scholarly journals Integrated printed BDNF/collagen/chitosan scaffolds with low temperature extrusion 3D printer accelerated neural regeneration after spinal cord injury

2021 ◽  
Author(s):  
Xiao-Yin Liu ◽  
Chong Chen ◽  
Hai-Huan Xu ◽  
Yu-sheng Zhang ◽  
Lin Zhong ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Biological Activity ◽  
Growth Factors ◽  
3D Printing ◽  
Low Temperature ◽  
Neural Regeneration ◽  
Injury Site ◽  
Locomotor Function ◽  
Cord Injury ◽  
Chitosan Scaffolds

Abstract Recent studies have shown that 3D printed scaffolds integrated with growth factors can guide the growth of neurites and promote axon regeneration at the injury site. However, heat, organic solvents or cross-linking agents used in conventional 3D printing reduce the biological activity of growth factors. Low temperature 3D printing can incorporate growth factors into the scaffold and maintain their biological activity. In this study, we developed a collagen/chitosan scaffold integrated with brain-derived neurotrophic factor (3D-CC-BDNF) by low temperature extrusion 3D printing as a new type of artificial controlled release system, which could prolong the release of BDNF for the treatment of SCI. 8 weeks after the implantation of scaffolds in the transected lesion of T10 of the spinal cord, 3D-CC-BDNF significantly ameliorate locomotor function of the rats. Consistent with the recovery of locomotor function, 3D-CC-BDNF treatment could fill the gap, facilitate nerve fiber regeneration, accelerate the establishment of synaptic connections and enhance remyelination at the injury site.

Inhibition of x-irradiation–enhanced locomotor recovery after spinal cord injury by hyperbaric oxygen or the antioxidant nitroxide tempol

2007 ◽  
Vol 6 (4) ◽  
pp. 337-343 ◽  
Author(s):  
Virany H. Hillard ◽  
Hong Peng ◽  
Kaushik Das ◽  
Raj Murali ◽  
Chitti R. Moorthy ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Hyperbaric Oxygen ◽  
Spinal Cord Tissue ◽  
Irradiation Site ◽  
Injury Site ◽  
Locomotor Recovery ◽  
Locomotor Function ◽  
Cord Injury ◽  
X Irradiation

Object Hyperbaric oxygen (HBO), the nitroxide antioxidant tempol, and x-irradiation have been used to promote locomotor recovery in experimental models of spinal cord injury. The authors used x-irradiation of the injury site together with either HBO or tempol to determine whether combined therapy offers greater benefit to rats. Methods Contusion injury was produced with a weight-drop device in rats at the T-10 level, and recovery was determined using the 21-point Basso-Beattie-Bresnahan (BBB) locomotor scale. Locomotor function recovered progressively during the 6-week postinjury observation period and was significantly greater after x-irradiation (20 Gy) of the injury site or treatment with tempol (275 mg/kg intraperitoneally) than in untreated rats (final BBB Scores 10.6 [x-irradiation treated] and 9.1 [tempol treated] compared with 6.4 [untreated], p < 0.05). Recovery was not significantly improved by HBO (2 atm for 1 hour [BBB Score 8.2, p > 0.05]). Interestingly, the improved recovery of locomotor function after x-irradiation, in contrast with antiproliferative radiotherapy for neoplasia, was inhibited when used together with either HBO or tempol (BBB Scores 8.2 and 8.3, respectively). The ability of tempol to block enhanced locomotor recovery by x-irradiation was accompanied by prevention of alopecia at the irradiation site. The extent of locomotor recovery following treatment with tempol, HBO, and x-irradiation correlated with measurements of spared spinal cord tissue at the contusion epicenter. Conclusions These results suggest that these treatments, when used alone, can activate neuroprotective mechanisms but, in combination, may result in neurotoxicity.

scholarly journals The Potential for Cellular Therapy Combined with Growth Factors in Spinal Cord Injury

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Jack Rosner ◽  
Pablo Avalos ◽  
Frank Acosta ◽  
John Liu ◽  
Doniel Drazin
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Growth Factors ◽  
Cellular Therapy ◽  
Embryonic Stem ◽  
Neural Regeneration ◽  
Functional Improvement ◽  
Combination Therapies ◽  
Cord Injury

