Long-lasting significant functional improvement in chronic severe spinal cord injury following scar resection and polyethylene glycol implantation

Estrada, Veronica; Brazda, Nicole; Schmitz, Christine; Heller, Silja; Blazyca, Heinrich; Martini, Rudolf; Müller, Hans

doi:10.1016/j.nbd.2014.03.018

Cited by 77 publications

(129 citation statements)

References 62 publications

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“…Blood vessels are required for the provision of nutrients and removal of waste products, processes that are vital for tissue regeneration (Owen and Shoichet, 2010). Angiogenesis and vascularization of the scaffold implant have been reported for numerous neural ECM biomaterials (Bakshi et al, 2004;Bramfeldt et al, 2010;Estrada et al, 2014;Plant et al, 1997;Woerly et al, 1999).…”

Section: Interaction Of Ecm Scaffold and Host Ecmmentioning

confidence: 99%

“…This feature is especially useful when ECM scaffolds are required to bridge tissue defects, which are often irregularly shaped (Estrada et al, 2014;Jain et al, 2006;Sakiyama-Elbert et al, 2012). However, although hydrogels are considered as suitable ECM mimetic substrates whose porosity ensures the supply with nutrients, growth factors, and oxygen to the cell, their porous nature is also disadvantageous.…”

Section: Ecm Mimeticsmentioning

confidence: 99%

“…In regeneration studies, alginate gels are often applied as cell carrier substances. Alginate has been described to enhance neuronal sprouting and to decrease inhibitory cues after CNS trauma (Kataoka et al, 2004;Prang et al, 2006), but other studies have also reported a lack of axon growth stimulation mediated by alginate scaffolds (Estrada et al, 2014;Novikova et al, 2006). In vitro studies have even demonstrated that this biomaterial can inhibit the growth of dorsal root ganglion neurons and cause alteration of the phenotype of various different cell types (Novikova et al, 2006).…”

Section: Alginatementioning

confidence: 99%

“…It has been described as a suitable matrix for tissue generation (Cassell et al, 2001) and has led to neuronal regeneration of varying degrees from only limited growth to extensive axonal sprouting in several studies (Iannotti et al, 2003;Novikova et al, 2006). Scaffolds of Matrigel ™ allow only limited axonal growth after spinal cord trauma (Estrada et al, 2014;Sakiyama-Elbert et al, 2012;Someya et al, 2008). This ECM mimetic, however, seems to exert significant beneficial, growth-promoting effects when it is used as a cell carrier medium in cell transplantation studies.…”

Section: Matrigelmentioning

confidence: 99%

“…Beneficial effects of a PEG biopolymer matrix have been described recently. In the respective study, a solution of pure PEG 600 was applied after resection of spinal scar tissue in rats with severe chronic spinal cord injury (Estrada et al, 2014). Although PEG polymers per se do not conform to the basic requirement of an ECM mimetic, which is to provide structural support, they nevertheless promote the formation of a beneficial stable microenvironment in vivo.…”

Section: Polyethylene Glycolmentioning

confidence: 99%

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Neural ECM mimetics

Estrada

Tekinay

Müller

2014

Progress in Brain Research

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The consequence of numerous neurological disorders is the significant loss of neural cells, which further results in multilevel dysfunction or severe functional deficits. The extracellular matrix (ECM) is of tremendous importance for neural regeneration mediating ambivalent functions: ECM serves as a growth-promoting substrate for neurons but, on the other hand, is a major constituent of the inhibitory scar, which results from traumatic injuries of the central nervous system. Therefore, cell and tissue replacement strategies on the basis of ECM mimetics are very promising therapeutic interventions. Numerous synthetic and natural materials have proven effective both in vitro and in vivo. The closer a material's physicochemical and molecular properties are to the original extracellular matrix, the more promising its effectiveness may be. Relevant factors that need to be taken into account when designing such materials for neural repair relate to receptor-mediated cell-matrix interactions, which are dependent on chemical and mechanical sensing. This chapter outlines important characteristics of natural and synthetic ECM materials (scaffolds) and provides an overview of recent advances in design and application of ECM materials for neural regeneration, both in therapeutic applications and in basic biological research.

