Li Song2,Luo Lihua2,Zan Xingjie8,Kumeria Tushar91011ORCID,Ye Qingsong124ORCID

Affiliation:

1. Center of Regenerative Medicine, Department of Stomatology Renmin Hospital of Wuhan University Wuhan Hubei 430060 China

2. School and Hospital of Stomatology Wenzhou Medical University Wenzhou Zhejiang 325035 China

3. Laboratory for Regenerative Medicine Tianyou Hospital Wuhan University of Science and Technology Wuhan Hubei 430064 China

4. Oral Maxillofacial Department Massachusetts General Hospital Harvard Medical School Boston MA 02114 USA

5. College of Life and Environmental Science Wenzhou University Wenzhou Zhejiang 325035 China

6. Department of Neurosurgery Renmin Hospital of Wuhan University Wuhan Hubei 430060 China

7. Department of Orthopaedics Shanghai Sixth People's Hospital Shanghai Jiao Tong University Shanghai 200233 China

8. Wenzhou Institute University of China Academy of Science Wenzhou Zhejiang 325024 China

9. School of Materials Science and Engineering University of New South Wales Sydney New South Wales 2052 Australia

10. Australian Center for NanoMedicine University of New South Wales Sydney New South Wales 2052 Australia

11. School of Pharmacy University of Queensland Brisbane Queensland 4102 Australia

Abstract

AbstractSpinal cord injury (SCI) commonly induces nerve damage and nerve cell degeneration. In this work, a novel dental pulp stem cells (DPSCs) encapsulated thermoresponsive injectable hydrogel with sustained hydrogen sulfide (H2S) delivery is demonstrated for SCI repair. For controlled and sustained H2S gas therapy, a clinically tested H2S donor (JK) loaded octysilane functionalized mesoporous silica nanoparticles (OMSNs) are incorporated into the thermosensitive hydrogel made from Pluronic F127 (PF‐127). The JK‐loaded functionalized MSNs (OMSF@JK) promote preferential M2‐like polarization of macrophages and neuronal differentiation of DPSCs in vitro. OMSF@JK incorporated PF‐127 injectable hydrogel (PF‐OMSF@JK) has a soft consistency similar to that of the human spinal cord and thus, shows a high cytocompatibility with DPSCs. The cross‐sectional micromorphology of the hydrogel shows a continuous porous structure. Last, the PF‐OMSF@JK composite hydrogel considerably improves the in vivo SCI regeneration in Sprague–Dawley rats through a reduction in inflammation and neuronal differentiation of the incorporated stem cells as confirmed using western blotting and immunohistochemistry. The highly encouraging in vivo results prove that this novel design on hydrogel is a promising therapy for SCI regeneration with the potential for clinical translation.

Funder

National Health and Medical Research Council

Natural Science Foundation of Zhejiang Province

National Natural Science Foundation of China

Publisher

Wiley

Subject

Pharmaceutical Science,Biomedical Engineering,Biomaterials

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