Any traumatic spinal cord injury (SCI) may cause symptoms ranging from pain to complete loss of motor and sensory functions below the level of the injury. Currently, there are over 2 million SCI patients worldwide. The cost of their necessary continuing care creates a burden for the patient, their families, and society. Presently, few SCI treatments are available and none have facilitated neural regeneration and/or significant functional improvement. Research is being conducted in the following areas: pathophysiology, cellular therapies (Schwann cells, embryonic stem cells, induced pluripotent stem cells, mesenchymal stem cells, olfactory ensheathing cells), growth factors (BDNF), inhibitory molecules (NG2, myelin protein), and combination therapies (cell grafts and neurotrophins, cotransplantation). Results are often limited because of the inhibitory environment created following the injury and the limited regenerative potential of the central nervous system. Therapies that show promise in small animal models may not transfer to nonhuman primates and humans. None of the research has resulted in remarkable improvement, but many areas show promise. Studies have suggested that a combination of therapies may enhance results and may be more effective than a single therapy. This paper reviews and discusses the most promising new SCI research including combination therapies.

scholarly journals Minocycline Enhance Restorative Ability of Olfactory Ensheathing Cells by Upregulation of BDNF and GDNF Expression After Spinal Cord Injury

2021 ◽  
Author(s):  
Soheila Pourkhodadad ◽  
◽  
Shahrbanoo Oryan ◽  
Mohammadmehdi Hadipour ◽  
Gholamreza Kaka ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Neurotrophic Factor ◽  
Axon Growth ◽  
Female Rats ◽  
Olfactory Ensheathing Cells ◽  
Injury Site ◽  
Locomotor Function ◽  
Cord Injury ◽  
Ensheathing Cells

Purpose: Spinal cord injury is a global public health issue that results in extensive neuronal degeneration, axonal and myelin loss and severe functional deficits. Neurotrophic factors are potential treatment for reducing secondary damage, promoting axon growth, and are responsible for inducing myelination after injury. Olfactory ensheathing cells (OECs) and minocycline have been shown to promote locomotor function after spinal cord injury. In the present study, we investigated the neuroprotective effects of combined treatment with minocycline and OECs on the spinal cord injury in relation with brain-derived neurotrophic factor (BDNF) and glial derived neurotrophic factor (GDNF) expressions after SCI. Methods: Adult female rats were used to experimental SCI by weight compression method. Rats received intraperitoneal injection of minocycline (90 mg/kg) immediately after SCI and then 24 h after injury. OECs were transplanted one week after the injury. The hindlimb function was assessed using Basso Beattie Bresnahan (BBB) locomotor rating scale and electromyography (EMG). After five weeks, the segment of the spinal cord centered at the injury site was removed for histopathological analysis. Immunohistological and western blot assays were performed to observe the expression of NeuN, BDNF, GDNF and myelin basic protein (MBP). Results: SCI induced loss of locomotor function with decreased BDNF and GDNF expressions in the injury site. Minocycline +OECs increased the score of BBB locomotor scale and increased spared tissue in the injury site. Immunohistochemical results showed NeuN expression significantly increased in minocycline + OECs group than other groups. Also electromyography amplitude in treated rats was increased compared to control group. BDNF, GDNF and MBP expressions and the number of ventral motor neurons increased further by minocycline + OECs in SCI rats. Conclusion: The present study provides the evidence that minocycline may facilitate recovery of locomotor function by OECs through increasing of BDNF and GDNF expressions following SCI.

Fibrin scaffolds embedded with sonic hedgehog/chitosan microspheres for recovery of spinal cord injury in rats

2020 ◽  
Vol 10 (3) ◽  
pp. 437-445 ◽  
Author(s):  
Wenjing Yang ◽  
Zhe Wang ◽  
Jingxin Zhang ◽  
Kaiyuan Yang ◽  
Cong Lu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Biological Activity ◽  
Motor Function ◽  
Sonic Hedgehog ◽  
Nerve Fibers ◽  
Injury Site ◽  
Cord Injury ◽  
Recovery Of Motor Function

Sonic hedgehog (SHH) has been shown to exert a protection on promoting the spinal cord injury (SCI) recovery, but it can’t remain with its biological activity and sustained release at the injury site for long-term application. Herein, fibrin scaffolds embedded with SHH-loaded chitosan (CS) microspheres (SHH/CS) were synthesized and applied to provide protection and regeneration for complete transected spinal cord in rats. Characteristics of fibrin scaffolds embedded with SHH/CS microspheres, histological studies, immunohistochemistry staining, Western Blotting and recovery of motor function were conducted after implantation, respectively. Result showed that SHH maintained its biological activity and continued to act at the injury site, and the fibrin scaffolds embedded with SHH/CS microspheres could protect neurons and reduce apoptosis in the in vivo study, it also promoted some nerve fibers cross the spinal cord injury area. Moreover, the scaffolds improved partial motor function of double-hindlimb on a macro level. Overall, the fibrin scaffolds embedded with SHH/CS microspheres showed more satisfactory effect on nerve regeneration, tissue cavities prevention and motor function improvement, compared to fibrin scaffolds with SHH directly encapsulated into or fibrin scaffolds alone.

