Use of a supramolecular polymeric hydrogel as an effective post-operative pericardial adhesion barrier

Stapleton, Lyndsay M.; Steele, Amanda N.; Wang, Hanjay; Hernandez, Hector Lopez; Yu, Anthony C.; Paulsen, Michael J.; Smith, Anders; Roth, Gillie A.; Thakore, Akshara D.; Lucian, Haley J.; Totherow, Kailey P; Baker, Sam W.; Tada, Yuko; Farry, Justin M.; Eskandari, Anahita; Hironaka, Camille E.; Jaatinen, Kevin J; Williams, Kiah M; Bergamasco, Hunter; Marschel, Clifton; Chadwick, Blaine; Grady, Frederick; Ma, Michael; Appel, Eric A.; Woo, Y. Joseph

doi:10.1038/s41551-019-0442-z

Cited by 177 publications

(208 citation statements)

References 48 publications

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“…Adult male rats (n = 6, 8-10 weeks old, 270-330 g) underwent permanent ligation of the LAD coronary artery as previously described [17,19,32]. The animals were anesthetized using 2-3% inhaled isoflurane (Fluriso, VetOne, Boise, ID, USA) delivered at 1 L/min, and then endotracheally intubated with a 16 G angiocatheter.…”

Section: Adult Rat Myocardial Infarction Modelmentioning

confidence: 99%

Natural Heart Regeneration in a Neonatal Rat Myocardial Infarction Model

Wang

Paulsen

Hironaka

et al. 2020

Cells

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Newborn mice and piglets exhibit natural heart regeneration after myocardial infarction (MI). Discovering other mammals with this ability would provide evidence that neonatal cardiac regeneration after MI may be a conserved phenotype, which if activated in adults could open new options for treating ischemic cardiomyopathy in humans. Here, we hypothesized that newborn rats undergo natural heart regeneration after MI. Using a neonatal rat MI model, we performed left anterior descending coronary artery ligation or sham surgery in one-day-old rats under hypothermic circulatory arrest (n = 74). Operative survival was 97.3%. At 1 day post-surgery, rats in the MI group exhibited significantly reduced ejection fraction (EF) compared to shams (87.1% vs. 53.0%, p < 0.0001). At 3 weeks post-surgery, rats in the sham and MI groups demonstrated no difference in EF (71.1% vs. 69.2%, respectively, p = 0.2511), left ventricular wall thickness (p = 0.9458), or chamber diameter (p = 0.7801). Masson’s trichome and picrosirius red staining revealed minimal collagen scar after MI. Increased numbers of cardiomyocytes positive for 5-ethynyl-2′-deoxyuridine (p = 0.0072), Ki-67 (p = 0.0340), and aurora B kinase (p = 0.0430) were observed within the peri-infarct region after MI, indicating ischemia-induced cardiomyocyte proliferation. Overall, we present a neonatal rat MI model and demonstrate that newborn rats are capable of endogenous neocardiomyogenesis after MI.

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Section: Adult Rat Myocardial Infarction Modelmentioning

confidence: 99%

Natural Heart Regeneration in a Neonatal Rat Myocardial Infarction Model

Wang

Paulsen

Hironaka

et al. 2020

Cells

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“…Beyond the use of core-shell NPs as a stand alone delivery vector, they have recently been exploited as building blocks in the assembly of shear-thinning and selfhealing, polymer-nanoparticle (PNP) hydrogels for site specific delivery following local injection (Appel et al, 2015b). PNP hydrogels have also been used as nanocarrier bioinks for additive manufacturing, as a sprayable barrier to prevent tissue adhesion following cardiothoracic surgery, and as a depot for the local release of cytokines and recruitment of immune cells (Fenton et al, 2019;Guzzi et al, 2019;Lopez Hernandez et al, 2019;Stapleton et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Automated and Continuous Production of Polymeric Nanoparticles

Bovone

Steiner

Guzzi

et al. 2019

Front. Bioeng. Biotechnol.

