Tunable fibrin-alginate interpenetrating network hydrogels to support cell spreading and network formation

Vorwald, Charlotte E.; Gonzalez-Fernandez, Tomas; Joshee, Shreeya; Sikorski, Pawel; Leach, J. Kent

doi:10.1016/j.actbio.2020.03.014

Cited by 64 publications

(38 citation statements)

References 37 publications

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“…However, it implies that when fibrin networks are subjected to deformation stress, there is a loss of high amounts of water and the network collapses [13]. is phenomenon is related to fiber structural changes at the molecular level and makes fibrin hydrogels unstable and difficult to manipulate [6,13,14]. e addition of particles has been largely used as a reinforcement strategy for polymers such as fibrin hydrogels [15].…”

Section: Introductionmentioning

confidence: 99%

“…This is important in nutrient diffusion processes. However, it implies that when fibrin networks are subjected to deformation stress, there is a loss of high amounts of water and the network collapses [ 13 ]. This phenomenon is related to fiber structural changes at the molecular level and makes fibrin hydrogels unstable and difficult to manipulate [ 6 , 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

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Improving Fibrin Hydrogels’ Mechanical Properties, through Addition of Silica or Chitosan-Silica Materials, for Potential Application as Wound Dressings

Becerra

Múnera

Galeano

et al. 2021

International Journal of Biomaterials

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Fibrin is a protein-based hydrogel formed during blood coagulation. It can also be produced in vitro from human blood plasma, and it is capable of resisting high deformations. However, after each deformation process, it loses high amounts of water, which subsequently makes it mechanically unstable and, finally, difficult to manipulate. The objective of this work was to overcome the in vitro fibrin mechanical instability. The strategy consists of adding silica or chitosan-silica materials and comparing how the different materials electrokinetic-surface properties affect the achieved improvement. The siliceous materials electrostatic and steric stabilization mechanisms, together with plasma protein adsorption on their surfaces, were corroborated by DLS and ζ-potential measurements before fibrin gelling. These properties avoid phase separation, favoring homogeneous incorporation of the solid into the forming fibrin network. Young’s modulus of modified fibrin hydrogels was evaluated by AFM to quantitatively measure stiffness. It increased 2.5 times with the addition of 4 mg/mL silica. A similar improvement was achieved with only 0.7 mg/mL chitosan-silica, which highlighted the contribution of hydrophilic chitosan chains to fibrinogen crosslinking. Moreover, these chains avoided the fibroblast growth inhibition onto modified fibrin hydrogels 3D culture observed with silica. In conclusion, 0.7 mg/mL chitosan-silica improved the mechanical stability of fibrin hydrogels with low risks of cytotoxicity. This easy-to-manipulate modified fibrin hydrogel makes it suitable as a wound dressing biomaterial.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Improving Fibrin Hydrogels’ Mechanical Properties, through Addition of Silica or Chitosan-Silica Materials, for Potential Application as Wound Dressings

Becerra

Múnera

Galeano

et al. 2021

International Journal of Biomaterials

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“…Furthermore, stiffer substrates appear to stimulate tubulogenesis in 2-dimensions, but stiffer 3-dimensional scaffolds abrogate vascular network formation. Other groups have used novel techniques, from the glycation of collagen [20] to the creation of alginate-based IPNs [52,53], to combat this inherent interdependency. However, these systems are based on chemical modification of a bio-adhesive polymer, which may disrupt bio-functionality.…”

Section: Discussionmentioning

confidence: 99%

Quantification of iPSC-derived vascular networks in novel phototunable angiogenic hydrogels

Crosby

Hillsley

Kumar

et al. 2020

Preprint

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Vascularization of engineered scaffolds remains a critical obstacle hindering the translation of tissue engineering from the bench to the clinic. Previously, we demonstrated the robust micro-vascularization of collagen hydrogels with induced pluripotent stem cell (iPSC)-derived endothelial progenitors; however, physically cross-linked collagen hydrogels compact rapidly and exhibit limited strength. To address these challenges, we synthesized an interpenetrating polymer network (IPN) hydrogel comprised of collagen and norbornene-modified hyaluronic acid (NorHA). This dual-network hydrogel combines the natural cues presented by collagen's binding sites and extracellular matrix (ECM)-mimicking fibrous architecture with the in situ modularity and chemical cross-linking of NorHA. We modulated the stiffness and degradability of this novel IPN hydrogel by varying the concentration and sequence, respectively, of the NorHA peptide cross-linker. Rheological characterization of the photo-mediated gelation process revealed that the stiffness of the IPN hydrogel increased with cross-linker concentration and was decoupled from the bulk NorHA content. Conversely, the swelling of the IPN hydrogel decreased linearly with increasing cross-linker concentration. Collagen microarchitecture remained relatively unchanged across cross-linking conditions, although the mere addition of NorHA delayed collagen fibrillogenesis. Upon iPSC-derived endothelial progenitor encapsulation, robust, lumenized microvascular networks developed in IPN hydrogels over two weeks. Subsequent computational analysis showed that an initial rise in stiffness increased the number of branch points and vessels, but vascular growth was suppressed in high stiffness IPN hydrogels. These results suggest that an IPN hydrogel consisting of collagen and NorHA is highly tunable, compaction resistant, and capable of stimulating angiogenesis.

