Crosslinking strategies facilitate tunable structural properties of fibrin microthreads

Grasman, Jonathan M.; Page, Raymond; Dominko, Tanja; Pins, George D.

doi:10.1016/j.actbio.2012.07.018

Cited by 21 publications

(60 citation statements)

References 51 publications

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“…Fibrin microthreads were co-extruded from solutions of fibrinogen and thrombin using extrusion techniques described previously [15, 16]. Briefly, fibrinogen from bovine plasma (Sigma, St. Louis, MO; F8630) was dissolved in HEPES (N-[2-Hydroxyethyl]piperazine-N′-[2-ethanesulfonic acid]) buffered saline (HBS, 20 mM HEPES, 0.9% NaCl; pH 7.4) at 70 mg/mL and stored at -20 °C until use.…”

Section: Methodsmentioning

confidence: 99%

“…Stretch percentages were reported as the ratio between the deformation (ΔL) of the thread and the starting length (L 0 ) of the thread (stretch % = ΔL/L 0 *100%). Microthreads were fabricated using previously reported methods, which included static axial stretching of approximately 150% immediately after polymerization to form three 19 cm microthreads [16]. Hence these threads were designated as control threads.…”

Section: Methodsmentioning

confidence: 99%

“…Mechanical characterization of stretched fibrin microthreads was performed using techniques described previously [16]. Briefly, individual microthreads were affixed with medical grade silicone adhesive to vellum paper frames with precut windows that defined the region of loading.…”

Section: Methodsmentioning

confidence: 99%

“…Microthread degradation was performed on single fibers on the bottom of 48 well plates as previously described [16]. Briefly, stretched microthreads were cut into 0.8 cm fragments and secured to the bottom of 48 well plates using medical grade silicone adhesive.…”

Section: Methodsmentioning

confidence: 99%

“…Another advantage of creating microthreads from a dense fibrin matrix is to increase the mechanical strength of the overall fibrin scaffold [15]. To further augment the mechanical properties of fibrin microthreads, we have investigated UV crosslinking [15], and carbodiimide crosslinking [16] methods to enhance the tensile strength of fibrin microthreads, and showed that carbodiimide crosslinking increased the tensile strength of microthreads as well as their resistance to proteolytic degradation in vitro . The current fibrin microthread fabrication process involves stretching microthreads immediately after fibrin polymerization, which generates uniform scaffolds with repeatable structural properties; however, we are not aware of any systematic studies that analyze the effects of static axial stretching on the structural or functional properties of fibrin scaffolds, including fibrin microthreads.…”

Section: Introductionmentioning

confidence: 99%

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Static axial stretching enhances the mechanical properties and cellular responses of fibrin microthreads

et al. 2014

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Fibrin microthreads are a platform technology that can be used for a variety of applications, and therefore the mechanical requirements of these microthreads differ for each tissue or device application. To develop biopolymer microthreads with tunable mechanical properties, we analyzed fibrin microthread processing conditions to strengthen the scaffold materials without the use of exogenous crosslinking agents. Fibrin microthreads were extruded, dried, rehydrated, and static axially stretched 0-200% of their original lengths; then the mechanical and structural properties of the microthreads were assessed. Stretching significantly increased the tensile strength of microthreads threefold, yielding scaffolds with tensile strengths and stiffnesses that equaled or exceeded values reported previously for carbodiimide crosslinked threads without affecting intrinsic material properties such as strain hardening or Poisson's ratio. Interestingly, these stretching conditions did not affect the rate of proteolytic degradation of the threads. The swelling ratios of stretched microthreads decreased, and scanning electron micrographs showed increases in grooved topography with increased stretch, suggesting that stretching may increase the fibrillar alignment of fibrin fibrils. The average cell alignment with respect to the longitudinal axis of the microthreads increased twofold with increased stretch, further supporting the hypothesis that stretching microthreads increases the alignment of fibrin fibrils on the surfaces of the scaffolds. Together, these data suggest that stretching fibrin microthreads generates stronger materials without affecting their proteolytic stability, making stretched microthreads ideal for implantable scaffolds that require short degradation times and large initial loading properties. Further modifications to stretched microthreads, such as carbodiimide crosslinking, could generate microthreads to direct cell orientation and align tissue deposition, with additional resistance to degradation for use as a long-term scaffold for tissue regeneration.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Static axial stretching enhances the mechanical properties and cellular responses of fibrin microthreads

et al. 2014

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Development of fibrin conjugated chitosan/nano β‐TCP composite scaffolds with improved cell supportive property for bone tissue regeneration

