3D bioprinting of cartilage for orthopaedic surgeons

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Printing techniques and materials which have the potential in this research area

Chondral and osteochondral lesions represent one of the most challenging scenarios for the orthopaedic surgeon and for the patient, as the current therapeutic strategies are not providing satisfactory results in restoring function or slowing the progression of osteoarthritis. Based on research outcomes in the recent years, tissue engineering seems to have the potential to address the issue of osteoarticular loss and provide a viable alternative to current treatments by applying 3d bioprinting techniques in the clinical environment.

It is known that cartilage injuries cannot heal spontaneously, and that any type of repair will be characterised by fibrocartilage i.e. scar tissue. This tissue lacks properties such as resistance to shear and compression which make hyaline cartilage so distinctive, and in turn leads to degenerative changes and arthritis.

Despite its simple appearance, cartilage is a tissue that is characterized by a composition exhibiting differences depending on the depth of the tissue, which makes it much complex than initially was thought.

Which bioprinting techniques work for osteoarticular tissues?

With the boom of 3D bioprinting, there has been widespread development of printers and additive manufacturing techniques, which allow the biofabrication of complex structures. These technologies include fused deposition modelling (FDM), stereolithography, extrusion printing, inkjet printing and laser-based techniques. With regards to cartilage regeneration, the hydrogel-based scaffolds are the main materials used due to their inherent compatibility with chondral tissue. Therefore, inkjet and extrusion printers are the most commonly used machines in cartilage tissue engineering. Having said this, it has been extrusion-based methods that have been most widely used in recent years. The popularity of this printing technique is most likely due to its simplicity, diversity, and predictability. Whilst in comparison to inkjet, for the moment extrusion-based bioprinting has lower speed and resolution, it offsets this by being able to offer advantages such as higher cell densities, a wider range of printable biomaterials (viscosity in the range of 30-6 x 107 mPa/s) and relatively inexpensive equipment.

Featured materials for cartilage bioprinting

Properties of bio-inks are also crucial for the development of functional living tissues such as cartilage by 3D bioprinting. Bio-inks based on the combination of scaffold and cells should satisfy biological features, biodegradability, and printability. Generally, available scaffold options for bio-inks are hydrogels, decellularized ECM (dECM) and microcarriers.

Hydrogels are water-swellable, yet water-insoluble, cross-linked networks. Often these are naturally-derived polymers, in which the 3D environment provided is able to maintain a high-water content, which resembles biological tissues and facilitates cell proliferation. The only limitation of such hydrogels for tissue engineering might be their inability to maintain a uniform 3D structure. However, researchers have been able to overcome this problem by applying synthetic hydrogels or natural-synthetic hydrogels hybrids.

Synthetic biocompatible polymers and peptides have been utilised to develop hydrogels for cartilage tissue engineering. Their properties can be controlled and custom-designed to match the requirements of a given cell type. This is especially true for peptide-based hydrogels., in which the physical and the biomimetic properties can be tailored.

It has been proven that chondrocytes change their function and morphology based on the ECM. Therefore, being able to provide the appropriate ECM structure is considered paramount in cartilage tissue engineering.

Peptide-based Hydrogel Inks

Synthetic ECM mimics are increasingly being used as they can provide solutions to some of the issues that naturally-derived materials pose. The main benefit of synthetic hydrogels is consistency. There should be no batch to batch variations as they are produced using known quantities, optimised procedure, and generally the chemistry of the polymer does not change unless required. As they are synthetic, there are no components from animal-derived sources which is an important factor for cell culture and tissue engineering research with the ultimate aim of clinical applicability.

BiogelxTMsynthetic 3D cell culture products have demonstrated the ability to improve the phenotype of chondrocytes differentiated from perivascular stem cells in the context of cartilage engineering. Based on these core products, Biogelx has designed a novel bioink family, which is printable at room temperature and do not require exposure to UV light, extreme temperature or pH changes.These new bioinks have been optimised for extrusion-based printing and are ideal for the development of cartilage bioprinting applications. The BiogelxTM-Ink products will be available from April. Watch this space for more info and details on the launch!



Roseti et.al. (2018) Three-Dimensional Bioprinting of Cartilage by the Use of Stem Cells: A Strategy to Improve Regeneration, Materials.

Bella et.al. (2015) 3D Bioprinting of Cartilage for Orthopedic Surgeons: Reading between the Lines, PubMed. DOI: 10.3389/fsurg.2015.00039

Derakhshanfar et.al. (2018) 3D bioprinting for biomedical devices and tissue engineering: A review of recent trends and advances, Bioactive Materials. volume 3, issue 2, page 144-156p, DOI: 10.1016/j.bioactmat.2017.11.008



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