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A Poroelastic Model of a Fibrous-Porous Tissue Engineering Scaffold.

ABSTRACT: Tissue engineering scaffolds are used in conjunction with stem cells for the treatment of various diseases. A number of factors provided by the scaffolds affect the differentiation of stem cells. Mechanical cues that are part of the natural cellular microenvironment can both accelerate the differentiation toward particular cell lineages or induce differentiation to an alternative cell fate. Among such factors, there are externally applied strains and mechanical (stiffness and relaxation time) properties of the extracellular matrix. Here, the mechanics of a fibrous-porous scaffold is studied by applying a coordinated modeling and experimental approach. A force relaxation experiment is used, and a poroelastic model associates the relaxation process with the fluid diffusion through the fibrous matrix. The model parameters, including the stiffness moduli in the directions along and across the fibers as well as fluid diffusion time, are estimated by fitting the experimental data. The time course of the applied force is then predicted for different rates of loading and scaffold porosities. The proposed approach can help in a reduction of the technological and experimental efforts to produce 3-D scaffolds for regenerative medicine as well as in a higher accuracy of the estimation of the local factors sensed by stem cells.

SUBMITTER: Yuan D

PROVIDER: S-EPMC5864912 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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A Poroelastic Model of a Fibrous-Porous Tissue Engineering Scaffold.

Yuan Daniel D Somers Sarah M SM Grayson Warren L WL Spector Alexander A AA

Scientific reports 20180322 1

Tissue engineering scaffolds are used in conjunction with stem cells for the treatment of various diseases. A number of factors provided by the scaffolds affect the differentiation of stem cells. Mechanical cues that are part of the natural cellular microenvironment can both accelerate the differentiation toward particular cell lineages or induce differentiation to an alternative cell fate. Among such factors, there are externally applied strains and mechanical (stiffness and relaxation time) pr ...[more]

PMID: 29568010

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Project description:Pore size is generally small in nanofibrous scaffolds prepared by electrospinning polymeric solutions. Increase of scaffold thickness leads to decrease in pore size, causing impediment to cell infiltration into the scaffolds during tissue engineering. In contrast, comparatively larger pore size can be realized in microfibrous scaffolds prepared from polymeric solutions at higher concentrations. Further, microfibrous scaffolds are conducive to infiltration of reparative M2 phenotype macrophages during in vivo/in situ tissue engineering. However, rise of mechanical properties of a fibrous scaffold with the increase of polymer concentration may limit the functionality of a scaffold-based, tissue-engineered heart valve. In this study, we developed microfibrous scaffolds from 14%, 16% and 18% (wt/v) polycaprolactone (PCL) polymer solutions prepared with chloroform solvent. Porcine valvular interstitial cells were cultured in the scaffolds for 14 d to investigate the effect of microfibers prepared with different PCL concentrations on the seeded cells. Further, fresh microfibrous scaffolds were implanted subcutaneously in a rat model for two months to investigate the effect of microfibers on infiltrated cells. Cell proliferation, and its morphologies, gene expression and deposition of different extracellular matrix proteins in the in vitro study were characterized. During the in vivo study, we characterized cell infiltration, and myofibroblast and M1/M2 phenotypes expression of the infiltrated cells. Among different PCL concentrations, microfibrous scaffolds from 14% solution were suitable for heart valve tissue engineering for their sufficient pore size and low but adequate tensile properties, which promoted cell adhesion to and proliferation in the scaffolds, and effective gene expression and extracellular matrix deposition by the cells in vitro. They also encouraged the cells in vivo for their infiltration and effective gene expression, including M2 phenotype expression.

Project description:Biodegradable tissue engineering scaffolds are commonly fabricated from poly(lactide-co-glycolide) (PLGA) or similar polyesters that degrade by hydrolysis. PLGA hydrolysis generates acidic breakdown products that trigger an accelerated, autocatalytic degradation mechanism that can create mismatched rates of biomaterial breakdown and tissue formation. Reactive oxygen species (ROS) are key mediators of cell function in both health and disease, especially at sites of inflammation and tissue healing, and induction of inflammation and ROS are natural components of the in vivo response to biomaterial implantation. Thus, polymeric biomaterials that are selectively degraded by cell-generated ROS may have potential for creating tissue engineering scaffolds with better matched rates of tissue in-growth and cell-mediated scaffold biodegradation. To explore this approach, a series of poly(thioketal) (PTK) urethane (PTK-UR) biomaterial scaffolds were synthesized that degrade specifically by an ROS-dependent mechanism. PTK-UR scaffolds had significantly higher compressive moduli than analogous poly(ester urethane) (PEUR) scaffolds formed from hydrolytically-degradable ester-based diols (p < 0.05). Unlike PEUR scaffolds, the PTK-UR scaffolds were stable under aqueous conditions out to 25 weeks but were selectively degraded by ROS, indicating that their biodegradation would be exclusively cell-mediated. The in vitro oxidative degradation rates of the PTK-URs followed first-order degradation kinetics, were significantly dependent on PTK composition (p < 0.05), and correlated to ROS concentration. In subcutaneous rat wounds, PTK-UR scaffolds supported cellular infiltration and granulation tissue formation, followed first-order degradation kinetics over 7 weeks, and produced significantly greater stenting of subcutaneous wounds compared to PEUR scaffolds. These combined results indicate that ROS-degradable PTK-UR tissue engineering scaffolds have significant advantages over analogous polyester-based biomaterials and provide a robust, cell-degradable substrate for guiding new tissue formation.

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Dataset Information

A Poroelastic Model of a Fibrous-Porous Tissue Engineering Scaffold.

Publications

A Poroelastic Model of a Fibrous-Porous Tissue Engineering Scaffold.

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