Injectable polyisocyanide hydrogel as healing supplement for connective tissue regeneration in an abdominal wound model

Gudde, Aksel N.; van Velthoven, Melissa J.J.; Kouwer, Paul H.J.; Roovers, Jan-Paul W.R.; Guler, Zeliha

doi:10.1016/j.biomaterials.2023.122337

Cited by 10 publications

(9 citation statements)

References 74 publications

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“…The results suggest that the PIC hydrogel is stable and does not degrade at the time scale of the experiments considered in this work. We add that this conclusion is in line with the results obtained from PIC in vivo experiments. ,, …”

Section: Resultssupporting

confidence: 90%

“…We add that this conclusion is in line with the results obtained from PIC in vivo experiments. 21,22,40 PASA was obtained by copolymerizing sodium diphenylamine-4-sulfonate with aniline in an aqueous HCl solution using APS as the oxidizing agent (Figure 1B). The acidic environment ensures the formation of the conductive emeraldine salt form of PASA.…”

Section: Fusion Indexmentioning

confidence: 99%

“…We use hydrogels based on polyisocyanides (PICs), which form a relatively new class of tunable soft materials . By tailoring the molecular weight and polymer concentration, the mechanical properties and network architecture can be controlled for native tissue. , As a result, the material has been successfully applied as a matrix material for 3D in vitro studies to study single cell , and organoid behavior. , Additional in vivo experiments indicate that PIC hydrogels are nontoxic and biocompatible. , In these applications, PIC is biofunctionalized with the commonly used cell-adhesive peptide Gly-Arg-Gly-Asp-Ser (RGD) that allows cell–matrix interactions via integrin binding, but other biological cues can be inserted similarly . These and many other studies demonstrate the capacity of PIC gels to combine a high degree of tunability and similar mechanical properties as native tissue, which makes them particularly suitable for in vitro studies and different tissue engineering purposes.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Conductive Polyisocyanide Hydrogels Inhibit Fibrosis and Promote Myogenesis

Kumari,

Paul,

Verdellen

et al. 2024

ACS Appl. Bio Mater.

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Reliable in vitro models closely resembling native tissue are urgently needed for disease modeling and drug screening applications. Recently, conductive biomaterials have received increasing attention in the development of in vitro models as they permit exogenous electrical signals to guide cells toward a desired cellular response. Interestingly, they have demonstrated that they promote cellular proliferation and adhesion even without external electrical stimulation. This paper describes the development of a conductive, fully synthetic hydrogel based on hybrids of the peptide-modified polyisocyanide (PIC-RGD) and the relatively conductive poly(aniline-co-N-(4-sulfophenyl)aniline) (PASA) and its suitability as the in vitro matrix. We demonstrate that incorporating PASA enhances the PIC-RGD hydrogel’s electroactive nature without significantly altering the fibrous architecture and nonlinear mechanics of the PIC-RGD network. The biocompatibility of our model was assessed through phenotyping cultured human foreskin fibroblasts (HFF) and murine C2C12 myoblasts. Immunofluorescence analysis revealed that PIC–PASA hydrogels inhibit the fibrotic behavior of HFFs while promoting myogenesis in C2C12 cells without electrical stimulation. The composite PIC–PASA hydrogel can actively change the cell fate of different cell types, providing an attractive tool to improve skin and muscle repair.

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Section: Resultssupporting

confidence: 90%

Section: Fusion Indexmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Conductive Polyisocyanide Hydrogels Inhibit Fibrosis and Promote Myogenesis

Kumari,

Paul,

Verdellen

et al. 2024

ACS Appl. Bio Mater.

