Graft of the NT-3 persistent delivery gelatin sponge scaffold promotes axon regeneration, attenuates inflammation, and induces cell migration in rat and canine with spinal cord injury

Li, Ge; Che, Ming-Tian; Zhang, Ke; Qin, Lanfang; Zhang, Yuting; Chen, Ruiqiang; Rong, Limin; Liu, Shu; Ding, Ying; Shen, Huiyong; Long, Simei; Wu, Jin-Lang; Ling, Eng‐Ang; Zeng, Yuan-Shan

doi:10.1016/j.biomaterials.2015.11.059

Cited by 110 publications

(99 citation statements)

References 67 publications

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“…It has been reported that electrical stimulation can increase the expression of NT‐3 in the lumbar motor neurons and alleviate the muscle atrophy in the hindlimb, which will allow for the new treatment strategy in the injured spinal cord 54. In accordance with our previous work,12 we have provided here with further evidence that supports the use of bioactive scaffold to reform central pattern‐generating circuitry of spinal interneurons in canines. Similar to using genetically engineered to delivery NT‐3,11 bioactive scaffolds are evidently beneficial to improve post‐injury environment and to circumvent the risk of virus transmission.…”

Section: Discussionsupporting

confidence: 89%

“…Here, we have compared the ground forces applied by the two hindlimbs and used force differences of gait between the limbs to estimate recovery. A similar Olby score was used in our previous study which reflected the effectiveness of the treatment for SCI 8, 12. With NT‐3 delivery, canines showed excellent CMEP and coordinate limb movement.…”

Section: Discussionmentioning

confidence: 93%

“…The methods for the preparation of NF‐GS scaffolds have been described in detail in our previous study 12. Briefly, sterile gelatin sponge (GS) scaffolds were tailored into a “D” shape tube with a diameter of 2 mm and a length of 4 mm, submerged in NT‐3/fibroin (NF) particle solution completely and wrapped up with poly‐lactic‐ co ‐glycolicacid (PLGA) tubes.…”

Section: Methodsmentioning

confidence: 99%

“…This had prompted us to design a novel bioactive scaffold for the delivery of NT‐3 by using the NT‐3/fibroin particles as surface decoration. The gelatin sponge (NF‐GS) scaffold coated with NT‐3/fibroin particles had achieved a controlled artificial release system, thus providing significant therapeutic effects on nerve fiber regeneration and inflammatory inhibition in the rat SCI model 12. The functional recovery after SCI maybe dependent on several factors: (1) Attenuation of physical (such as cavities13) and biochemical (such as glial scars14 and inflammatory cytokines/cells15) barriers in the microenvironment, (2) Cytoarchitecture reshaping with functional neurogenesis, synaptogenesis, angiogenesis and remyelination at the injury site16, 17 and (3) Motor function restoration as manifested by improved electrophysiological recording18 and locomotion performance.…”

Section: Introductionmentioning

confidence: 99%

“…This method for the treatment of spinal cord injury obviated the risk of insecurity by gene transfer techniques and of uncertain survival by cell transplantation. More importantly, it showed regeneration of functional neuronal axons, reduction of cavity formation, and remyelination of rats through the scaffold transplantation 12. However, there was still lack of a concrete electrophysiological evidence to prove whether the bioactive scaffold plays a critical role as nutrient enrichment region to enhance endogenous regeneration.…”

Section: Introductionmentioning

confidence: 99%

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Neurotrophin‐3 released from implant of tissue‐engineered fibroin scaffolds inhibits inflammation, enhances nerve fiber regeneration, and improves motor function in canine spinal cord injury

Che

Zeng

et al. 2018

J Biomedical Materials Res

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Spinal cord injury (SCI) normally results in cell death, scarring, cavitation, inhibitory molecules release, etc., which are regarded as a huge obstacle to reconnect the injured neuronal circuits because of the lack of effective stimulus. In this study, a functional gelatin sponge scaffold was used to inhibit local inflammation, enhance nerve fiber regeneration, and improve neural conduction in the canine. This scaffold had good porosity and modified with neurotrophin‐3 (NT‐3)/fibroin complex, which showed sustained release in vitro. After the scaffold was transplanted into canine spinal cord hemisection model, hindlimb movement, and neural conduction were improved evidently. Migrating host cells, newly formed neurons with associated synaptic structures together with functional blood vessels with intact endothelium in the regenerating tissue were identified. Taken together, the results demonstrated that using bioactive scaffold could establish effective microenvironment stimuli for endogenous regeneration, providing a potential and practical strategy for treatment of spinal cord injury. © 2018 The Authors Journal of Biomedical Materials Research Part A Published by Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2158‐2170, 2018.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 93%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Neurotrophin‐3 released from implant of tissue‐engineered fibroin scaffolds inhibits inflammation, enhances nerve fiber regeneration, and improves motor function in canine spinal cord injury

