Fibrin Matrices as (Injectable) Biomaterials: Formation, Clinical Use, and Molecular Engineering

Roberts, Iwan; Bukhary, Deena M.; Leon‐Valdivieso, Christopher Y.; Tirelli, Nicola

doi:10.1002/mabi.201900283

Cited by 48 publications

(39 citation statements)

References 268 publications

(277 reference statements)

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“…Fb-based materials are currently being commercialized as surgical glue and are utilized for a variety of biomedical applications. 43 One of the key limitations of Fb is that upon injection, it can undergo rapid degradation. Even though the concentrations of fibrinogen and thrombin can be adjusted to achieve increased resistance to biodegradation, Fb hydrogel alone has limited mechanical properties.…”

Section: Discussionmentioning

confidence: 99%

Injectable Fibrin/Polyethylene Oxide Semi-IPN Hydrogel for a Segmental Meniscal Defect Regeneration

Kim

Yim

et al. 2021

Am J Sports Med

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Background: Meniscal deficiency from meniscectomy is a common situation in clinical practices. Regeneration of the deficient meniscal portion, however, is still not feasible. Purpose: To develop an injectable hydrogel system consisting of fibrin (Fb) and polyethylene oxide (PEO) and to estimate its clinical potential for treating a segmental defect of the meniscus in a rabbit meniscal defect model. Study Design: Controlled laboratory study. Methods: The Fb/PEO hydrogel was fabricated by extruding 100 mg·mL-1 of fibrinogen solution and 2,500 U·mL-1 of thrombin solution containing 100 mg·mL-1 of PEO through a dual-syringe system. The hydrogels were characterized by rheological analysis and biodegradation tests. The meniscal defects of New Zealand White male rabbits were generated by removing 60% of the medial meniscus from the anterior side. The removed portion included the central portion. The Fb/PEO hydrogel was injected into the meniscal defect of the experimental knee through the joint space between the femoral condyle and tibial plateau at the anterior knee without a skin incision. The entire medial menisci from both knees of each rabbit were collected and photographed before placement in formalin for histological processing. Hematoxylin and eosin, safranin O, and immunohistochemical staining for type II collagen was performed. The biomechanical property of the regenerated meniscus was evaluated using a universal tensile machine. Results: The Fb/PEO hydrogel was fabricated by an in situ gelation process, and the hydrogel displayed a semi-interpenetrating polymer network structure. We demonstrated that the mechanical properties of Fb-based hydrogels increased in a PEO-dependent manner. Furthermore, the addition of PEO delayed the biodegradation of the hydrogel. Our in vivo data demonstrated that, as compared with Fb hydrogel, Fb/PEO hydrogel injection into the meniscectomy model showed improved tissue regeneration. The regenerated meniscal tissue by Fb/PEO hydrogel showed enhanced tissue quality, which was supported by the histological and biomechanical properties. Conclusion: The Fb/PEO hydrogel had an effective tissue-regenerative ability through injection into the in vivo rabbit meniscal defect model. Clinical Relevance: This injectable hydrogel system can promote meniscal repair and be readily utilized in clinical application.

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Section: Discussionmentioning

confidence: 99%

Injectable Fibrin/Polyethylene Oxide Semi-IPN Hydrogel for a Segmental Meniscal Defect Regeneration

Kim

Yim

et al. 2021

Am J Sports Med

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“…Thus, fibrin hydrogels can serve as an effective delivery system for various types of applications. In parallel, fibrin is also one of the primary biological scaffolds used to culture cells for tissue engineering [5,[9][10][11][12][13], as it exhibits excellent biocompatibility, biodegradability, and tunable gel porosity and rigidity, while having the ability to be delivered in injectable or non-injectable forms to the damaged tissue [2,3,9,14]. However, although fibrin is often combined with both cells and therapeutic molecules, it remains unknown how the presence of cells affects drug release profiles.…”

Section: Introductionmentioning

confidence: 99%

FITC-Dextran Release from Cell-Embedded Fibrin Hydrogels

et al. 2021

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Fibrin hydrogel is a central biological material in tissue engineering and drug delivery applications. As such, fibrin is typically combined with cells and biomolecules targeted to the regenerated tissue. Previous studies have analyzed the release of different molecules from fibrin hydrogels; however, the effect of embedded cells on the release profile has yet to be quantitatively explored. This study focused on the release of Fluorescein isothiocyanate (FITC)-dextran (FD) 250 kDa from fibrin hydrogels, populated with different concentrations of fibroblast or endothelial cells, during a 48-h observation period. The addition of cells to fibrin gels decreased the overall release by a small percentage (by 7–15% for fibroblasts and 6–8% for endothelial cells) relative to acellular gels. The release profile was shown to be modulated by various cellular activities, including gel degradation and physical obstruction to diffusion. Cell-generated forces and matrix deformation (i.e., densification and fiber alignment) were not found to significantly influence the release profiles. This knowledge is expected to improve fibrin integration in tissue engineering and drug delivery applications by enabling predictions and ways to modulate the release profiles of various biomolecules.

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“…Specifically, we use confocal fluorescent microscopy to acquire volume-stack images of single fibroblast cells embedded in fibrin gels. This gel is commonly used to grow cells in 3D soft matrix, which reflects tissue environment [53,54]. The process is schematically illustrated in Fig 1. 2.1 Biological sample preparation 2.1.1 Cell culture.…”

Section: Methodsmentioning

confidence: 99%

Motion magnification analysis of microscopy videos of biological cells

et al. 2020

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It is well recognized that isolated cardiac muscle cells beat in a periodic manner. Recently, evidence indicates that other, non-muscle cells, also perform periodic motions that are either imperceptible under conventional lab microscope lens or practically not easily amenable for analysis of oscillation amplitude, frequency, phase of movement and its direction. Here, we create a real-time video analysis tool to visually magnify and explore sub-micron rhythmic movements performed by biological cells and the induced movements in their surroundings. Using this tool, we suggest that fibroblast cells perform small fluctuating movements with a dominant frequency that is dependent on their surrounding substrate and its stiffness.

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Fibrin Matrices as (Injectable) Biomaterials: Formation, Clinical Use, and Molecular Engineering

Cited by 48 publications

References 268 publications

Injectable Fibrin/Polyethylene Oxide Semi-IPN Hydrogel for a Segmental Meniscal Defect Regeneration

Injectable Fibrin/Polyethylene Oxide Semi-IPN Hydrogel for a Segmental Meniscal Defect Regeneration

FITC-Dextran Release from Cell-Embedded Fibrin Hydrogels

Motion magnification analysis of microscopy videos of biological cells

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