Growing bone substitute materials

Materials World magazine
,
4 Mar 2020

A new approach to an old method could help create structures that can repair damaged bones. Idha Valeur finds out how it works.

A several hundred years old system, chemobrionics, has enabled researchers to create materials that mimic the structure of bones.

Chemobrionics is the study of the formation of self-assembling macro, micro and nanostructures. The University of Birmingham, UK, Postdoctoral Research Fellow, Dr Erik Hughes, told Materials World that in this particular project, the team used a chemobrionics system to generate tubular calcium phosphate frameworks. ‘These structures not only imitate the functional tubular structures found in hard tissue, but they are also composed of bone-like mineral,’ he said.

The structures the team created are constructed in layers and made of a hydrogel loaded with calcium and built up with a phosphate solution. ‘The interface between the gel and solution reactant components facilitates the development of steep concentration, osmotic and pH gradients. The chemical driving force promotes the release of upward streams of calcium from the gel that enter phosphate solution,’ said Hughes. ‘This triggers a precipitation reaction that results in hollow tubes of calcium phosphate mineral. The growth of the tubes is driven completely by the thermodynamic disequilibrium between the gel and solution reactant components.’

Mineral breakdown

The replica material’s structure consists of hollow tubes of calcium phosphate that mimic the composition of human bone. The same mineral the team is growing, hydroxyapatite, is currently used for surgical bone replacements but now, Hughes is working on creating the same material by replacing conventional methods with bioinspired ones. The tubes are of the same thickness as one strand of human hair, and have a porous surface that encourages cell interaction. Their width and breadth can be changed by adjusting the reactant selection, ionic concentrations and pH, which influences the overall composition and subsequently change the hierarchical organisation of the tube walls.

‘Commercially available calcium phosphate bone substitutes are generally synthesised in a controlled laboratory environment. While chemically similar to bone, typically, the processing and treatments applied to these materials result in phases and structuring that is far removed from the tissue they are replacing,’ Hughes said.

Expanding on this, he explained that the calcium phosphate mineral synthesised in the lab and the new hydroxyapatite being grown are essentially the same, but the different techniques produce different formats of the final product. The existing product is delivered in sintered blocks and granules that a surgeon can use to fill a large bone defect, where the tissue will not heal naturally and so relies on surgical augmentation with substitutes. The team’s new method results in a powder that requires further processing in the clinical setting.

‘The sintering process the hydroxyapatite undergoes is a thermal treatment. It effectively results in a dense, highly crystalline hydroxyapatite product, whereas bone is typically poorly crystalline,’ said Hughes.

‘Our method results in structured hydroxyapatite composed of poorly crystalline hydroxyapatite. Future work will focus on development of bone substitutes composed entirely of or incorporating the chemobrionic frameworks themselves.’

Testing minerals

To test the material, the researchers used a variety of analytical methods to better understand the tubes’ composition and structure. ‘A combination of X-ray diffraction and Raman spectroscopy was used to confirm the phase and crystalline nature of the materials,’ said Hughes. ‘Importantly, we were particularly interested in how cells interacted with the tubular features. Key to this was the use scanning electron microscopy to probe the microstructure of the tube surface and additionally to image localised cell attachment and morphology.’

After 48 hours, the researchers showed that cells had spread both on and within the tubes. This indicated that the tubular structure is an ideal substrate for the attachment of stem cells. According to Hughes, ‘attached cells remained viable and furthermore demonstrated significant adaption to the topological features presented’.

From here, the team aims to develop a new class of chemobrionic biomaterials that can simulate new bone formation. Hughes said that at present, the team is investigating the formulation of chemobrionics biomaterials for treatment of fracture non-union and spinal fusion.