A novel hydrogel-based treatment for complete transection spinal cord injury repair is driven by microglia/macrophages repopulation

Ma, Dezun; Zhao, Yannan; Huang, Lei; Xiao, Zhifeng; Chen, Bing; Shi, Yang; Shen, He; Dai, Jianwu

doi:10.1016/j.biomaterials.2020.119830

Cited by 84 publications

(86 citation statements)

References 75 publications

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“…Locomotor function of rats was evaluated by Basso, Beattie, and Bresnahan (BBB) scoring test (Basso et al, 1995) and inclined plane test (Dinh et al, 2009) on day 0, 7, 14, 21 and 28 after SCI surgery. In BBB scoring test, activity of hind limb of each animal was videotaped and recorded by three blinded observers.…”

Section: Locomotor Function Assessmentmentioning

confidence: 99%

“…Reports spanning various countries demonstrated that SCI has become a common disease affecting millions of individuals worldwide (Noonan et al, 2012;Smith et al, 2010Smith et al, -2015Saberi et al, 2016). Though great efforts have been made to seek effective treatment method for SCI (Ma et al, 2020;Zheng et al, 2020), no optimal therapeutic strategy has been achieved yet. Thus, continuing efforts of exploring effective and safe drug to treat SCI are needed.…”

Section: Introductionmentioning

confidence: 99%

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Irisin Protects Against Motor Dysfunction of Rats with Spinal Cord Injury via Adenosine 5'-Monophosphate (AMP)-Activated Protein Kinase-Nuclear Factor Kappa-B Pathway

et al. 2020

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The aim of the present research was to investigate the effects of irisin, a skeletal muscle-derived myokine, on spinal cord injury (SCI) in rats and explore the possible mechanisms. SCI model was constructed in male SD rats. The effects of irisin on SCI rats were assessed via behavior tests including Basso, Beattie, and Bresnahan (BBB) scoring method and inclined plane test, followed by histomorphology tests including HE staining, Nissl staining, and transmission electron microscope examination. Biochemical analyses including PCR, Western blots and ELISA were employed to further evaluate the changes at molecular level of SCI rats. In addition, lipopolysaccharide (LPS)-induced cell damage model was established in PC12 cells to verify the mechanism of irisin’s effect on nerve cells in vitro . Results showed that the BBB score and the angle of incline significantly decreased after SCI surgery, however, chronic irisin treatment improved SCI-induced motor dysfunction. HE and Nissl staining assays showed that SCI surgery induced histological injury of spinal cord, which could be reversed by irisin treatment. Morphological abnormality of nerve cells caused by SCI also could be alleviated by irisin. Further biochemical analyses showed that irisin inhibited SCI-induced overexpression of Interleukin-1β (IL-1β), Interleukin- 6 (IL-6), tumor necrosis factor alpha (TNF-α), inducible nitricoxidesynthase (iNOS) and Cyclooxygenase-2 (COX-2)], as well as nuclear factor kappa-B (NF-κB)p65 in rats, and the positive function of irisin could be reversed by Compound C treatment. In our in vitro study, LPS-induced declines of cell viability and neurite length of PC12 cell were inhibited by irisin treatment, and irisin inhibited LPS-induced overexpression of NF-κBp65, IL-1β, IL-6, TNF-α, iNOS and COX-2. These changes could be reversed by activated protein kinase (AMPK) siRNA pre-treatment. Taken together, irisin could protect the rats from SCI, and its protection is associated with the regulation of adenosine 5'-monophosphate-activated protein kinase (AMPK) - NF-κB signaling pathway.

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Section: Locomotor Function Assessmentmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Irisin Protects Against Motor Dysfunction of Rats with Spinal Cord Injury via Adenosine 5'-Monophosphate (AMP)-Activated Protein Kinase-Nuclear Factor Kappa-B Pathway

et al. 2020

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“…Owing to its excellent adhesive ability and biocompatibility, gelatin methacryloyl-dopamine (GelMA-DOPA) has been widely used in bone tissue engineering [31][32][33]. Liposomes, which are well-known for their excellent biocompatibility and satisfactory ability to control drug release, have been widely utilized in various types of drug delivery [34][35][36].…”

Section: Introductionmentioning

confidence: 99%

Sustained Release of Melatonin from GelMA Liposomes Reduced Osteoblast Apoptosis and Improved Implant Osseointegration in Osteoporosis