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“…[ 6 ] Furthermore, the fibrin‐alginate interpenetrating networks seemed to exhibit well tunable mechanical and adhesive properties at varying fibrin concentrations. [ 19 ] Inspired by these results we triple‐modified alginate gels with Fe‐NPs, fibrin, and serum protein coatings (SPCs). Here, we were particularly interested in synergetic effects between the three types of modification and their impact on the physicochemical properties of alginate surface and the resulting cell behaviors.…”

Section: Introductionmentioning

confidence: 99%

Triple Modification of Alginate Hydrogels by Fibrin Blending, Iron Nanoparticle Embedding, and Serum Protein‐Coating Synergistically Promotes Strong Endothelialization

Richter

Rehbock

et al. 2021

Adv Materials Inter

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different available therapies, stent therapy is able to reduce both the morbidity and mortality of coronary heart disease and its acute complication, the myocardial infarction. Therefore, stent therapy has become the primary therapy for acute ST-elevation myocardial infarction. [2] Nevertheless, instent-restenosis resulting from thromboembolic events, neointimal hyperplasia, or neoatherosclerosis is still the limiting factor of successful invasive stent therapy. [3,4] The underlying pathomechanism of these failures includes delayed re-endothelialization and endothelial dysfunction which are further aggravated by hypersensitivity reactions to synthetic polymers resulting in chronic inflammation. [1,5] Therefore, the development of a biocompatible stent device enhancing functional endothelialization is highly required. Biological polymers, especially, are attracting more and more interest. Among those are protein-based polymers like fibrin [6] or polysaccharide-based polymers like alginic acid. [7] Alginate hydrogels have been suggested as biological stentcoatings since they have been characterized by high biocompatibility and a so-called "non-fouling" effect. [8] Due to the absence of any adhesive structures and high surface wettability, alginate Stent therapy can reduce both morbidity and mortality of chronic coronary stenosis and acute myocardial infarction. However, delayed re-endothelialization, endothelial dysfunction, and chronic inflammation are still unsolved problems. Alginate hydrogels can be used as a coating for stent surfaces; however, complete and fast endothelialization cannot be achieved. In this study, alginate hydrogels are modified by fibrin blending, iron nanoparticle (Fe-NP) embedding, and serum protein coating (SPC) while surface properties and endothelialization capacity are monitored. Only a triple, synergetic modification of the alginate coating by simultaneous I) fibrin blending, II) Fe-NP addition complemented by III) SPC is found to significantly improve endothelial cell viability (live-dead-staining) and proliferation (WST-8 assay). These conditions yield formation of closed endothelial cell monolayers and an up to threefold increase (p < 0.01) in viability, while, interestingly, no effect is found when the modifications (I)-(III) are conducted individually. This synergetic effect is attributed to an accumulation of agglomerated Fe-NP and serum proteins along fibrin fibers, observed via laser scanning microscopy tracking nanoparticle scattering and tetramethylrhodamine (TRITC)-albumin fluorescence. These synergetic effects can pave the way toward a novel strategy for the modification of various hydrogel-based biomaterials and biomaterial coatings.

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Tunable fibrin-alginate interpenetrating network hydrogels to support cell spreading and network formation

Cited by 64 publications

References 37 publications

Improving Fibrin Hydrogels’ Mechanical Properties, through Addition of Silica or Chitosan-Silica Materials, for Potential Application as Wound Dressings

Improving Fibrin Hydrogels’ Mechanical Properties, through Addition of Silica or Chitosan-Silica Materials, for Potential Application as Wound Dressings

Quantification of iPSC-derived vascular networks in novel phototunable angiogenic hydrogels

Triple Modification of Alginate Hydrogels by Fibrin Blending, Iron Nanoparticle Embedding, and Serum Protein‐Coating Synergistically Promotes Strong Endothelialization

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