Mesenchymal stem cells encapsulated into biomimetic hydrogel scaffold gradually release CCL2 chemokine in situ preserving cytoarchitecture and promoting functional recovery in spinal cord injury

Papa, Simonetta; Vismara, Irma; Mariani, Alessandro; Barilani, Mario; Rimondo, Stefano; Paola, Massimiliano De; Panini, Nicolò; Erba, Eugenio; Mauri, Emanuele; Rossi, Filippo; Forloni, Gianluigi; Lazzari, Lorenza; Veglianese, Pietro

doi:10.1016/j.jconrel.2018.03.034

Cited by 90 publications

(78 citation statements)

References 36 publications

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“…The TOUS-CNFs obtained are of about 10 nanometers width and a length in the range of 200-400 nm (Figure 2a), in line with data reported in the literature [15,16]. It has been reported how aqueous dispersions of these nanofibers exhibit rheological properties typical of thixotropic materials [28].…”

Section: Rheological Propertiessupporting

confidence: 89%

“…The versatility of hydrogels allows for their fabrication, with embedded cells, by different technologies, including wet spinning [8], 3D printing [9], microspheres [10], and microfluidics [11]. In particular, injectable hydrogels have recently been gaining increasing interest regarding the localized introduction of small functional molecules for diagnostic purposes [12], for drug release and delivery [13] or injection of stem cells in regenerative therapy [14,15]. In this context, the investigation of the cyto/biocompatibility of novel hydrogels becomes crucial in order to propose them for biomedical applications.…”

Section: Introductionmentioning

confidence: 99%

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TEMPO-Nanocellulose/Ca2+ Hydrogels: Ibuprofen Drug Diffusion and In Vitro Cytocompatibility

et al. 2020

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Stable hydrogels with tunable rheological properties were prepared by adding Ca2+ ions to aqueous dispersions of 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO)-oxidized and ultra-sonicated cellulose nanofibers (TOUS-CNFs). The gelation occurred by interaction among polyvalent cations and the carboxylic units introduced on TOUS-CNFs during the oxidation process. Both dynamic viscosity values and pseudoplastic rheological behaviour increased by increasing the Ca2+ concentration, confirming the cross-linking action of the bivalent cation. The hydrogels were proved to be suitable controlled release systems by measuring the diffusion coefficient of a drug model (ibuprofen, IB) by high-resolution magic angle spinning (HR-MAS) nuclear magnetic resonance (NMR) spectroscopy. IB was used both as free molecule and as a 1:1 pre-formed complex with β-cyclodextrin (IB/β-CD), showing in this latter case a lower diffusion coefficient. Finally, the cytocompatibility of the TOUS-CNFs/Ca2+ hydrogels was demonstrated in vitro by indirect and direct tests conducted on a L929 murine fibroblast cell line, achieving a percentage number of viable cells after 7 days higher than 70%.

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Section: Rheological Propertiessupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

TEMPO-Nanocellulose/Ca2+ Hydrogels: Ibuprofen Drug Diffusion and In Vitro Cytocompatibility

et al. 2020

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“…Drug delivery remains the main challenge of SCI drug development due to the fast metabolism and/or rapid blood clearance of most SCI drugs, as well as poor diffusion through the blood-spinal cord barrier (BSCB) [43]. It has been suggested that nanotechnologies may promote spinal cord delivery and efficacy of drugs because of an improved pharmacokinetic profile and better neurovascular unit access [12,[24][25][26][27]. However, many of these nanocarriers require complex functional design to achieve targeted delivery of drugs which may restrain their pharmaceutical development [44].…”

Section: Discussionmentioning

confidence: 99%

“…In the past decade, several studies have reported the application of nanoparticles for treatment of SCI [12,[24][25][26][27]. Compared with other nanoparticles, mesoporous silica nanoparticles (MSNs) have shown significant benefits as a drug delivery system over traditional drug nanocarriers due to their tailored mesoporous structure and high surface area [28,29].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Characterization of a Silica-Based Drug Delivery System for Spinal Cord Injury Therapy

et al. 2019

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Acute inflammation is a central component in the progression of spinal cord injury (SCI). Anti-inflammatory drugs used in the clinic are often administered systemically at high doses, which can paradoxically increase inflammation and result in drug toxicity. A cluster-like mesoporous silica/arctigenin/CAQK composite (MSN-FC@ARC-G) drug delivery system was designed to avoid systemic side effects of high-dose therapy by enabling site-specific drug delivery to the spinal cord. In this nanosystem, mesoporous silica was modified with the FITC fluorescent molecule and CAQK peptides that target brain injury and SCI sites. The size of the nanocarrier was kept at approximately 100 nm to enable penetration of the blood–brain barrier. Arctigenin, a Chinese herbal medicine, was loaded into the nanosystem to reduce inflammation. The in vivo results showed that MSN-FC@ARC-G could attenuate inflammation at the injury site. Behavior and morphology experiments suggested that MSN-FC@ARC-G could diminish local microenvironment damage, especially reducing the expression of interleukin-17 (IL-17) and IL-17-related inflammatory factors, inhibiting the activation of astrocytes, thus protecting neurons and accelerating the recovery of SCI. Our study demonstrated that this novel, silica-based drug delivery system has promising potential for clinical application in SCI therapy.

