Hierarchically porous nagelschmidtite bioceramic–silk scaffolds for bone tissue engineering

Abstract

Bioactive three-dimensional (3D) scaffolds play a key role in the repair or regeneration of large bone defects.There are many methods to prepare 3D scaffolds, among which the 3D-plotting technique is a promising strategy as the scaffolds prepared by this method possess not only improved mechanical properties and interconnectivity, but also ordered large-pore structure. However, the low cell attachment rate in the interior of the 3D-plotted scaffolds, especially for 3D-plotted bioceramic scaffolds, inhibits the osteogenesis of stem cells in the scaffolds both in vitro and in vivo. The aim of this study is to prepare hierarchically porous composite scaffolds in order to improve the cell attachment, and further stimulate the in vitro and in vivo osteogenesis. We successfully fabricated hierarchically porous bioceramic-silk (BC-silk) composite scaffolds by a combination of the 3D-plotting technique with the freeze-drying method, and further investigated the attachment, proliferation and osteogenic differentiation of bone marrow stromal cells (BMSCs) in the scaffolds as well as the in vivo osteogenesis of the prepared porous scaffolds. The results showed that the hierarchical structure in the composite scaffolds was composed of first-level pores (B1 mm) of the bioceramic scaffold and second-level pores (B50-100 mm) of the silk matrix. The prepared BC-silk composite scaffolds possessed excellent apatite-mineralization ability and mechanical properties with compressive strength up to 25 MPa. In addition, hierarchically porous BC-silk scaffolds presented significantly enhanced attachment rate of BMSCs, around 4 times that of pure BC scaffolds without hierarchical pore structures. BC-silk scaffolds with hierarchical pore structures showed distinctively improved cell proliferation, ALP activity and bone-related gene expression as compared to BC scaffolds without hierarchical pore structure. Furthermore, hierarchically porous BC-silk scaffolds significantly enhanced the formation of new bone in vivo as compared to BC scaffolds. Our results suggest that the combination of 3D-plotting with the freeze-drying method is a viable strategy to construct hierarchical pore structures in 3D-plotted scaffolds, and the hierarchical pore structure plays an important role in improving the in vitro and in vivo osteogenesis of 3D-plotted bioceramic scaffolds for bone regeneration application.

3D‐Plotted Beta‐Tricalcium Phosphate Scaffolds with Smaller Pore Sizes Improve In Vivo Bone Regeneration and Biomechanical Properties in a Critical‐Sized Calvarial Defect Rat Model

“…However, the challenging requirements of specific physicochemical properties and imprecise pore size of the macropores render 3D plotting still immature to sufficiently prepare bioceramic scaffolds. [17] Forming a paste with an appropriate viscosity is crucial for direct extrusion during the 3D plotting. Previously, many researchers created composites by adding synthetic or biological polymers [14b,18] to print inorganic materials.…”

Hierarchically porous materials: synthesis strategies and structure design

“…Hierarchically porous materials with high surface areas, high pore volume ratios, high accessibilities, ready mass transport properties and high storage capacities have been used in various applications where they show their superiority compared to simple porous materials in catalysis, [10][11][12][13][14][15][16] adsorption, [17][18][19][20][21] separation, 22,23 sensors, [24][25][26][27] energy and life sciences. [67][68][69][70][71][72][73][74] At first, hierarchically porous materials with multiple porosities over lengths in the micro, meso to macro ranges have been intensively used as catalysts and catalyst supports. [10][11][12][13][14][15][16] The introduction of micro-mesoporosity into a macroporous solid can provide accurate size and shape selectivities for reactants,…”

“…Drug delivery has an equal need for hierarchically porous media to promote large storage capacity and controlled delivery in both a spacial and temporal manner. [67][68][69][70][71][72][73][74] Due to their short solid-state diffusion lengths and large surface areas, a wide range of hierarchically structured porous materials have been utilized to improve the performances of FCs, [38][39][40][41][42][43][44][45]95,96 LIBs [53][54][55][56][57] and supercapacitor [46][47][48][49][50][51][52][135][136][137][138][139][140] and in other energy storage applications. [58][59][60][61][62][63][64][65][66] All of these emerging applications are summarized in Table 1.…”

A 3D-printed scaffold with MoS2 nanosheets for tumor therapy and tissue regeneration

“…Bioactive materials used for tissue regeneration should be highly porous to induce cell migration, nutrient transportation and tissue ingrowth. [19][20][21][22] Thus, we hypothesized that a porous MoS 2 scaffold may be able to treat large tumor-induced bone defects by harnessing its inherent photothermal properties and the osteogenic potential of porous scaffolds.…”

“…19,20 When implanted into bone defects in vivo, they can induce new bone ingrowth to rapidly promote osteo-integration and bone remodeling. Moreover, these scaffolds gradually degrade as new bone tissue is formed.…”