Che

Zeng

et al. 2018

J Biomedical Materials Res

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Role of Trichocytic Keratins in Anti‐Neuroinflammatory Effects After Spinal Cord Injury

Zhong

Shi

Zhou

et al. 2023

Adv Funct Materials

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Shifting microglia/macrophages to M2 anti-inflammatory phenotype is considered a pivotal therapeutic target for spinal cord injury (SCI). Keratin extracted from human hair exhibits anti-inflammatory properties. However, the differences among the 17 types of human hair keratins and their mechanisms of anti-inflammation remain poorly understood. In this study, the anti-inflammatory activity of 17 human hair keratins using a recombinant synthesis approach is explored. Distinct activities of microglia/macrophage phenotype modulation of 17 keratins are found through qRT-PCR analysis, and recombinant keratin 33A (RK33A) and RK35 display superior anti-inflammatory efficiency compared to other keratins. Immunofluorescence and flow cytometry reveals a significant effect of RK33A on the regulation of microglia/macrophages into an anti-inflammatory M2 phenotype. Subsequently, recombinant keratin 33A nanofiber (RKNF33A) is fabricated to evaluate its in vivo anti-inflammatory and nerve regeneration properties using the rat T9 spinal cord lateral hemisection model. The optimized keratin-based nanofiber shows outstanding performance in enhancing M2 polarization, reducing glial scarring, promoting nerve regeneration, and improving locomotor function recovery in SCI rats. Moreover, it is preliminarily found that RK33A regulates M2 microglia/macrophage polarization by upregulating the PI3K/AKT/mTOR signaling pathway. Together, this study reveals that trichocytic keratins exhibit distinct anti-inflammatory properties, providing a prospective treatment for SCI by modulating microglia/macrophage polarization.

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Biomaterial‐Based Defenders Boost Biopharmaceuticals Efficacy for Spinal Cord Injury Treatment: A Review

Zhang

Cao

2023

Adv Materials Inter

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Spinal cord injury (SCI) has seriously affected the lives of patients and brought economic and medical burdens to society. Biopharmaceuticals, including transplanted cells, growth factors, enzyme drugs, and microRNA, present multidimensional therapeutic effects in tissue repair and regeneration, and thus are widely utilized for the treatment of SCI. Nevertheless, they still encounter great challenges. The turbulent microenvironment accompanied by various destructive components following SCI has led to poor stability, low local accumulation, and reduced therapeutic efficacy of biopharmaceuticals. To this end, biomaterial‐based defenders (BBDs) that are capable of resisting the destructive components have shown great promise in improving the survival of transplanted cells or retaining the activity of the protein and nucleic acid drugs for the treatment of SCI. In this review, various types of biopharmaceuticals applied in SCI and their limitations are introduced. The destructive components that threaten the activities of biopharmaceuticals in the rigorous microenvironment are then summarized. In particular, the current research progress about BBDs boosting the efficacy of biopharmaceuticals for the treatment of SCI is illustrated with specific examples. The existing challenges and future perspectives are also provided.

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Graft of the NT-3 persistent delivery gelatin sponge scaffold promotes axon regeneration, attenuates inflammation, and induces cell migration in rat and canine with spinal cord injury

Cited by 110 publications

References 67 publications

Neurotrophin‐3 released from implant of tissue‐engineered fibroin scaffolds inhibits inflammation, enhances nerve fiber regeneration, and improves motor function in canine spinal cord injury

Neurotrophin‐3 released from implant of tissue‐engineered fibroin scaffolds inhibits inflammation, enhances nerve fiber regeneration, and improves motor function in canine spinal cord injury

Role of Trichocytic Keratins in Anti‐Neuroinflammatory Effects After Spinal Cord Injury

Biomaterial‐Based Defenders Boost Biopharmaceuticals Efficacy for Spinal Cord Injury Treatment: A Review

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