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Polymeric nanoparticles (NPs) are increasingly used as therapeutics, diagnostics, and building blocks in (bio)materials science. Current barriers to translation are limited control over NP physicochemical properties and robust scale-up of their production. Flow-based devices have emerged for controlled production of polymeric NPs, both for rapid formulation screening (∼µg min −1) and on-scale production (∼mg min −1). While flow-based devices have improved NP production compared to traditional batch processes, automated processes are desired for robust NP production at scale. Therefore, we engineered an automated coaxial jet mixer (CJM), which controlled the mixing of an organic stream containing block copolymer and an aqueous stream, for the continuous nanoprecipitation of polymeric NPs. The CJM was operated stably under computer control for up to 24 h and automated control over the flow conditions tuned poly(ethylene glycol)-block-polylactide (PEG 5K-b-PLA 20K) NP size between ≈56 nm and ≈79 nm. In addition, the automated CJM enabled production of NPs of similar size (D h ≈ 50 nm) from chemically diverse block copolymers, PEG 5K-b-PLA 20K , PEG-block-poly(lactide-co-glycolide) (PEG 5K-b-PLGA 20K), and PEG-block-polycaprolactone (PEG 5K-b-PCL 20K), by tuning the flow conditions for each block copolymer. Further, the automated CJM was used to produce model nanotherapeutics in a reproducible manner without user intervention. Finally, NPs produced with the automated CJM were used to scale the formation of injectable polymer-nanoparticle (PNP) hydrogels, without modifying the mechanical properties of the PNP gel. In conclusion, the automated CJM enabled stable, tunable, and continuous production of polymeric NPs, which are needed for the scale-up and translation of this important class of biomaterials.

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“…However, 3 traditional covalently cross-linked hydrogels are often not appropriate for vaccine applications as they cannot be easily administered and have limitations in their delivery kinetics for diverse cargo 24 . Polymer-nanoparticle (PNP) hydrogels are a type of supramolecular hydrogel where the polymeric constituents are held together by dynamic, multivalent non-covalent interactions between polymers and nanoparticles [25][26][27][28] . These materials exhibit many favorable characteristics such as high drug loading capacity, gentle conditions for encapsulation of biologic cargo, sustained delivery of cargo, and mechanical tunability 24,28,29 .…”

Section: Main Articlementioning

confidence: 99%

“…These materials exhibit many favorable characteristics such as high drug loading capacity, gentle conditions for encapsulation of biologic cargo, sustained delivery of cargo, and mechanical tunability 24,28,29 . In addition, PNP hydrogels are easily administered due to their shear thinning and self-healing properties 27,30,31 . The fabrication process, which is easily scaled and therefore highly translatable, involves straightforward mixing of the polymer, nanoparticles (NPs), and an aqueous solution of cargo 28,32 .…”

Section: Main Articlementioning

confidence: 99%

Injectable hydrogels for sustained co-delivery of subunit vaccines enhance humoral immunity

Roth¹,

Gale

Alcántara‐Hernández

et al. 2020

Preprint

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Vaccines aim to elicit a robust, yet targeted, immune response. Failure of a vaccine to elicit such a response arises in part from inappropriate temporal control over antigen and adjuvant presentation to the immune system. In this work, we sought to exploit the immune system's natural response to extended pathogen exposure during infection by designing an easily administered slow-delivery vaccine platform. We utilized an injectable and self-healing polymernanoparticle (PNP) hydrogel platform to prolong the co-delivery of vaccine components to the immune system. We demonstrated that these hydrogels exhibit unique delivery characteristics whereby physicochemically distinct compounds (such as antigen and adjuvant) could be codelivered over the course of weeks. When administered in mice, hydrogel-based sustained vaccine exposure enhanced the magnitude, duration, and quality of the humoral immune response compared to standard PBS bolus administration of the same model vaccine. We report that the creation of a local inflammatory niche within the hydrogel, coupled with sustained release of vaccine cargo, enhanced the magnitude and duration of germinal center responses in the lymph nodes. This strengthened germinal center response promoted greater antibody affinity maturation, resulting in a more than 1000-fold increase in antigen-specific antibody affinity in comparison to bolus immunization. Furthermore, our technology improved the efficacy of an influenza hemagglutinin subunit vaccine compared to the most potent adjuvant system used clinically for influenza vaccination, by increasing antibody titers and cross-reactivity against other hemagglutinin variants. In summary, this work introduces a simple and effective vaccine delivery platform that increases the potency and durability of subunit vaccines.

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Use of a supramolecular polymeric hydrogel as an effective post-operative pericardial adhesion barrier

Cited by 177 publications

References 48 publications

Natural Heart Regeneration in a Neonatal Rat Myocardial Infarction Model

Natural Heart Regeneration in a Neonatal Rat Myocardial Infarction Model

Automated and Continuous Production of Polymeric Nanoparticles

Injectable hydrogels for sustained co-delivery of subunit vaccines enhance humoral immunity

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