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“…The lack of neurotrophic factors and glial scarring, together with the neuroinflammation, is considered to be crucial targets for the reconstruction of functional connections [62]. Co-transplantation of biomaterial and MSCs, which are manipulated or genetically edited to express certain proteins, exerts neuroprotective, and anti-inflammatory effects to induce anti-inflammatory mechanisms [63]. Recently, significant progress has been made to elucidate the pathophysiology of SCI and to uncover the mechanisms that make the injured spinal cord refractory to regeneration.…”

Section: Combination Of Biomaterials and Mscs Improve The Microenvironmentioning

confidence: 99%

Biomaterial-supported MSCs transplantation enhances cell-cell communication for spinal cord injury

Wang

yang

2020

Preprint

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The spinal cord is part of the central nervous system (CNS) and serves to connect the brain to the peripheral nervous system and peripheral tissues. The cell types that primarily comprise the spinal cord are neurons and several categories of glia, including astrocytes, oligodendrocytes, and microglia. Ependymal cells and small populations of endogenous stem cells, such as oligodendrocyte progenitor cells, also reside in the spinal cord [1]. Neurons are interconnected in circuits; those that process cutaneous sensory input are mainly located in the dorsal spinal cord, while those involved in proprioception and motor control are predominately located in the ventral spinal cord [2]. Due to the importance of the spinal cord, neurodegenerative disorders and traumatic injuries affecting the spinal cord will lead to motor deficits and loss of sensory inputs. Spinal cord injury (SCI), resulting in paraplegia and tetraplegia as a result of deleterious interconnected mechanisms encompassed by the primary and secondary injury, represents a heterogeneously behavioral and cognitive deficit that remains incurable. Following SCI, various barriers containing the neuroinflammation, neural tissue defect (neurons, microglia, astrocytes, and oligodendrocytes), cavity formation, loss of neuronal circuitry and function must be overcame[3]. Notably, the pro -inflammatory and anti-inflammatory effect s of cell-cell communication networks play critical roles in homeostatic, driving the pathophysiologic and consequent cognitive outcomes. In the spinal cord, astrocytes, oligodendrocytes and microglia are involved in not only development but also pathology. Glial cells play dual roles (negative vs. positive effects) in these processes. After SCI, detrimental effects usually dominate and significantly retard functional recovery, and curbing these effects is critical for promoting neurological improvement. Indeed, residential innate immune cells (microglia and astrocytes) and infiltrating leukocytes (macrophages and neutrophils), activated by SCI, give rise to full-blown inflammatory cascades. These inflammatory cells release neurotoxins (proinflammatory cytokines and chemokines, free radicals, excitotoxic amino acids, nitric oxide (NO)), all of which partake in axonal and neuronal deficit[4]. Given the various multifaceted obstacles in SCI treatment, a combinatorial therapy of cell transplantation and biomaterial implantation may be addressed in detail here. For the sake of preserving damaged tissue integrity and providing physical support and trophic supply for axon regeneration, MSCs transplantation has come to the front stage in therapy for SCI with the constant progress of stem cell engineering [5]. MSCs transplantation promotes scaffold integration and regenerative growth potential. Integrating into the implanted scaffold, MSCs influences implant integration by improving the healing process[6]. Conversely, biomaterial scaffolds offer MSCs with a sheltered microenvironment from the surrounding pathological changes, in addition to bridging connection spinal cord stump and offering physical and directional support for axonal regeneration. Besides, Biomaterial scaffolds mimic the extracellular matrix to suppress immune responses. Here, we review the advances in combinatorial biomaterial scaffolds and MSCs transplantation approach that targets certain aspects of various intercellular communications in the pathologic process following SCI. Finally, the challenges of biomaterial-supported MSCs transplantation and its future direction for neuronal regeneration will be presented.

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Mesenchymal stem cells encapsulated into biomimetic hydrogel scaffold gradually release CCL2 chemokine in situ preserving cytoarchitecture and promoting functional recovery in spinal cord injury

Cited by 90 publications

References 36 publications

TEMPO-Nanocellulose/Ca2+ Hydrogels: Ibuprofen Drug Diffusion and In Vitro Cytocompatibility

TEMPO-Nanocellulose/Ca2+ Hydrogels: Ibuprofen Drug Diffusion and In Vitro Cytocompatibility

Synthesis and Characterization of a Silica-Based Drug Delivery System for Spinal Cord Injury Therapy

Biomaterial-supported MSCs transplantation enhances cell-cell communication for spinal cord injury

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