Dual-functional hydrogel system for spinal cord regeneration with sustained release of arylsulfatase B alleviates fibrotic microenvironment and promotes axonal regeneration

Park, Hee Hwan; Kim, Young‐Min; Hong, Le Thi Anh; Kim, Hyung Soon; Kim, Sung Hoon; Jin, Xuelian; Hwang, Dae Hyun; Kwon, Min Jung; Song, Soo‐Chang; Kim, Byung Gon

doi:10.1016/j.biomaterials.2022.121526

Cited by 29 publications

(27 citation statements)

References 67 publications

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“…The chondroitin 4-sulfation was recognized as the critically important sulfation. Similar effects of CSPGs were detected after optic nerve injury in rodent models [132].…”

Section: Peripheral Nerve Injurysupporting

confidence: 68%

Profound Impact of Decline in N-Acetylgalactosamine-4-Sulfatase (Arylsulfatase B) on Molecular Pathophysiology and Human Diseases

Tobacman¹,

Bhattacharyya²

2022

Preprint

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The enzyme N-acetylgalactosamine-4-sulfatase (Arylsulfatase B; ARSB) was originally identified as a lysosomal enzyme which was deficient in Mucopolysaccharidosis VI (MPS VI; Maroteaux-Lamy Syndrome). Newly directed attention to the impact of ARSB in human pathobiology indicates a broader, more pervasive effect, encompassing roles as a tumor suppressor, transcriptional mediator, redox switch, and regulator of intracellular and extracellular-cell signaling. By controlling the degradation of chondroitin 4-sulfate and dermatan sulfate by removal or failure to remove the 4-sulfate residue at the non-reducing end of the sulfated glycosaminoglycan chain, ARSB modifies the binding or release of critical molecules into the cell milieu. These molecules, such as galectin-3 and SHP-2, in turn, influence crucial cellular processes and events which determine cell fate. Identification of ARSB at the cell membrane and in the nucleus expands perception of the potential impact of decline in ARSB activity. Regulation of availability of sulfate from chondroitin 4-sulfate and dermatan sulfate may also affect sulfate assimilation and production of vital molecules, including glutathione and cysteine. Increased attention to ARSB in mammalian cells may help to integrate and deepen our understanding of diverse biological phenomenon and to approach human diseases with new insights.

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“…The chondroitin 4-sulfation was recognized as the critically important sulfation. Similar effects of CSPGs were detected after optic nerve injury in rodent models [132].…”

Section: Peripheral Nerve Injurysupporting

confidence: 68%

Profound Impact of Decline in N-Acetylgalactosamine-4-Sulfatase (Arylsulfatase B) on Molecular Pathophysiology and Human Diseases

Tobacman¹,

Bhattacharyya²

2022

Preprint

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“…Recombinant human ARSB was reported to improve functional recovery and eliminated the observed immunoreactivity for chondroitin sulfates within five days. In other experiments, a hydrogel, which was an imidazole-polyorganophosphazene-hydrogen complex with sustained release of ARSB, significantly diminished fibrotic extracellular matrix components associated with spinal cord injury and improved functional locomotor recovery with an increased number of regenerating axons [ 105 ]. In contrast, chondroitin 6-sulfatase did not influence the extent of axon regeneration.…”

Section: Diseases With Deficiency Of Arylsulfatase Bmentioning

confidence: 99%

Profound Impact of Decline in N-Acetylgalactosamine-4-Sulfatase (Arylsulfatase B) on Molecular Pathophysiology and Human Diseases

Tobacman

Bhattacharyya

2022

IJMS

View full text Add to dashboard Cite

The enzyme N-acetylgalactosamine-4-sulfatase (Arylsulfatase B; ARSB) was originally identified as a lysosomal enzyme which was deficient in Mucopolysaccharidosis VI (MPS VI; Maroteaux-Lamy Syndrome). The newly directed attention to the impact of ARSB in human pathobiology indicates a broader, more pervasive effect, encompassing roles as a tumor suppressor, transcriptional mediator, redox switch, and regulator of intracellular and extracellular-cell signaling. By controlling the degradation of chondroitin 4-sulfate and dermatan sulfate by removal or failure to remove the 4-sulfate residue at the non-reducing end of the sulfated glycosaminoglycan chain, ARSB modifies the binding or release of critical molecules into the cell milieu. These molecules, such as galectin-3 and SHP-2, in turn, influence crucial cellular processes and events which determine cell fate. Identification of ARSB at the cell membrane and in the nucleus expands perception of the potential impact of decline in ARSB activity. The regulation of availability of sulfate from chondroitin 4-sulfate and dermatan sulfate may also affect sulfate assimilation and production of vital molecules, including glutathione and cysteine. Increased attention to ARSB in mammalian cells may help to integrate and deepen our understanding of diverse biological phenomenon and to approach human diseases with new insights.