Xiao

Lin

Chen

et al. 2020

Oxidative Medicine and Cellular Longevity

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A reduction in bone mass around an implant is the main cause of implant loosening, especially in postmenopausal osteoporosis patients. In osteoporosis, excessive oxidative stress, resulting in osteoblast apoptosis, largely contributes to abnormal bone remodeling. Melatonin (MT) synthesized by the pineal gland promotes osteoblast differentiation and bone formation and has been effectively used to combat oxidative stress. Therefore, we hypothesized that MT attenuates osteoblast apoptosis induced by oxidative stress, promotes osteogenesis in osteoporosis, and improves bone mass around prostheses. Moreover, considering the distribution and metabolism of MT, its systemic administration would require a large amount of MT, increasing the probability of drug side effects, so the local administration of MT is more effective than its systemic administration. In this study, we constructed a composite adhesive hydrogel system (GelMA-DOPA@MT) to bring about sustained MT release in a local area. Additionally, MT-reduced apoptosis caused by hydrogen peroxide- (H2O2-) induced oxidative stress and restored the osteogenic potential of MC3T3-E1 cells. Furthermore, apoptosis in osteoblasts around the implant was significantly attenuated, and increased bone mass around the implant was observed in ovariectomized (OVX) rats treated with this composite system. In conclusion, our results show that GelMA-DOPA@MT can inhibit osteoblast apoptosis caused by oxidative stress, thereby promoting osteogenesis and improving bone quality around a prosthesis. Therefore, this system of local, sustained MT release is a suitable candidate to address implant loosening in patients with osteoporosis.

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“…In this study, we found that conductive hydrogels significantly aggravated the inflammation after acute SCI by increasing the proportion of M1 microglia and increased the number of CD68positive microglia in comparison with that in the SCI group 7 days post-surgery. Microglia mediated-inflammation contributes to adverse host immune effects and can lead to the rejection of transplanted biomaterials used for SCI repair [32]. Recent studies suggest that the inflammation microenvironment of the injured spinal cord contributes to the transformation of antiinflammatory M2 microglia into pro-inflammatory M1 microglia shortly after injury and can last for weeks or months, which can act as a barrier to neural regeneration [33,34].…”

Section: Discussionmentioning

confidence: 99%

Exosome-loaded conductive hydrogel with immune-modulating and neurogenesis-enhancing properties for synergistic spinal cord injury repair

Li¹,

Liu²,

Chen³

et al. 2020

Preprint

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Conductive hydrogels are very attractive candidates for accelerated spinal cord injury (SCI) repair because they match the electrical and mechanical properties of neural tissue. However, conductive hydrogel implantation can potentially aggravate inflammation, and hinder its repair efficacy. Bone marrow stem cell-derived exosomes (BMSC-exos) have shown immunomodulatory and tissue regeneration effects, therefore, we developed neural tissue-like conductive hydrogels loaded with BMSC-exos for the synergistic treatment of SCI. These exos-loaded conductive hydrogels modulated microglial M2 polarization via the NF-κB pathway, and synergistically enhanced neuronal and oligodendrocyte differentiation of neural stem cells (NSCs) while inhibiting astrocyte differentiation, and also increased axon outgrowth via the PTEN/PI3K/AKT/mTOR pathway. Furthermore, exos combined conductive hydrogels significantly decreased the number of CD68-positive microglia, enhanced local neurogenesis, and promoted axonal regeneration, resulting in significant functional recovery at the early stage in an SCI mouse model. Hence, the findings of this study demonstrate that the combination of conductive hydrogels and BMSC-exos is a promising therapeutic strategy for SCI repair.

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A novel hydrogel-based treatment for complete transection spinal cord injury repair is driven by microglia/macrophages repopulation

Cited by 84 publications

References 75 publications

Irisin Protects Against Motor Dysfunction of Rats with Spinal Cord Injury via Adenosine 5'-Monophosphate (AMP)-Activated Protein Kinase-Nuclear Factor Kappa-B Pathway

Irisin Protects Against Motor Dysfunction of Rats with Spinal Cord Injury via Adenosine 5'-Monophosphate (AMP)-Activated Protein Kinase-Nuclear Factor Kappa-B Pathway

Sustained Release of Melatonin from GelMA Liposomes Reduced Osteoblast Apoptosis and Improved Implant Osseointegration in Osteoporosis

Exosome-loaded conductive hydrogel with immune-modulating and neurogenesis-enhancing properties for synergistic spinal cord injury repair

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