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“…Notably, the structure and mechanical properties of PIC hydrogels closely resemble collagen and fibrin, , showing fibrous network and strain-stiffening nonlinear mechanics, i.e., gel stiffness increases with the increase of stress (Figure b,c). Because of these highly biomimetic characteristics, previous studies have demonstrated that PIC hydrogels can respond to cell tractions to form bidirectional cell–matrix interactions and facilitate connective tissue regeneration in an abdominal wound model and stay adherent to the wound without additional support. , To endow it with advances of the NIR responsive property, we fabricate a hydrogel composite based on PIC and ETTC conjugated polymer nanoparticles. As illustrated in Scheme a, ETTC NPs were prepared by nanoprecipitation together with amphiphilic polymer (DSPE-PEG-2000) and exhibit a broad NIR absorption spectrum with a prominent shoulder at 808 nm (Figure S1).…”

mentioning

confidence: 99%

Microenvironment with NIR-Controlled ROS and Mechanical Tensions for Manipulating Cell Activities in Wound Healing

Sun,

Jin,

Bao

et al. 2024

Nano Lett.

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The extracellular matrix (ECM) orchestrates cell behavior and tissue regeneration by modulating biochemical and mechanical signals. Manipulating cell–material interactions is crucial for leveraging biomaterials to regulate cell functions. Yet, integrating multiple cues in a single material remains a challenge. Here, near-infrared (NIR)-controlled multifunctional hydrogel platforms, named PIC/CM@NPs, are introduced to dictate fibroblast behavior during wound healing by tuning the matrix oxidative stress and mechanical tensions. PIC/CM@NPs are prepared through cell adhesion-medicated assembly of collagen-like polyisocyanide (PIC) polymers and cell-membrane-coated conjugated polymer nanoparticles (CM@NPs), which closely mimic the fibrous structure and nonlinear mechanics of ECM. Upon NIR stimulation, PIC/CM@NPs composites enhance fibroblast cell proliferation, migration, cytokine production, and myofibroblast activation, crucial for wound closure. Moreover, they exhibit effective and toxin removal antibacterial properties, reducing inflammation. This multifunctional approach accelerates healing by 95%, highlighting the importance of integrating biochemical and biophysical cues in the biomaterial design for advanced tissue regeneration.

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“…Triethylene glycol PICs (PIC3eg), for instance, are an ideal means for wound dressings in mice and rabbits given the fact that the hydrogel’s mechanical properties (e.g., strain stiffening) closely mimic a biopolymer network such as collagen. − As PIC3eg undergoes transition into a hydrogel above 18 °C, it can be injected in a minimally invasive manner. Additionally, in an immunotherapeutic setting, 3D PIC3eg scaffolds have been successfully applied to deliver preactivated T cells in vivo .…”

mentioning

confidence: 99%

Immunofilaments Are Well Tolerated after Local or Systemic Administration in Mice

Weiss,

Classens,

Schluck

et al. 2024

ACS Pharmacol. Transl. Sci.

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The invention of nanosized biomaterials has paved the way for novel therapeutics that can manipulate cells on a nanoscale. Nanosized immunofilaments (IFs) are synthetic filamentous polymers consisting out of polyisocyanopeptides, which have been recently established as a powerful platform to activate specific immune cells in vivo such that they raise an antitumor immune response. However, toxicological effects or immunogenicity toward the IFs have not yet been investigated. In this study, we evaluated potential toxic or immunogenic effects in C57BL/6 mice upon intravenous or subcutaneous injection of nonfunctionalized IFs or immunostimulatory IFs over 30 days. We here present a detailed analysis of the gross pathology, hematological parameters, blood biochemistry, histology, and antibody-response against the IF backbone. Our results demonstrate that IFs do not induce severe acute or chronic toxicity in mice. After 30 days, we only found elevated IgG-titers in intravenously injected but not subcutaneously injected mice. In summary, we demonstrate that IFs can be administered into a living organism without adverse side effects, thereby establishing the safety of IFs as a therapeutic intervention.

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Injectable polyisocyanide hydrogel as healing supplement for connective tissue regeneration in an abdominal wound model

Cited by 10 publications

References 74 publications

Conductive Polyisocyanide Hydrogels Inhibit Fibrosis and Promote Myogenesis

Conductive Polyisocyanide Hydrogels Inhibit Fibrosis and Promote Myogenesis

Microenvironment with NIR-Controlled ROS and Mechanical Tensions for Manipulating Cell Activities in Wound Healing

Immunofilaments Are Well Tolerated after Local or Systemic Administration in Mice

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