Tailoring the degradation rates of thermally responsive hydrogels designed for soft tissue injection by varying the autocatalytic potential

Zhu, Yang; Jiang, Hongbin; Ye, Sang‐Ho; Yoshizumi, Tomo; Wagner, William R.

doi:10.1016/j.biomaterials.2015.02.100

Cited by 42 publications

(32 citation statements)

References 56 publications

(50 reference statements)

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“…At 3 d, 1 w and 2 w after MI, hydrogel that was fluorescently labeled by the incorporation of a green fluorescent monomer during polymer synthesis was injected into the infarction zone and rats were sacrificed within 30 min after the injections [24]. As shown in the tissue sections of Figure 5, the injected hydrogel formed distinct volumes in the LV wall.…”

Section: Resultsmentioning

confidence: 99%

Timing effect of intramyocardial hydrogel injection for positively impacting left ventricular remodeling after myocardial infarction

et al. 2016

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Intramyocardial injection of various injectable hydrogel materials has shown benefit in positively impacting the course of left ventricular (LV) remodeling after myocardial infarction (MI). However, since LV remodeling is a complex, time dependent process, the most efficacious time of hydrogel injection is not clear. In this study, we injected a relatively stiff, thermoresponsive and bioabsorbable hydrogel in rat hearts at 3 different time points - immediately after MI (IM), 3 d post-MI (3D), and 2 w post-MI (2W), corresponding to the beginnings of the necrotic, fibrotic and chronic remodeling phases. The employed left anterior descending coronary artery ligation model showed expected infarction responses including functional loss, inflammation and fibrosis with distinct time dependent patterns. Changes in LV geometry and contractile function were followed by longitudinal echocardiography for 10 w post-MI. While all injection times positively affected LV function and wall thickness, the 3D group gave better functional outcomes than the other injection times and also exhibited more local vascularization and less inflammatory markers than the earlier injection time. The results indicate an important role for injection timing in the increasingly explored concept of post-MI biomaterial injection therapy and suggest that for hydrogels with mechanical support as primary function, injection at the beginning of the fibrotic phase may provide improved outcomes.

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Section: Resultsmentioning

confidence: 99%

Timing effect of intramyocardial hydrogel injection for positively impacting left ventricular remodeling after myocardial infarction

et al. 2016

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“…This increase is likely the contribution of VP as PVP is highly hydrophilic. Previous studies have demonstrated that copolymerization of NIPAAm with hydrophilic components like HEMA, acrylic acid, propylacrylic acid, and methacrylic acid can increase thermal transition temperatures of PNIPAAm [48, 50, 51, 68]. …”

Section: Discussionmentioning

confidence: 99%

Thermosensitive, fast gelling, photoluminescent, highly flexible, and degradable hydrogels for stem cell delivery

Niu

et al. 2019

Acta Biomaterialia

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Stem cell therapy is a promising approach to regenerate ischemic cardiovascular tissues yet experiences low efficacy. One of the major causes is inferior cell retention in tissues. Injectable cell carriers that can quickly solidify upon injection into tissues so as to immediately increase viscosity have potential to largely improve cell retention. A family of injectable, fast gelling, and thermosensitive hydrogels were developed for delivering stem cells into heart and skeletal muscle tissues. The hydrogels were also photoluminescent with low photobleaching, allowing for non-invasively tracking hydrogel biodistribution and retention by fluorescent imaging. The hydrogels were polymerized by N-Isopropylacrylamide (NIPAAm), 2-hydroxyethyl methacrylate (HEMA), 1-vinyl-2-pyrrolidinone (VP), and acrylate-oligolactide (AOLA), followed by conjugation with hypericin (HYP). The hydrogel solutions had thermal transition temperatures around room temperature, and were readily injectable at 4°C. The solutions were able to quickly solidify within 7s at 37°C. The formed gels were highly flexible possessing similar moduli as the heart and skeletal muscle tissues. In vitro, hydrogel fluorescence intensity decreased proportionally to weight loss. After being injected into thigh muscles, the hydrogel can be detected by an in vivo imaging system for 4 weeks. The hydrogels showed excellent biocompatibility in vitro and in vivo, and can stimulate mesenchymal stem cell (MSC) proliferation and paracrine effects. The fast gelling hydrogel remarkably increased MSC retention in thigh muscles compared to slow gelling collagen, and non-gelling PBS. These hydrogels have potential to efficiently deliver stem cells into tissues. Hydrogel degradation can be non-invasively and real-time tracked.

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“…The MAPLA was synthesized as previously described [12]. Poly(NIPAAm-co-VP-co-MAPLA) copolymers were synthesized from NIPAAm, VP, and MAPLA by free radical polymerization.…”

Section: Methodsmentioning

confidence: 99%

“…Injection studies in rats were performed as previously described except that the end point was set at 28 days after injection [12]. …”

Section: Methodsmentioning

confidence: 99%

Design of a Coupled Thermoresponsive Hydrogel and Robotic System for Postinfarct Biomaterial Injection Therapy

Zhu

Wood

Fok

et al. 2016

The Annals of Thoracic Surgery

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Background In preclinical testing, ventricular wall injection of hydrogels has been shown to be effective in modulating ventricular remodeling and preserving cardiac function. For some approaches, early-stage clinical trials are under way. The hydrogel delivery method varies, with minimally invasive approaches being preferred. Endocardial injections carry a risk of hydrogel regurgitation into the circulation, and precise injection patterning is a challenge. An epicardial approach with a thermally gelling hydrogel through the subxiphoid pathway overcomes these disadvantages. Methods A relatively stiff, thermally responsive, injectable hydrogel based on N-isopropylacrylamide and N-vinylpyrrolidone (VP gel) was synthesized and characterized. VP gel thermal behavior was tuned to couple with a transepicardial injection robot, incorporating a cooling feature to achieve injectability. Ventricular wall injections of the optimized VP gel have been performed ex vivo and on beating porcine hearts. Results Thermal transition temperature, viscosity, and gelling time for the VP gel were manipulated by altering N-vinylpyrrolidone content. The target parameters for cooling in the robotic system were chosen by thermal modeling to support smooth, repeated injections on an ex vivo heart. Injections at predefined locations and depth were confirmed in an infarcted porcine model. Conclusions A coupled thermoresponsive hydrogel and robotic injection system incorporating a temperature-controlled injectate line was capable of targeted injections and amenable to use with a subxiphoid transepicardial approach for hydrogel injection after myocardial infarction. The confirmation of precise location and depth injections would facilitate a patient-specific planning strategy to optimize injection patterning to maximize the mechanical benefits of hydrogel placement.

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Tailoring the degradation rates of thermally responsive hydrogels designed for soft tissue injection by varying the autocatalytic potential

Cited by 42 publications

References 56 publications

Timing effect of intramyocardial hydrogel injection for positively impacting left ventricular remodeling after myocardial infarction

Timing effect of intramyocardial hydrogel injection for positively impacting left ventricular remodeling after myocardial infarction

Thermosensitive, fast gelling, photoluminescent, highly flexible, and degradable hydrogels for stem cell delivery

Design of a Coupled Thermoresponsive Hydrogel and Robotic System for Postinfarct Biomaterial Injection Therapy

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