A peptide-modified chitosan–collagen hydrogel for cardiac cell culture and delivery

Reis, Lewis A.; Chiu, Loraine L. Y.; Liang, Yan; Hyunh, Kent; Momen, Abdul; Radišić, Milica

doi:10.1016/j.actbio.2011.11.030

Cited by 144 publications

(121 citation statements)

References 63 publications

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Section: Clinical Perspective On P 341mentioning

confidence: 98%

“…12 Briefly, 2.5-mg/mL 1:1 (mass:mass) chitosan-collagen hydrogel was prepared to produce control (no peptide) or QHG213H hydrogel (651±8 nmol peptide/mL gel) and kept on ice for ≤3 hours before use.…”

Section: Peptide-modified Chitosan-collagen Hydrogel (Qhg213h)mentioning

confidence: 99%

“…12 Treatments were randomized among the animals and the surgeon was blinded to the treatment given. Injections were performed using a 28-guage needle (BD Biosciences) inserted into the peri-infarct left ventricle (LV) wall and directed toward the developing scar (MI zone).…”

Section: Experimental Groups and Injection Timelinementioning

confidence: 99%

“…[22][23][24][25][26] In our previous study using the QHREDGS-modified chitosan-collagen hydrogel, we demonstrated increased cardiomyocyte survival in in vitro culture and negligible hydrogel degradation therein, as well as in vivo biocompatibility in a subcutaneous model. 12 This indicates that peptide release, which depends on hydrogel degradation, was not required for improved cardiomyocyte survival.Based on these findings, we sought to investigate the effect of our QHREDGS-modified chitosan-collagen hydrogel in vivo after MI. We examined the in vivo biodistribution, localization, and lifespan of the hydrogel in the heart, and its effect on cardiac remodeling in a rat acute MI model at 6 weeks, when pathological remodeling is considered to be complete.…”

mentioning

confidence: 98%

“…EDC is a zero-length cross-linker; therefore, no other chemical moieties aside from the QHREDGS peptide are added to chitosan. The hydrogel is made by mixing collagen and the QHREDGS-chitosan without the addition of any exogenous chemical cross-linkers to facilitate gelation and without formation of permanent crosslinks between chitosan and collagen.The peptide was immobilized onto chitosan by covalent cross-linking because as an integrin-binding ligand, QHREDGS does not need to be internalized to function, 12 and immobilization has been demonstrated, in previous studies, to both reduce the amount of bioactive molecules required and prolong signaling by stabilizing the receptor/ligand complex. [22][23][24][25][26] In our previous study using the QHREDGS-modified chitosan-collagen hydrogel, we demonstrated increased cardiomyocyte survival in in vitro culture and negligible hydrogel degradation therein, as well as in vivo biocompatibility in a subcutaneous model.…”

mentioning

confidence: 99%

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Hydrogels With Integrin-Binding Angiopoietin-1–Derived Peptide, QHREDGS, for Treatment of Acute Myocardial Infarction

Reis

Chiu

et al. 2015

Circ: Heart Failure

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Chitosan and collagen are natural, biodegradable, and biocompatible polymers that have been explored for their potential use in the treatment of cardiac dysfunction. [4][5][6][7][8][9] Typically, collagen and chitosan, alone or in combination, are crosslinked using exogenous, sometimes toxic, chemical crosslinkers to improve the hydrogel mechanical properties. 4,10,11 However, we have previously shown that chitosan-collagen composites gel because of ionic interactions at physiological temperature and pH to form mechanically stable hydrogels that are appropriate for in vivo application.12 Furthermore, the collagen-chitosan interaction within the gels resembles the collagen-glycosaminoglycan interaction found in vivo in the extracellular matrix. 13 Thus, chitosan-collagen may mediate physiological cell-matrix interactions.The functional success of hydrogel-based cardiac and cell therapies can be improved by modifying biomaterials with bioactive molecules because bioactive molecules (cytokines, Original Article© 2015 American Heart Association, Inc.Circ Heart Fail is available at http://circheartfailure.ahajournals.org DOI: 10.1161/CIRCHEARTFAILURE.114.001881Background-Hydrogels are being actively investigated for direct delivery of cells or bioactive molecules to the heart after myocardial infarction (MI) to prevent cardiac functional loss. We postulate that immobilization of the prosurvival angiopoietin-1-derived peptide, QHREDGS, to a chitosan-collagen hydrogel could produce a clinically translatable thermoresponsive hydrogel to attenuate post-MI cardiac remodeling. Methods and Results-In a rat MI model, QHREDGS-conjugated hydrogel (QHG213H), control gel, or PBS was injected into the peri-infarct/MI zone. By in vivo tracking and chitosan staining, the hydrogel was demonstrated to remain in situ for 2 weeks and was cleared in ≈3 weeks. By echocardiography and pressure-volume analysis, the QHG213H hydrogel significantly improved cardiac function compared with the controls. Scar thickness and scar area fraction were also significantly improved with QHG213H gel injection compared with the controls. There were significantly more cardiomyocytes, determined by cardiac troponin-T staining, in the MI zone of the QHG213H hydrogel group; and hydrogel injection did not induce a significant inflammatory response as assessed by polymerase chain reaction and an inflammatory cytokine assay. The interaction of cardiomyocytes and cardiac fibroblasts with QHREDGS was found to be mediated by β 1 -integrins. Conclusions-We demonstrated for the first time that the QHG213H peptide-modified hydrogel can be injected in the beating heart where it remains localized for a clinically effective period. Moreover, the QHG213H hydrogel induced significant cardiac functional and morphological improvements after MI relative to the controls. and activates prosurvival pathways. 20 We identified the short sequence QHREDGS as the integrin-binding motif of Ang1, and the QHREDGS peptide was found to support cardiomyocyte attachment and survival simila...

