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

Abstract

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.

Collagen-Calcium Phosphate Cement Scaffolds Seeded with Umbilical Cord Stem Cells for Bone Tissue Engineering

“…[1][2][3][4][5][6] Bone is the most implanted tissue after blood. 7 Nearly seven million bone fractures occur annually in the United States alone.…”

Screening of 3D biomaterials- A New Dimension in Biomaterials Research (or two?)

“…Chatterjee et al fabricated macroporous3D scaffolds with varying chemical compositions were formed via salt leaching and were used to examine the response of osteoblasts to chemical composition in 3D [7]. The same group also developed apoly (ethylene glycol) dimethacrylate hydrogel system was used to encapsulate osteoblasts and examine the effect of scaffold modulus [8]. Hydrogels were also utilised by Yang et al to study the effect of different ECM proteins on embryonic stem cell differentiation [9].…”

An Improved Cryosection Method for Polyethylene Glycol Hydrogels Used in Tissue Engineering

“…Due to their rich water content and polymeric structure, hydrogels can mimic the physiological environments to support long-term survival of numerous cell types [1][2][3][4] and can provide three-dimensional frameworks to direct cellular behaviors and interactions. [5][6][7] Polyethylene glycol (PEG) is a synthetic bioinert polymer that has no innate cell adhesiveness and biological activity; however, PEG can be easily functionalized with bioactive peptide sequences or proteins, such as RGD or BMP-2, to present biological cues and stimulate cell behaviors. 8,9 Inclusion of cell process-catalyzed degradable crosslinking molecules, such as matrix metalloprotease (MMP)-sensitive peptides, can further promote the remodeling of the basic PEG polymeric structures and mediate native cellular matrix deposition.…”