Siddiqui

Pramanik

2014

J of Applied Polymer Sci

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In the present study, an attempt has been made to improve cell supportive property of chitosan/nano beta tri-calcium phosphate (b-TCP) composite scaffolds by modification of scaffold surface with fibrin using ethyl-3-(3-dimethylaminopropyl) carbodimide (EDC) as crosslinking agent. The developed fibrin conjugated chitosan/nano b-TCP composite scaffolds possess desired pore size and porosity in the range of 45-151 mm and 81.4 6 4.1%, respectively. No significant change in compressive strength of scaffolds was observed before and after fibrin conjugation. The calculated compressive strength of fibrin conjugated and non-conjugated chitosan/nano b-TCP scaffolds are 2.71 6 0.14 MPa and 2.67 6 0.11 MPa, respectively. Results of cell culture study have further shown an enhanced cell attachment, cell number, proliferation, differentiation, and mineralization on fibrin conjugated chitosan/nano b-TCP scaffold. The uniform cell distribution over the scaffold surface and cell infiltration into the scaffold pores were assessed by confocal laser scanning microscopy. Furthermore, higher expression of osteogenic specific genes such as bone sialo protein, osteonectin, alkaline phosphatase, and osteocalcin (OC) on fibrin conjugated scaffolds was observed when compared to scaffolds without fibrin. Altogether, results indicate the potentiality of developed fibrin conjugated composite scaffolds for bone tissue engineering applications.

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Etching anisotropic surface topography onto fibrin microthread scaffolds for guiding myoblast alignment

Carnes

Pins

2020

J Biomed Mater Res

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To regenerate functional muscle tissue, engineered scaffolds should impart topographical features to induce myoblast alignment by a phenomenon known as contact guidance. Myoblast alignment is an essential step towards myotube formation, which is guided in vivo by extracellular matrix structure and micron-scale grooves between adjacent muscle fibers. Fibrin microthread scaffolds mimic the morphological architecture of native muscle tissue and have demonstrated promise as an implantable scaffold for treating skeletal muscle injuries. While these scaffolds promote modest myoblast alignment, it is not sufficient to generate highly functional muscle tissue.The goal of this study is to develop and characterize a new method of etching the surface of fibrin microthreads to incorporate aligned, sub-micron grooves that promote myoblast alignment. To generate these topographic features, we placed fibrin microthreads into 2-(N-morpholino)ethane-sulfonic acid (MES) acidic buffer and evaluated the effect of buffer pH on the generation of these features. Surface characterization with atomic force microscopy and scanning electron microscopy indicated the generation of aligned, sub-micron sized grooves on microthreads in MES buffer with pH 5.0. Microthreads etched with surface features had tensile mechanical properties comparable to controls, indicating that the surface treatment does not inhibit scaffold bulk properties. Our data demonstrate that etching threads in MES buffer with pH 5.0 enhanced alignment and filamentous actin stress fiber organization of myoblasts on the surface of scaffolds. The ability to tune topographic features on the surfaces of scaffolds independent of mechanical properties provides a valuable tool for designing microthread-based scaffolds to enhance regeneration of functional muscle tissue.

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Crosslinking strategies facilitate tunable structural properties of fibrin microthreads

Cited by 21 publications

References 51 publications

Static axial stretching enhances the mechanical properties and cellular responses of fibrin microthreads

Static axial stretching enhances the mechanical properties and cellular responses of fibrin microthreads

Development of fibrin conjugated chitosan/nano β‐TCP composite scaffolds with improved cell supportive property for bone tissue regeneration

Etching anisotropic surface topography onto fibrin microthread scaffolds for guiding myoblast alignment

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