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Bioactive Glass Scaffolds for Bone Regeneration Print

Natural materials are renowned for their unique combination of outstanding mechanical properties and exquisite microstructure. For example, bone, cork, and wood are porous biological materials with high specific stiffness (stiffness per unit weight) and specific strength. The outstanding mechanical properties of these materials are attributed to their anisotropic structures, which have optimized strength-to-density and stiffness-to-density ratios. Working at ALS Beamline 8.3.2, researchers from Berkeley Lab and the Imperial College London have created bioactive glass scaffolds that mirror nature’s efficient materials. The three-dimensional glass scaffold is as porous as trabecular bone, has a compressive strength comparable to that of cortical bone, and a strength-to-porosity ratio higher than any previously reported scaffolds.

Customized Bone Substitutes

Recently, there has been increasing interest in using bioactive glass as a scaffold material for bone repair. It has vast potential for repair and regeneration of bone defects because the structure and chemistry of glasses can be tailored over a wide range by changing either their composition or their thermal or environmental processing history. The release of ions from bioactive glasses reportedly activates the expression of osteogenic genes and stimulates bone growth, or angiogenesis. The ease and efficiency with which scientists can control the chemical composition or processing history of bioactive glass, adding ions to impart specific properties, enables them to manage the degradation rate of the glass, creating attractive and compliant scaffold materials.

A variety of techniques have been used for the fabrication of glass scaffolds, including polymer foam replication, sol-gel, and freeze-casting; however, the low compressive strength of these scaffolds (0.2–28 MPa for porosity of 92–60%) limits their application in the repair of load-bearing bone defects. The technique used to assemble the scaffolds in this research is a direct-ink write assembly. This technique allows patterning and controlled fabrication, creating the scaffold following a computer model, and sintering the glass into the desired composition and shape. Therefore, it is possible to design glass scaffolds with variable degradation rates to match that of bone growth and remodeling.

 

A three-dimensional visualization of the sintered 6P53B glass scaffolds using synchrotron x-ray microcomputed tomography (left and top right) and a corresponding scanning electron microscopy image (bottom right).

Scientists are developing new materials and structures inspired by biological materials with properties to satisfy a variety of applications. The ability to develop porous constructs with high mechanical strength, for example, is important for a broad range of emerging applications, including filters, catalyst support, and tissue engineering scaffolds. Particularly for orthopedic surgery, the regeneration of large bone defects in load-bearing limbs remains a challenging problem. The compressive strength of cortical bone, primarily in the shaft of long bones and as the outer shell around trabecular bone, has been reported to be in the range of 100–150 MPa in the direction parallel to the axis of orientation (long axis). It is difficult to design and fabricate a construct that will combine the large pores necessary to promote bone regeneration while substituting for, at least temporarily, the tissue by maintaining these loads in vivo.

Porous metallic implants used for replacement in fractures have well-documented fixation problems, and unlike natural bone, cannot self-repair or adapt to changing physiological conditions. As a consequence, the implant becomes loose over time. Bioactive glass and ceramic alternatives have shown excellent potential in repair and regeneration of bone defects due to their ability to support bone cell growth, form strong bonds to both hard and soft tissues, and adjust their degradation rate while newly formed bone and tissue are being remodeled.

 

Compressive strength versus porosity of the 6P53B glass scaffolds sintered at 700 °C. Comparison with cortical and trabecular bone and literature values of porous glass and hydroxyapatite scaffolds. Each style of point corresponds to a different literature value.

Recently, researchers from Berkeley Lab and the Imperial College London worked at ALS Beamline 8.3.2 to emulate nature’s design by robocasting bioactive glass scaffolds. Robocasting, or direct-ink write assembly, is a layer-by-layer assembly technique used to build scaffolds with structures following computer designs, creating periodic patterning and controlled fabrication of the filaments into constructs with qualities similar to those of biological materials. The scaffold architecture can be optimized to achieve the desired mechanical response, accelerate the bone-regeneration process, and guide the formation of bone with the anatomic cortical-trabecular structure.

The final product is a three-dimensional glass scaffold whose compressive strength (136 MPa) is comparable to that of cortical bone, the compact, dense bone material that forms the outer shell of most bones. The scaffold’s porosity, or void fraction, is 60%, comparable to that of trabecular bone, the spongy material that comprises the inside of vertebra and the ends of longer bones and is the site of metabolic activity such as ion exchange and red blood cell production. The strength of this porous glass scaffold is ~100 times that of polymer scaffolds and 4–5 times that of ceramic and glass scaffolds with comparable porosities previously reported in the literature. The glass scaffold’s biological performance in both small animals (mice) and big (miniature pigs) is currently under systematic evaluation at the University of California, San Francisco.

The ability to create structures that are both strong and porous could make scaffold fabrication applicable in a wide array of applications, including tissue engineering, filtration, and catalyst support. The use of glass also opens new possibilities in the field of bone regeneration, utilizing the easily tailored bioactivity and biodegradation rates, as well as the release kinetics of different ions, to achieve materials with the desired properties.


 

Research conducted by Q. Fu and A.P. Tomsia (Berkeley Lab) and E. Saiz (Imperial College London).

Research funding: National Institutes of Health. Operation of the ALS is supported by the U.S. Department of Energy, Office of Basic Energy Sciences.

Publications about this research: Q. Fu, E. Saiz, and A.P. Tomsia, “Bioinspired strong and highly porous glass scaffolds,” Adv. Funct. Mater. 21, 1058 (2011); Q. Fu, E. Saiz, and A.P. Tomsia, “Direct ink writing of highly porous and strong glass scaffolds for load-bearing bone defects repair and regeneration,” Acta Biomater. 7, 3547 (2011).

ALS Science Highlight #236

 

ALSNews Vol. 324