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“…This product would be an off-the-shelf, pre-packaged and sterilized medical device to promote aligned tissue regeneration and thus restore function. Indeed, the Neuro-Spinal ([ 10 ], ClinicalTrials.gov NCT03762655) and NeuroRegen ([ 11 , 12 , 13 , 14 , 15 ], ClinicalTrials.gov NCT02510365) scaffolds currently in clinical trials are the first generation of such products. However, as their preclinical development began more than a decade ago, recent research themes were not incorporated as part of their design.…”

Section: Discussionmentioning

confidence: 99%

“…However, as their preclinical development began more than a decade ago, recent research themes were not incorporated as part of their design. Recent research themes include conductive hydrogels [ 33 ], hydrogels designed to improve the survival of transplanted stem cells [ 10 ], and hydrogels designed to modify the fibrotic microenvironment [ 11 ]. In contrast, this study is concerned with the mechanical optimisation of the hydrogel component, and importantly, combining with an aligned electrospun nonwoven for directional cues.…”

Section: Discussionmentioning

confidence: 99%

“…This response is a hugely complex series of events that continuously alters over time and is influenced by injury severity. This has been well detailed elsewhere [ 7 , 8 , 9 ] and its modification is the focus of some research groups through transplantation of stem cells [ 10 ] and enzymes [ 11 ], but in short represents a catastrophic scattering of cell debris, breach of the blood-spinal cord barrier, oedema, ischemia, multiple immune-mediated responses and, ultimately, development of the characteristic spinal injury scar. It is the loss of native structure from initial injury and subsequent reorganisation of cells and ECM to form the spinal injury scar that causes loss of function.…”

Section: Introductionmentioning

confidence: 99%

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A Biomimetic Nonwoven-Reinforced Hydrogel for Spinal Cord Injury Repair

et al. 2022

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In clinical trials, new scaffolds for regeneration after spinal cord injury (SCI) should reflect the importance of a mechanically optimised, hydrated environment. Composite scaffolds of nonwovens, self-assembling peptides (SAPs) and hydrogels offer the ability to mimic native spinal cord tissue, promote aligned tissue regeneration and tailor mechanical properties. This work studies the effects of an aligned electrospun nonwoven of P11-8—enriched poly(ε-caprolactone) (PCL) fibres, integrated with a photo-crosslinked hydrogel of glycidylmethacrylated collagen (collagen-GMA), on neurite extension. Mechanical properties of collagen-GMA hydrogel in compression and shear were recorded, along with cell viability. Collagen-GMA hydrogels showed J-shaped stress–strain curves in compression, mimicking native spinal cord tissue. For hydrogels prepared with a 0.8-1.1 wt.% collagen-GMA concentration, strain at break values were 68 ± 1–81 ± 1% (±SE); maximum stress values were 128 ± 9–311 ± 18 kPa (±SE); and maximum force values were 1.0 ± 0.1–2.5 ± 0.1 N (±SE). These values closely mimicked the compression values for feline and porcine tissue in the literature, especially those for 0.8 wt.%. Complex shear modulus values fell in the range 345–2588 Pa, with the lower modulus hydrogels in the range optimal for neural cell survival and growth. Collagen-GMA hydrogel provided an environment for homogenous and three-dimensional cell encapsulation, and high cell viability of 84 ± 2%. Combination of the aligned PCL/P11-8 electrospun nonwoven and collagen-GMA hydrogel retained fibre alignment and pore structure, respectively, and promoted aligned neurite extension of PC12 cells. Thus, it is possible to conclude that scaffolds with mechanical properties that both closely mimic native spinal cord tissue and are optimal for neural cells can be produced, which also promote aligned tissue regeneration when the benefits of hydrogels and electrospun nonwovens are combined.

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Dual-functional hydrogel system for spinal cord regeneration with sustained release of arylsulfatase B alleviates fibrotic microenvironment and promotes axonal regeneration

Cited by 29 publications

References 67 publications

Profound Impact of Decline in N-Acetylgalactosamine-4-Sulfatase (Arylsulfatase B) on Molecular Pathophysiology and Human Diseases

Profound Impact of Decline in N-Acetylgalactosamine-4-Sulfatase (Arylsulfatase B) on Molecular Pathophysiology and Human Diseases

Profound Impact of Decline in N-Acetylgalactosamine-4-Sulfatase (Arylsulfatase B) on Molecular Pathophysiology and Human Diseases

A Biomimetic Nonwoven-Reinforced Hydrogel for Spinal Cord Injury Repair

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