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Section: Clinical Perspective On P 341mentioning

confidence: 98%

Section: Peptide-modified Chitosan-collagen Hydrogel (Qhg213h)mentioning

confidence: 99%

Section: Experimental Groups and Injection Timelinementioning

confidence: 99%

mentioning

confidence: 98%

mentioning

confidence: 99%

See 3 more Smart Citations

Hydrogels With Integrin-Binding Angiopoietin-1–Derived Peptide, QHREDGS, for Treatment of Acute Myocardial Infarction

Reis

Chiu

et al. 2015

Circ: Heart Failure

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Bioinspired Reversibly Cross‐linked Hydrogels Comprising Polypeptide Micelles Exhibit Enhanced Mechanical Properties

Ghoorchian

Simon

Bharti

et al. 2015

Adv Funct Materials

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Noncovalently cross-linked networks are attractive hydrogel platforms because of their facile fabrication, dynamic behavior, and biocompatibility. The majority of noncovalently cross-linked hydrogels, however, exhibits poor mechanical properties, which signifi cantly limit their utility in load bearing applications. To address this limitation, hydrogels are presented composed of micelles created from genetically engineered, amphiphilic, elastin-like polypeptides that contain a relatively large hydrophobic block and a hydrophilic terminus that can be cross-linked through metal ion coordination. To create the hydrogels, heat is fi rstly used to trigger the self-assembly of the polypeptides into monodisperse micelles that display transition metal coordination motifs on their coronae, and subsequently cross-link the micelles by adding zinc ions. These hydrogels exhibit hierarchical structure, are stable over a large temperature range, and exhibit tunable stiffness, self-healing, and fatigue resistance. Gels with polypeptide concentration of 10%, w/v, and higher show storage moduli of ≈1 MPa from frequency sweep tests and exhibit self-healing within minutes. These reversibly cross-linked, hierarchical hydrogels with enhanced mechanical properties have potential utility in a variety of biomedical applications.

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Injectable Chitosan‐Based Scaffolds in Regenerative Medicine and their Clinical Translatability

Mekhail¹,

Tabrizian²

2014

Adv Healthcare Materials

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Injectable scaffolds (IS) are polymeric solutions that are injected in vivo and undergo gelation in response to physiological or non-physiological stimuli. Interest in using IS in regenerative medicine has been increasing this past decade. IS are administered in vivo using minimally invasive surgery, which reduces hospitalization time and risk of surgical wound infection. Here, chitosan is explored as an excellent candidate for developing IS. A literature search reveals that 27% of IS publications in the past decade investigated injectable chitosan scaffolds (ICS). This increasing interest in chitosan stems from its many desirable physicochemical properties. The first section of this Progress Report is a comprehensive study of all physical, chemical, and biological stimuli that have been explored to induce ICS gelation in vivo. Second, the use of ICS is investigated in four major regenerative medicine applications, namely bone, cartilage, cardiovascular, and neural regeneration. Finally, an overall critique of the ICS literature in light of clinical translatability is presented. Even though ICS have been widely explored in the literature, very few have progressed to clinical trials. The authors discuss the current barriers to moving ICS into the clinic and provide suggestions regarding what is needed to overcome those challenges.

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A peptide-modified chitosan–collagen hydrogel for cardiac cell culture and delivery

Cited by 144 publications

References 63 publications

Hydrogels With Integrin-Binding Angiopoietin-1–Derived Peptide, QHREDGS, for Treatment of Acute Myocardial Infarction

Hydrogels With Integrin-Binding Angiopoietin-1–Derived Peptide, QHREDGS, for Treatment of Acute Myocardial Infarction

Bioinspired Reversibly Cross‐linked Hydrogels Comprising Polypeptide Micelles Exhibit Enhanced Mechanical Properties

Injectable Chitosan‐Based Scaffolds in Regenerative Medicine and their Clinical Translatability

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