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Section: Interaction Of Ecm Scaffold and Host Ecmmentioning

confidence: 99%

Section: Ecm Mimeticsmentioning

confidence: 99%

Section: Alginatementioning

confidence: 99%

Section: Matrigelmentioning

confidence: 99%

Section: Polyethylene Glycolmentioning

confidence: 99%

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Neural ECM mimetics

Estrada

Tekinay

Müller

2014

Progress in Brain Research

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Cell and Tissue Instructive Materials for Central Nervous System Repair

Rocha

Silva

Barata‐Antunes

et al. 2020

Adv Funct Materials

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Neurodegenerative disorders and traumatic events affecting the central nervous system (CNS) represent one of the main health problems nowadays. The level of disability and impairment of these patients is very high, both at physiological and psychological level, drastically altering a person's lifestyle. The fact that CNS tissue has a limited capacity of regeneration has hampered the development of possible therapies to these conditions. The specificity of each disease also increases the complexity of creating strategies capable of inducing significant recovery. Therefore, the search for a solution for these problems most likely demands a combinatorial approach that integrates knowledge from different fields. Tissue engineering and regenerative medicine (TERM) concepts merge areas such as biology, chemistry, physics, or biomaterials science, and it is a strong candidate for CNS applications. In particular, the development of cell and tissue instructive materials (CTIMs) can bring new opportunities for the treatment of these conditions. In this review, the authors summarize and discuss the most recent advances in the development of CTIMs for CNS applications, focusing on traumatic conditions such as spinal cord injuy, traumatic brain injuy, but also stroke, and other neurodegenerative diseases such as Alzheimer's and Parkinson's disease as well as multiple sclerosis.

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Sustained Release of Human Adipose Tissue Stem Cell Secretome from Star‐Shaped Poly(ethylene glycol) Glycosaminoglycan Hydrogels Promotes Motor Improvements after Complete Transection in Spinal Cord Injury Rat Model

Silva

Schirmer

Pinho

et al. 2023

Adv Healthcare Materials

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Adipose tissue‐derived stem cells (ASCs) have been shown to assist regenerative processes after spinal cord injury (SCI) through their secretome, which promotes several regenerative mechanisms, such as inducing axonal growth, reducing inflammation, promoting cell survival, and vascular remodeling, thus ultimately leading to functional recovery. However, while systemic delivery (e.g., i.v. [intravenous]) may cause off‐target effects in different organs, the local administration has low efficiency due to fast clearance by body fluids. Herein, a delivery system for human ASCs secretome based on a hydrogel formed of star‐shaped poly(ethylene glycol) (starPEG) and the glycosaminoglycan heparin (Hep) that is suitable to continuously release pro‐regenerative signaling mediators such as interleukin (IL)‐4, IL‐6, brain‐derived neurotrophic factor, glial‐cell neurotrophic factor, and beta‐nerve growth factor over 10 days, is reported. The released secretome is shown to induce differentiation of human neural progenitor cells and neurite outgrowth in organotypic spinal cord slices. In a complete transection SCI rat model, the secretome‐loaded hydrogel significantly improves motor function by reducing the percentage of ameboid microglia and systemically elevates levels of anti‐inflammatory cytokines. Delivery of ASC‐derived secretome from starPEG‐Hep hydrogels may therefore offer unprecedented options for regenerative therapy of SCI.

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Long-lasting significant functional improvement in chronic severe spinal cord injury following scar resection and polyethylene glycol implantation

Cited by 77 publications

References 62 publications

Neural ECM mimetics

Neural ECM mimetics

Cell and Tissue Instructive Materials for Central Nervous System Repair

Sustained Release of Human Adipose Tissue Stem Cell Secretome from Star‐Shaped Poly(ethylene glycol) Glycosaminoglycan Hydrogels Promotes Motor Improvements after Complete Transection in Spinal Cord Injury Rat Model

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