Efficient protein incorporation and release by a jigsaw-shaped self-assembling peptide hydrogel for injured brain regeneration

AbstractDuring injured tissue regeneration, the extracellular matrix plays a key role in controlling and coordinating various cellular events by binding and releasing secreted proteins in addition to promoting cell adhesion. Herein, we develop a cell-adhesive fiber-forming peptide that mimics the jigsaw-shaped hydrophobic surface in the dovetail-packing motif of glycophorin A as an artificial extracellular matrix for regenerative therapy. We show that the jigsaw-shaped self-assembling peptide forms several-micrometer-long supramolecular nanofibers through a helix-to-strand transition to afford a hydrogel under physiological conditions and disperses homogeneously in the hydrogel. The molecular- and macro-scale supramolecular properties of the jigsaw-shaped self-assembling peptide hydrogel allow efficient incorporation and sustained release of vascular endothelial growth factor, and demonstrate cell transplantation-free regenerative therapeutic effects in a subacute-chronic phase mouse stroke model. This research highlights a therapeutic strategy for injured tissue regeneration using the jigsaw-shaped self-assembling peptide supramolecular hydrogel.

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Self-assembling peptide hydrogel fosters chondrocyte extracellular matrix production and cell division: Implications for cartilage tissue repair

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.142309999 ◽

2002 ◽

Vol 99 (15) ◽

pp. 9996-10001 ◽

Cited By ~ 761

Author(s):

J. Kisiday ◽

M. Jin ◽

B. Kurz ◽

H. Hung ◽

C. Semino ◽

...

Keyword(s):

Extracellular Matrix ◽

Cell Division ◽

Tissue Repair ◽

Cartilage Tissue ◽

Self Assembling ◽

Extracellular Matrix Production ◽

Matrix Production ◽

Peptide Hydrogel

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Faculty Opinions recommendation of Tissue regeneration of the vocal fold using bone marrow mesenchymal stem cells and synthetic extracellular matrix injections in rats.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.2889961.2558060 ◽

2010 ◽

Author(s):

Ravindhra G Elluru

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Extracellular Matrix ◽

Mesenchymal Stem Cells ◽

Tissue Regeneration ◽

Vocal Fold ◽

Marrow Mesenchymal Stem Cells

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Therapeutic Effects of the Addition of Fibroblast Growth Factor-2 to Biodegradable Gelatin/Magnesium-Doped Calcium Silicate Hybrid 3D-Printed Scaffold with Enhanced Osteogenic Capabilities for Critical Bone Defect Restoration

Biomedicines ◽

10.3390/biomedicines9070712 ◽

2021 ◽

Vol 9 (7) ◽

pp. 712

Author(s):

Wei-Yun Lai ◽

Yen-Jen Chen ◽

Alvin Kai-Xing Lee ◽

Yen-Hong Lin ◽

Yu-Wei Liu ◽

...

Keyword(s):

Growth Factor ◽

Fibroblast Growth Factor ◽

Bone Tissue ◽

Tissue Regeneration ◽

Calcium Silicate ◽

Clinical Applications ◽

Fibroblast Growth Factor 2 ◽

Therapeutic Effects ◽

Fibroblast Growth ◽

3D Printed

Worldwide, the number of bone fractures due to traumatic and accidental injuries is increasing exponentially. In fact, repairing critical large bone defects remains challenging due to a high risk of delayed union or even nonunion. Among the many bioceramics available for clinical use, calcium silicate-based (CS) bioceramics have gained popularity due to their good bioactivity and ability to stimulate cell behavior. In order to improve the shortcomings of 3D-printed ceramic scaffolds, which do not easily carry growth factors and do not provide good tissue regeneration effects, the aim of this study was to use a gelatin-coated 3D-printed magnesium-doped calcium silicate (MgCS) scaffold with genipin cross-linking for regulating degradation, improving mechanical properties, and enhancing osteogenesis behavior. In addition, we consider the effects of fibroblast growth factor-2 (FGF-2) loaded into an MgCS scaffold with and without gelatin coating. Furthermore, we cultured the human Wharton jelly-derived mesenchymal stem cells (WJMSC) on the scaffolds and observed the biocompatibility, alkaline phosphatase activity, and osteogenic-related markers. Finally, the in vivo performance was assessed using micro-CT and histological data that revealed that the hybrid bioscaffolds were able to further achieve more effective bone tissue regeneration than has been the case in the past. The above results demonstrated that this type of processing had great potential for future clinical applications and studies and can be used as a potential alternative for future bone tissue engineering research, as well as having good potential for clinical applications.

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Extracellular matrix‐based scaffolding technologies for periodontal and peri‐implant soft tissue regeneration

Journal of Periodontology ◽

10.1002/jper.19-0351 ◽

2019 ◽

Vol 91 (1) ◽

pp. 17-25 ◽

Cited By ~ 13

Author(s):

Lorenzo Tavelli ◽

Michael K. McGuire ◽

Giovanni Zucchelli ◽

Giulio Rasperini ◽

Stephen E. Feinberg ◽

...

Keyword(s):

Extracellular Matrix ◽

Soft Tissue ◽

Tissue Regeneration ◽

Soft Tissue Regeneration

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Stem Cell-Engineered Nanovesicles Exert Proangiogenic and Neuroprotective Effects

Materials ◽

10.3390/ma14051078 ◽

2021 ◽

Vol 14 (5) ◽

pp. 1078

Author(s):

Han Young Kim ◽

Suk Ho Bhang

Keyword(s):

Stem Cells ◽

Endothelial Cells ◽

Mesenchymal Stem Cells ◽

Tissue Regeneration ◽

Therapeutic Agent ◽

Therapeutic Effects ◽

Hydrodynamic Size ◽

Regeneration Strategy ◽

Neuroprotective Effects ◽

The Poor

As a tissue regeneration strategy, the utilization of mesenchymal stem cells (MSCs) has drawn considerable attention. Comprehensive research using MSCs has led to significant preclinical or clinical outcomes; however, improving the survival rate, engraftment efficacy, and immunogenicity of implanted MSCs remains challenging. Although MSC-derived exosomes were recently introduced and reported to have great potential to replace conventional MSC-based therapeutics, the poor production yield and heterogeneity of exosomes are critical hurdles for their further applications. Herein, we report the fabrication of exosome-mimetic MSC-engineered nanovesicles (MSC-NVs) by subjecting cells to serial extrusion through filters. The fabricated MSC-NVs exhibit a hydrodynamic size of ~120 nm, which is considerably smaller than the size of MSCs (~30 μm). MSC-NVs contain both MSC markers and exosome markers. Importantly, various therapeutic growth factors originating from parent MSCs are encapsulated in the MSC-NVs. The MSC-NVs exerted various therapeutic effects comparable to those of MSCs. They also significantly induced the angiogenesis of endothelial cells and showed neuroprotective effects in damaged neuronal cells. The results collectively demonstrate that the fabricated MSC-NVs can serve as a nanosized therapeutic agent for tissue regeneration.

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