3D Biomimetic Scaffolds Research Articles

Chemotaxis of mesenchymal stem cells within 3D biomimetic scaffolds—a modeling approach

Bone tissue engineering is a promising strategy to repair local defects by implanting biodegradable scaffolds which undergo remodeling and are replaced completely by autologous bone tissue. Here, we consider a Keller–Segel model to describe the chemotaxis of bone marrow-derived mesenchymal stem cells (BMSCs) into a mineralized collagen scaffold. Following recent experimental results in bone healing, demonstrating that a sub-population of BMSCs can be guided into 3D scaffolds by gradients of signaling molecules such as SDF‐ 1 α , we consider a population of BMSCs on the surface of the pore structure of the scaffold and the chemoattractant SDF‐ 1 α within the pores. The resulting model is a coupled bulk/surface model which we reformulate following a diffuse-interface approach in which the geometry is implicitly described using a phase-field function. We explain how to obtain such an implicit representation and present numerical results on μ CT‐data for real scaffolds, assuming a diffusion of SDF‐ 1 α being coupled to diffusion and chemotaxis of the cells towards SDF‐ 1 α . We observe a slowing-down of BMSC ingrowth after the scaffold becomes saturated with SDF‐ 1 α , suggesting that a slow release of SDF‐ 1 α avoiding an early saturation is required to enable a complete colonization of the scaffold. The validation of our results is possible via SDF‐ 1 α release from injectible carrier materials, and an adaption of our model to similar coupled bulk/surface problems such as remodeling processes seems attractive.

Fabrication and evaluation of biomimetic scaffolds by using collagen–alginate fibrillar gels for potential tissue engineering applications

Pore architecture and its stable functionality under cell culturing of three dimensional (3D) scaffolds are of great importance for tissue engineering purposes. In this study, alginate was incorporated with collagen to fabricate collagen–alginate composite scaffolds with different collagen/alginate ratios by lyophilizing the respective composite gels formed via collagen fibrillogenesis in vitro and then chemically crosslinking. The effects of alginate amount and crosslinking treatment on pore architecture, swelling behavior, enzymatic degradation and tensile property of composite scaffolds were systematically investigated. The relevant results indicated that the present strategy was simple but efficient to fabricate highly interconnected strong biomimetic 3D scaffolds with nanofibrous surface. NIH3T3 cells were used as a model cell to evaluate the cytocompatibility, attachment to the nanofibrous surface and porous architectural stability in terms of cell proliferation and infiltration within the crosslinked scaffolds. Compared with the mechanically weakest crosslinked collagen sponges, the cell-cultured composite scaffolds presented a good porous architecture, thus permitting cell proliferation on the top surface as well as infiltration into the inner part of 3D composite scaffolds. These composite scaffolds with pore size ranging from 150 to 300μm, over 90% porosity, tuned biodegradability and water-uptake capability are promising for tissue engineering applications.

Strategies for cell manipulation and skeletal tissue engineering using high-throughput polymer blend formulation and microarray techniques

A combination of high-throughput material formulation and microarray techniques were synergistically applied for the efficient analysis of the biological functionality of 135 binary polymer blends. This allowed the identification of cell-compatible biopolymers permissive for human skeletal stem cell growth in both in vitro and in vivo applications. The blended polymeric materials were developed from commercially available, inexpensive and well characterised biodegradable polymers, which on their own lacked both the structural requirements of a scaffold material and, critically, the ability to facilitate cell growth. Blends identified here proved excellent templates for cell attachment, and in addition, a number of blends displayed remarkable bone-like architecture and facilitated bone regeneration by providing 3D biomimetic scaffolds for skeletal cell growth and osteogenic differentiation. This study demonstrates a unique strategy to generate and identify innovative materials with widespread application in cell biology as well as offering a new reparative platform strategy applicable to skeletal tissues.

Phase separation, pore structure, and properties of nanofibrous gelatin scaffolds

The development of three-dimensional (3D) biomimetic scaffolds which provide an optimal environment for cells adhesion, proliferation and differentiation, and guide new tissue formation has been one of the major goals in tissue engineering. In this work, a processing technique has been developed to create 3D nanofibrous gelatin (NF-gelatin) scaffolds, which mimic both the physical architecture and the chemical composition of natural collagen. Gelatin matrices with nanofibrous architecture were first created by using a thermally induced phase separation (TIPS) technique. Macroporous NF-gelatin scaffolds were fabricated by combining the TIPS technique with a porogen-leaching process. The processing parameters were systematically investigated in relation to the fiber diameter, fiber length, surface area, porosity, pore size, interpore connectivity, pore wall architecture, and mechanical properties of the NF-gelatin scaffolds. The resulting NF-gelatin scaffolds possess high surface areas (>32 m 2/g), high porosities (>96%), well-connected macropores, and nanofibrous pore wall structures. The technique advantageously controls macropore shape and size by paraffin spheres, interpore connectivity by assembly conditions (time and temperature of heat treatment), pore wall morphology by phase separation and post-treatment parameters, and mechanical properties by polymer concentration and crosslinking density. Compared to commercial gelatin foam (Gelfoam ®), the NF-gelatin scaffold showed much better dimensional stability in a tissue culture environment. The NF-gelatin scaffolds, therefore, are excellent scaffolds for tissue engineering.

Indirect solid free form fabrication of local and global porous, biomimetic and composite 3D polymer-ceramic scaffolds

Precise control over scaffold material, porosity, and internal pore architecture is essential for tissue engineering. By coupling solid free form (SFF) manufacturing with conventional sponge scaffold fabrication procedures, we have developed methods for casting scaffolds that contain designed and controlled locally porous and globally porous internal architectures. These methods are compatible with numerous bioresorbable and non-resorbable polymers, ceramics, and biologic materials. Phase separation, emulsion-solvent diffusion, and porogen leaching were used to create poly( l)lactide (PLA) scaffolds containing both computationally designed global pores (500, 600, or 800 μm wide channels) and solvent fashioned local pores (50–100 μm wide voids or 5–10 μm length plates). Globally porous PLA and polyglycolide/PLA discrete composites were made using melt processing. Biphasic scaffolds with mechanically interdigitated PLA and sintered hydroxyapatite regions were fabricated with 500 and 600 μm wide global pores. PLA scaffolds with complex internal architectures that mimicked human trabecular bone were produced. Our indirect fabrication using casting in SFF molds provided enhanced control over scaffold shape, material, porosity and pore architecture, including size, geometry, orientation, branching, and interconnectivity. These scaffolds that contain concurrent local and global pores, discrete material regions, and biomimetic internal architectures may prove valuable for multi-tissue and structural tissue interface engineering.