Influence of Fiber Stiffness on Meniscal Cell Migration into Dense Fibrous Networks

Song, Kwang Hoon; Heo, Su‐Jin; Peredo, Ana P.; Mauck, Robert L.; Burdick, Jason A.

doi:10.1002/adhm.201901228

Cited by 36 publications

(40 citation statements)

References 44 publications

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“…22,30 One of the important criteria required for meniscal regeneration is that the injected biomaterials should provide a suitable mechanical function. A recent study by Song et al 47 showed that the hydrogel with a stiff mechanical property allowed faster fibrochondrocyte migration to fill the meniscal tissue defect as compared with soft hydrogel. In this study, we simply introduced PEO, which has a high molecular weight polyethylene glycol (PEG; 100,000 g/mol) and is an FDA-approved biomaterial and which was selected because it can attract water molecules within the network structure for increased mechanical stability.…”

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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“…Current dynamic endothelial models applied the cells on a 2D flat surface-either a wall of a microchannel, the bottom of a reservoir, or a sealed porous membrane. However, some recent studies have shown that the biophysical cues of an ECM can affect cellular activities 13,[29][30][31] . Therefore, we hypothesized that the aligned fibrous topography (Fig.…”

Section: Resultsmentioning

confidence: 99%

A 3D-Printed, Modular, and Parallelized Microfluidic System with Customizable ECM Integration to Investigate the Roles of Basement Membrane Topography on Endothelial Cells

Jones¹,

Huang²,

Chung³

et al. 2020

Preprint

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Because dysfunctions of endothelial cells are involved in many pathologies, in vitro endothelial cell models for pathophysiological and pharmaceutical studies have been a valuable research tool. Although numerous microfluidic-based endothelial models have been reported, they had the cells cultured on a flat surface without considering the possible 3D structure of the native ECM. Endothelial cells rest on the basement membrane in vivo, which contains an aligned microfibrous topography. To better understand and model the cells, it is necessary to know if and how the fibrous topography can affect endothelial functions. With conventional fully integrated microfluidic apparatus, it is difficult to include additional topographies in a microchannel. Therefore, we developed a modular microfluidic system by 3D-printing and electrospinning, which enabled easy integration and switching of desired ECM topographies. Also, with standardized designs, the system allowed for high flow rates up to 4000 µL/min, which covered the full shear stress range for endothelial studies. We found that the aligned fibrous topography on the ECM altered arginine metabolism in endothelial cells, and thus increased nitric oxide production. To the best of our knowledge, this is the most versatile endothelial model that has been reported, and the new knowledge generated thereby lays a groundwork for future endothelial research and modeling.

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“…Additionally, stiffness and degradability do not only direct cell differentiation 54,55 , but also may influence invasion 32 . Biochemical cues such as receptor-binding peptides and CMPs have been shown to modulate cell bioactivity 56,57 .…”

Section: Discussionmentioning

confidence: 99%

“…Engineered hydrogels, such as functionalized poly(ethylene glycol) (PEG) hydrogels, are designed for delivery of targeted cellular instructions via tunable control of mechanical and biochemical environments [23][24][25][26] . Such cell-instructive hydrogels and scaffolds are attractive alternatives to cell-based tendon therapies because these materials do not rely on allogenic cell use and therefore reduce cell-donor site morbidity and immune rejection [27][28][29][30][31][32][33][34] .…”

Section: Introductionmentioning

confidence: 99%

Success Criteria for Preclinical Testing of Cell-Instructive Hydrogels for Tendon Regeneration

Locke

Ford

Silbernagel

et al. 2020

Preprint

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Tendon injuries are difficult to heal in part because intrinsic tendon healing, which is dominated by scar tissue formation, does not effectively regenerate the native structure and function of healthy tendon. Further, many current treatment strategies also fall short of producing regenerated tendon with the native properties of healthy tendon. There is increasing interest in the use of cell-instructive strategies to limit the intrinsic fibrotic response following injury and improve the regenerative capacity of tendon in vivo. We have established multi-functional, cell-instructive hydrogels for treating injured tendon that afford tunable control over the biomechanical, biochemical, and structural properties of the cell microenvironments. Specifically, we incorporated integrin-binding domains (RGDS) and assembled multi-functional collagen mimetic peptides (mfCMPs) that enable cell adhesion and elongation of stem cells within synthetic hydrogels of designed biomechanical properties and evaluated these materials using targeted success criteria developed for testing in mechanically-demanding environments like tendon healing. The in vitro and in situ success criteria were determined based on systematic reviews of the most commonly reported outcome measures of hydrogels for tendon repair and established standards for testing of biomaterials. We then showed, using validation experiments, that multi-functional and synthetic hydrogels meet these criteria. Specifically, these hydrogels have mechanical properties comparable to developing tendon; are non-cytotoxic both in 2D bolus exposure (hydrogel components) and 3D encapsulation (full hydrogel); are formed, retained, and visualized within tendon defects over time (two-weeks); and provide mechanical support to tendon defects at the time of injection and in situ formation. Ultimately, the in vitro and in situ success criteria evaluated in this study were designed for preclinical research to rigorously test the potential to achieve successful tendon repair prior to in vivo testing and indicate the promise of multi-functional and synthetic hydrogels for continued translation.

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Influence of Fiber Stiffness on Meniscal Cell Migration into Dense Fibrous Networks

Cited by 36 publications

References 44 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

A 3D-Printed, Modular, and Parallelized Microfluidic System with Customizable ECM Integration to Investigate the Roles of Basement Membrane Topography on Endothelial Cells

Success Criteria for Preclinical Testing of Cell-Instructive Hydrogels for Tendon Regeneration

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