Genetic Ablation of Transcription Repressor Bach1 Reduces Neural Tissue Damage and Improves Locomotor Function after Spinal Cord Injury in Mice

2009 ◽  
Vol 26 (1) ◽  
pp. 31-39 ◽  
Author(s):  
Haruo Kanno ◽  
Hiroshi Ozawa ◽  
Yoshihiro Dohi ◽  
Akira Sekiguchi ◽  
Kazuhiko Igarashi ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Tissue Damage ◽  
Neural Tissue ◽  
Locomotor Function ◽  
Genetic Ablation ◽  
Cord Injury

scholarly journals Biomaterial Approaches to Modulate Reactive Astroglial Response

2018 ◽  
Vol 205 (5-6) ◽  
pp. 372-395 ◽  
Author(s):  
Jonathan M. Zuidema ◽  
Ryan J. Gilbert ◽  
Manoj K. Gottipati
Keyword(s):  
Spinal Cord ◽  
Glial Scar ◽  
Secondary Injury ◽  
Injury Site ◽  
Beneficial Effects ◽  
Cord Injury ◽  
The Central Nervous System ◽  
Preclinical Animal Models

Over several decades, biomaterial scientists have developed materials to spur axonal regeneration and limit secondary injury and tested these materials within preclinical animal models. Rarely, though, are astrocytes examined comprehensively when biomaterials are placed into the injury site. Astrocytes support neuronal function in the central nervous system. Following an injury, astrocytes undergo reactive gliosis and create a glial scar. The astrocytic glial scar forms a dense barrier which restricts the extension of regenerating axons through the injury site. However, there are several beneficial effects of the glial scar, including helping to reform the blood-brain barrier, limiting the extent of secondary injury, and supporting the health of regenerating axons near the injury site. This review provides a brief introduction to the role of astrocytes in the spinal cord, discusses astrocyte phenotypic changes that occur following injury, and highlights studies that explored astrocyte changes in response to biomaterials tested within in vitro or in vivo environments. Overall, we suggest that in order to improve biomaterial designs for spinal cord injury applications, investigators should more thoroughly consider the astrocyte response to such designs.

scholarly journals pH-responsive delivery of H2 through ammonia borane-loaded mesoporous silica nanoparticles improves recovery after spinal cord injury by moderating oxidative stress and regulating microglial polarization

2021 ◽  
Author(s):  
Yi Liu ◽  
Yeying Wang ◽  
Bing Xiao ◽  
Guoke Tang ◽  
Jiangming Yu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Mesoporous Silica ◽  
Silica Nanoparticles ◽  
Mesoporous Silica Nanoparticles ◽  
Ammonia Borane ◽  
Neural Regeneration ◽  
Dependent Manner ◽  
Cord Injury

Abstract Imbalance of oxidative and inflammatory regulation is the main contributor to neurofunctional deterioration and failure of rebuilding spared neural networks after spinal cord injury (SCI). As an emerging biosafe strategy for protecting against oxidative and inflammatory damage, hydrogen (H2) therapy is a promising approach for improving the microenvironment to allow neural regeneration. However, achieving release of H2 at sufficient concentrations specifically into the injured area is critical for the therapeutic effect of H2. Thus, we assembled SiO2@mSiO2 mesoporous silica nanoparticles and loaded them with ammonia borane (AB), which has abundant capacity and allows controllable release of H2 in an acid-dependent manner. The release of H2 from AB/SiO2@mSiO2 was satisfactory at pH 6.6, which is approximately equal to the microenvironmental acidity after SCI. After AB/SiO2@mSiO2 were intrathecally administered to rat models of SCI, continuous release of H2 from these nanoparticles synergistically enhanced neurofunctional recovery, reduced fibrotic scar formation and promoted neural regeneration by suppressing oxidative stress reaction. Furthermore, in the subacute phase of SCI, microglia were markedly polarized toward the M2 phenotype by H2 via inhibition of TLR9 expression in astrocytes. In conclusion, H2 delivery through AB/SiO2@mSiO2 has the potential to efficiently treat SCI through comprehensive modulation of the oxidative and inflammatory imbalance in the microenvironment.

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