Supramolecular hydrogels encapsulating bioengineered mesenchymal stem cells for ischemic therapy

Hwang, Byung Woo; Kim, Young Eun; Kim, Mungu; Han, Seulgi; Bok, Seoyeon; Park, Kyeng Min; Shrinidhi, Annadka; Kim, Ki Su; Ahn, G‐One; Hahn, Sei Kwang

doi:10.1039/c8ra00464a

Cited by 8 publications

(13 citation statements)

References 27 publications

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“…Especially, supramolecular HA hydrogels prepared by mixing diaminohexane-conjugated HA (DAH-HA) and CB[6]-conjugated HA (CB[6]-HA) have been extensively investigated for the delivery of bioengineered stem cells (Figure a). − The hydrogels have been first exploited as a platform scaffold to deliver fibroblasts and mesenchymal stem cells (MSCs) for tissue engineering applications (Figure b). , After demonstrating the feasibility of the hydrogel system as a 3D scaffold, MSCs genetically engineered to secrete therapeutic proteins were entrapped into the hydrogels and applied to treat target diseases. Bioengineered MSCs to produce mutant interleukin-12 (IL-12M) delivered by the CB[6]/DAH-HA hydrogels showed a significant therapeutic effect on treating cancer (Figure c) .…”

Section: Ha-based Medicinesmentioning

confidence: 99%

“…Bioengineered MSCs to produce mutant interleukin-12 (IL-12M) delivered by the CB[6]/DAH-HA hydrogels showed a significant therapeutic effect on treating cancer (Figure c) . Furthermore, MSCs bioengineered to secrete vascular endothelial growth factor A (VEGF-A) and hepatocyte growth factor (HGF) delivered by the CB[6]/DAH-HA hydrogels promoted vascular repair and enhanced blood perfusion in hind-limb ischemia model mice (Figure d) …”

Section: Ha-based Medicinesmentioning

confidence: 99%

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Hyaluronic Acid Derivatives for Translational Medicines

Kim¹,

Shin

Han

et al. 2019

Biomacromolecules

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The recent progress in various biomaterials with unique physiological and pharmacological properties has expedited the development of translational medicines for the diagnosis, prognosis, and therapy of intractable diseases. Hyaluronic acid (HA) is one of such biomaterials that has attracted great attention due to its unique characteristics for biomedical applications. In this Perspective, we provide an overview of HA-based medicines in a variety of forms such as chemical and biological conjugates, nanoparticles, nanoparticle hybrid systems, hydrogels, and nanogels. We highlight the current-state-of-the-art strategies to design and optimize innovative HA-based medicines for their clinical translations. Finally, we discuss the challenges for technical hurdles and the future directions to expand the feasibility of HA-based translational medicines.

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Section: Ha-based Medicinesmentioning

confidence: 99%

Section: Ha-based Medicinesmentioning

confidence: 99%

Hyaluronic Acid Derivatives for Translational Medicines

Kim¹,

Shin

Han

et al. 2019

Biomacromolecules

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“…The result pointed out that the bioactivity of VEGF and HGF still maintained after released from SAPs hydrogel. Additionally, the synergistic angiogenic effect of VEGF and HGF suggested that HGF might enhance endogenous VEGF expression and co-regulate their pathways during endothelial morphogenesis 41, 42.…”

Section: Discussionmentioning

confidence: 99%

Bioinspired Self-assembling Peptide Hydrogel with Proteoglycan-assisted Growth Factor Delivery for Therapeutic Angiogenesis

Huang¹,

Wang²,

Chen³

et al. 2019

Theranostics

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Critical challenges still exist in surgical theaters and emergency rooms to stop bleeding effectively and facilitate wound healing efficiently. In circumstances of tissue ischemia, it is essential to induce proper angiogenesis to provide adequate vascular supply to the injury site.Methods: In view of these clinical unmet needs, we propose an applicable approach by designing functionalized self-assembling peptide (SAP) hydrogel with two sequences of RADA16-GGQQLK (QLK) and RADA16-GGLRKKLGKA (LRK) in this study. The SAP hydrogel conjugated with QLK functional motif could be crosslinked by endogenous transglutaminase, one of the intrinsic factors secreted during the coagulation process, the mechanical property of the hydrogel can then be enhanced without the need of external support. On the other hand, the LRK sequence exhibited a good binding affinity with the proteoglycan heparan sulfate and could act as a cofactor by sustaining the release of embedded growth factors.Results: The results showed that this SAP solution underwent self-assembling process in a physiological environment, formed hydrogel in situ, and possessed good shear thinning property with injectability. After pH adjustment, the SAP developed densely-compacted fiber entanglement that closely mimicked the three-dimensional fibrous framework of natural extracellular matrix. Such scaffold could not only support the survival of encapsulating cells but also promote the capillary-like tubular structure formation by dual angiogenic growth factors. The ex ovo chicken chorioallantoic membrane assay demonstrated that the growth factor-loaded hydrogel promoted the sprout of surrounding vessels in a spoke-wheel pattern compared to growth factor-free counterparts.Conclusion: The designer bioinspired SAP hydrogel may be an attractive and promising therapeutic modality for minimally-invasive surgery, ischemic tissue disorders and chronic wound healing.

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“…To overcome such limitations, Kim's group suggested novel supramolecular hydrogel assemblies based on hyaluronic acid modified with pumpkin‐shaped cucurbit[6]uril (CB[6]) or diaminohexane groups . The highly selective and strong CB[6]–diaminohexane interaction allowed cell encapsulation on self‐assembled hydrogels, which could then be later modularly modified by treating the hydrogel with multifunctional tags‐CB[6], which included RGD domains to promote cell adhesion, FITC probes for in vivo detection, or TGF‐β3 and dexamethasone to regulate mesenchymal stem cells' chondrogenic differentiation . Other interesting systems can comprise dock‐and‐lock (DnL) mechanisms based on engineered proteins and anchoring proteins attached to multiarm crosslinker polymers, which can instantly lock onto recombinant “docking” domains under physiological conditions .…”

Section: Cell–biomaterials Assembliesmentioning

confidence: 99%

Advanced Bottom‐Up Engineering of Living Architectures

et al. 2019

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Bottom‐up tissue engineering is a promising approach for designing modular biomimetic structures that aim to recapitulate the intricate hierarchy and biofunctionality of native human tissues. In recent years, this field has seen exciting progress driven by an increasing knowledge of biological systems and their rational deconstruction into key core components. Relevant advances in the bottom‐up assembly of unitary living blocks toward the creation of higher order bioarchitectures based on multicellular‐rich structures or multicomponent cell–biomaterial synergies are described. An up‐to‐date critical overview of long‐term existing and rapidly emerging technologies for integrative bottom‐up tissue engineering is provided, including discussion of their practical challenges and required advances. It is envisioned that a combination of cell–biomaterial constructs with bioadaptable features and biospecific 3D designs will contribute to the development of more robust and functional humanized tissues for therapies and disease models, as well as tools for fundamental biological studies.

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Supramolecular hydrogels encapsulating bioengineered mesenchymal stem cells for ischemic therapy

Cited by 8 publications

References 27 publications

Hyaluronic Acid Derivatives for Translational Medicines

Hyaluronic Acid Derivatives for Translational Medicines

Bioinspired Self-assembling Peptide Hydrogel with Proteoglycan-assisted Growth Factor Delivery for Therapeutic Angiogenesis

Advanced Bottom‐Up Engineering of Living Architectures

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