There’s a bioprinter in the building! – let’s get a project


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3D bioprinting is a novel and innovative method for the 3D fabrication of living tissue/organ-like structures through the deposition of small units of a substance known as a bioink. The bioprinting process relies on the deposition of either cell-laden droplets or cell embedding in a hydrogel to create such structures. The benefits from this technique include the reduced production times, an increased versatility, and the possibility to work under room temperature. Furthermore, this technology combined with patient’s medical imaging systems creates an opportunity of the fabrication of custom-made products. Such options could improve the match between implant and defect size, can reduce the time required for surgery and for patient recovery, and positively affect treatment success. In general, this possibility to tailor therapy, also known as personalized medicine, is promising for improving health care and, at the same time, decreasing costs.

 Healthcare improvement by 3D bioprinted cartilage

Today, the available scaffold options for bioinks are hydrogels, decellularized ECM (dECM), or microcarriers. Hydrogels are the most commonly used bioinks, due to their swelling and lubricating characteristics that best match with cartilage properties, and their potential to induce cells towards a chondrogenic phenotype. They are semi-liquid hydrophilic materials composed of a network of natural or synthetic cross-linked polymer chains. The gel consistency allows easy casting into the desired shapes and a uniform mixing with cells and growth factors. Depending on their origin, hydrogels can be natural or synthetic. Synthetic biocompatible hydrogels have a huge protentional in tissue engineering since their properties can be custom-designed in a more controllable manner than natural hydrogels.

As we know, the chondral and osteochondral lesions represent one of the most challenging and frustrating scenarios for the orthopedic, and oral and maxillofacial surgeons. Articular cartilage is a hyaline tissue covering bone ends to enable free movements. Joint tissues consequently tend to deteriorate. The issue is that cartilage lesions fail to heal spontaneously, leading to the development of chronic conditions, thereby reducing the quality of life and work capacity of patients, resulting in enormous costs for health and social care systems.

Things you must know about articular cartilage

Three-dimensional scaffold-based bioprinting holds the potential of cartilage tissue regeneration.and may provide a viable alternative to current treatment modalities. This technique displays important advantages to mimic natural cartilage over traditional methods by allowing a fine control of cell distribution, and the modulation of mechanical and chemical properties. It is well known that cartilage seemingly displays a simple structure, in fact, it is characterized by a zonal architecture defining specific mechanical properties which are very difficult to reproduce artificially. The “superficial zone” represents the top 10–20% of the cartilage and is characterized by the highest cell density. Just deep to it, the “middle zone” represents the next 40–60% of the cartilage, and the “deep zone” the bottom 30–40%, which then is in direct contact with the subchondral bone. Moving deeper from the “superficial zone”, there is a progressive decrease in cell density and an increase in the amount of glycosaminoglycan. Furthermore, the chondrocytes in the different zones differ. In the “superficial zone”, the cells are small and flattened, while in “deep zone”, the cells are larger and round. Additionally, different types of proteins are present in the articular cartilage, and their secretion and prevalence differ among zones. In the “superficial zone”, the most represented proteins are clusterin, proteoglycan-4, and Del-1, while in “middle zone”, cartilage intermediate layer protein (CILP) is at its peak. The specific distribution of these proteins probably contributes to the “zone-specific functionality” of the cartilage.

Some scientists question strategies based on the use of zonally harvested cells, considering these as overcomplicated. Therefore, they are working on approaches that are based on the use of a single cell source coupled with adequate biochemical and/or biomechanical stimuli. Stem cells, already demonstrated to be valuable mediators for tissue regeneration, are also promising candidates for this technology. Many studies have been conducted using adult stem cells derived from different sources such as bone marrow, adipose tissue, muscles, synovial membrane, trabecular bone, dermis, blood, periosteum, and perichondrium.

Bioprinting Articular cartilage

Hydrogels are defined as “water-swellable, yet water-insoluble, cross-linked networks” that can provide multiple advantages in tissue engineering as cell carriers for the creation of a multiple tissues. The 3D environment that they provide is able to maintain a high-water content, which resembles biological tissues and, therefore, facilitates cell proliferation. There are a multitude of natural polymers (i.e., collagen, chitosan, hyaluronic (HA) acid, silk proteins, gelatin, and alginates) that are widely used as hydrogel materials for tissue-engineering applications. The main limitation of these hydrogels for tissue engineering is their inability to maintain a uniform 3D structure. To overcome this problem, the synthetic hydrogels, such as peptide hydrogel might provide solution. Peptide hydrogel can also provide natural microenvironment for cells, which is considered paramount in cartilage tissue engineering. Therefore, these products might play a key role in 3d bioprinted cartilage research in the next few years.

Opportunities for Collaboration

As part of Biogelx Academic Collaboration Programme, we offer academic incentives to researchers interested in incorporating our synthetic 3d bioink materials into new projects. If you are in academia, have interests in the area of 3D Bioprinting and are looking to collaborate then contact us,  there is no cost to exploring potential collaboration opportunities.

 

Sources:

Livia Roseti et.a. (2018) Three-Dimensional Bioprinting of Cartilage by the Use of Stem Cells: A Strategy to Improve Regeneration Materials 11, 1749; doi:10.3390/ma11091749

Yu Liuet.al. (2017) Recent Progress in Cartilage Tissue Engineering—Our Experience and Future Directions EngineeringVolume 3, Issue 1https://doi.org/10.1016/J.ENG.2017.01.010

Di Bella C et.al. (2015) 3D bioprinting of cartilage for orthopedic surgeons: reading between the lines. Front. Surg. 2:39. doi: 10.3389/fsurg.2015.00039

 

 

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