Scaffold Modulus Research Articles

The effect of 3D hydrogel scaffold modulus on osteoblast differentiation and mineralization revealed by combinatorial screening

Cells are known to sense and respond to the physical properties of their environment and those of tissue scaffolds. Optimizing these cell–material interactions is critical in tissue engineering. In this work, a simple and inexpensive combinatorial platform was developed to rapidly screen three-dimensional (3D) tissue scaffolds and was applied to screen the effect of scaffold properties for tissue engineering of bone. Differentiation of osteoblasts was examined in poly(ethylene glycol) hydrogel gradients spanning a 30-fold range in compressive modulus (≈10 kPa to ≈300 kPa). Results demonstrate that material properties (gel stiffness) of scaffolds can be leveraged to induce cell differentiation in 3D culture as an alternative to biochemical cues such as soluble supplements, immobilized biomolecules and vectors, which are often expensive, labile and potentially carcinogenic. Gel moduli of ≈225 kPa and higher enhanced osteogenesis. Furthermore, it is proposed that material-induced cell differentiation can be modulated to engineer seamless tissue interfaces between mineralized bone tissue and softer tissues such as ligaments and tendons. This work presents a combinatorial method to screen biological response to 3D hydrogel scaffolds that more closely mimics the 3D environment experienced by cells in vivo.

Tailoring the mechanical properties of 3D‐designed poly(glycerol sebacate) scaffolds for cartilage applications

Matching tissue engineering scaffold modulus to that of native tissue is highly desirable. Effective scaffold modulus can be altered through changes in base material modulus and/or scaffold pore architecture. Because the latter may be restricted by tissue in-growth requirements, it is advantageous to be able to alter the base material modulus of a chosen scaffold material. Here, we show that the bulk modulus of poly(glycerol sebacate) (PGS) can be changed by varying molar ratios during prepolymer synthesis and by varying curing time. We go on to show that PGS can be used to create 3D designed scaffolds via solid freeform fabrication methods with modulus values that fall within the ranges of native articular cartilage equilibrium modulus. Furthermore, using base material modulus inputs, homogenization finite element analysis can effectively predict the tangent modulus of PGS scaffold designs, which provides a significant advantage for designing new cartilage regeneration scaffolds. Lastly, we demonstrate that this relatively new biomedical material supports cartilaginous matrix production by chondrocytes in vitro. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res, 2010.

Parametric Finite Element Analysis of Physical Stimuli Resulting From Mechanical Stimulation of Tissue Engineered Cartilage

While mechanical stimulation of cells seeded within scaffolds is widely thought to be beneficial, the amount of benefit observed is highly variable between experimental systems. Although studies have investigated specific experimental loading protocols thought to be advantageous for cartilage growth, less is known about the physical stimuli (e.g., pressures, velocities, and local strains) cells experience during these experiments. This study used results of a literature survey, which looked for patterns in the efficacy of mechanical stimulation of chondrocyte seeded scaffolds, to inform the modeling of spatial patterns of physical stimuli present in mechanically stimulated constructs. The literature survey revealed a large variation in conditions used in mechanical loading studies, with a peak to peak strain of 10% (i.e., the maximum amount of deformation experienced by the scaffold) at 1 Hz on agarose scaffolds being the most frequently studied parameters and scaffold. This loading frequency was then used as the basis for simulation in the finite element analyses. 2D axisymmetric finite element models of 2x4 mm2 scaffolds with 360 modulus/permeability combinations were constructed using COMSOL MULTIPHYSICS software. A time dependent coupled pore pressure/effective stress analysis was used to model fluid/solid interactions in the scaffolds upon loading. Loading was simulated using an impermeable frictionless loader on the top boundary with fluid and solid displacement confined to the radial axis. As expected, all scaffold materials exhibited classic poro-elastic behavior having pressurized cores with low fluid flow and edges with high radial fluid velocities. Under the simulation parameters of this study, PEG scaffolds had the highest pressure and radial fluid velocity but also the lowest shear stress and radial strain. Chitosan and KLD-12 simulated scaffold materials had the lowest radial strains and fluid velocities, with collagen scaffolds having the lowest pressures. Parametric analysis showed maximum peak pressures within the scaffold to be more dependent on scaffold modulus than on permeability and velocities to depend on both scaffold properties similarly. The dependence of radial strain on permeability or modulus was more complex; maximum strains occurred at lower permeabilities and moduli, and the lowest strain occurred at the stiffest most permeable scaffold. Shear stresses within all scaffolds were negligible. These results give insight into the large variations in metabolic response seen in studies involving mechanical stimulation of cell-seeded constructs, where the same loading conditions produce very different results due to the differences in material properties.

Uncoupled investigation of scaffold modulus and mesh size on smooth muscle cell behavior

Although scaffold material properties are known to critically impact cell behavior, it has proven difficult to correlate specific cell responses to isolated scaffold parameters, inhibiting rational design of scaffold material properties. The aim of this study was to validate a systematic approach for evaluating the influence of initial scaffold modulus and mesh size on cell extracellular matrix (ECM) deposition and phenotype. Poly(ethylene glycol) diacrylate (PEGDA) hydrogels were selected for this study because of their tunable material properties. Following screening of six distinct PEGDA hydrogels, three formulations were identified which permitted uncoupled investigation of scaffold mesh size and modulus within the target incremental modulus range of approximately 100-300 kPa. Smooth muscle cells (SMCs) were encapsulated within these three formulations, and cell ECM deposition and phenotype were evaluated following 21 days of culture. Although elastin content appeared to be correlated with scaffold mesh size and modulus to a similar degree, levels of collagen and serum response factor (SRF), a key regulator of SMC phenotype, were more strongly correlated with mesh size. To gain insight into the cell signaling underlying these observed correlations, variations in cell metabolic state and in RhoA signaling were semi-quantitatively evaluated. Both RhoA activity, which is largely modulated by scaffold mechanics in 2D, and cell metabolic activity were highly correlated with hydrogel mesh size. These results indicate that the effects of scaffold mechanics on RhoA activity in 3D may be distinct from those in 2D and underscore the need for uncoupled investigation of scaffold parameters on cell behavior. Furthermore, the present data suggest that RhoA signaling and cell metabolic regulation may be closely linked.

Electrospun PCL in Vitro: a Microstructural Basis for Mechanical Property Changes

Polymeric tissue-engineering scaffolds must provide mechanical support while host-appropriate cells populate the structure and deposit extracellular matrix (ECM) components specific to the organ targeted for replacement. Even though this concept is widely shared, changes in polymer modulus and other mechanical properties versus biological exposure are largely unknown. This work shows that specific interactions of biological milieu with electrospun scaffolds can exert control over scaffold modulus. The net effects of biological and non-biological environments on electrospun structures following 7 and 28 days of in vitro exposure are established. Reduction of modulus, ultimate tensile strength and elongation occurs without the apparent involvement of classic hydrolysis mechanisms. We describe this phenomenon as deposition-induced inhibition of nanofiber rearrangement. This phenomenon shows that both mechanical and morphological characterization of electrospun structure under load in biological environments is required to tailor scaffold design to pursue specific tissue-engineering goals.