Polymeric Biomaterials For 3D Printing In Medicine

3D printing is rocking the field of tissue engineering, regenerative medicine, and rehabilitation allowing fabrication of modular and patient-specific scaffolds, orthoses, and prosthesis with high structural complexity and design flexibility. Since Charles Hull initially developed 3D printing technology in 1984 using stereolithography, 3D printing has expanding at accelerating pace in a wide range of applications in medicine, including craniofacial implants, dental molds, prosthetic parts, on-demand medical equipment, surgical models, scaffolds for tissue regeneration, organ printing, implantable biosensors, and tissue models for drug discovery.

This is due to the potential of 3D printing to provide patientspecific designs, high structural complexity, and rapid ondemand fabrication at a low-cost. However, one of the major bottlenecks that limits the widespread acceptance of 3D printing for biomedical manufacturing is the lack of polymers, biomaterials, hydrogels, and bioinks functional for 3D printing, biocompatible, and more performing from the biomechanical point of view to meet the different needs.

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Although much progress has been made with 3D printing technology, there are still remarkable issues to overcome (such as standardization and integration of an entire biofabrication platform, software design, capabilities of the 3D printers, reproducibility, quality by design, biomaterials characterization, and regulatory hurdles) before it can be recognized as a conventional biofabrication technique in medicine and reach the medical market. Among these issues, the major bottleneck is the lack of heterogeneity biomaterials allowing their reliable clinical use.

Generally, printable materials as polymers, hydrogels, or bioinks must: (1) have adequate viscosity that allows being printable and structurally stable, (2) have the capability to form 3D structure within a few minutes, (3) have the possibility of being mechanically reinforced through UV irradiation, biological (e.g. transglutaminase, sortase, tyrosinase, lysil-amine oxidase), or chemical (e.g. Michael-type addition, thiolene reaction, orthogonal reaction) cross-linking, (4) have tunable mechanical properties, (5) be biocompatible, (6) have adequate degradation kinetics, (7) form nontoxic degradation byproducts, (8) be biomimetic, and (9) be able to control release molecules or drugs. In addition, biomaterial inks should be easily manufactured and processed, affordable, and commercially available.

In this context, 3D printing can transform healthcare through personalized medicine, thus improving patient compliance by tailoring the medication to the patient. This can be achieved through on-demand manufacturing in clinical settings to offer the best medical care .

3D printable materials
Solid polymers-based inks

Polymers are the most common types of biomaterials used in 3D printing technologies [57, 58], since they come in the form of filaments for fused deposition modeling (FDM), powder-beads for selective laser sintering (SLS), solutions for stereolithography (SLA), and gels for direct ink writing (DIW) (Fig. 2). Further, they are biocompatible, have tunable mechanical properties, degradation rates, and can be dissolved in rapidly evaporating organic solvents such as dichloromethane, tetrahydrofuran or dimethyl sulfoxide.

Fig. . Schematic representation of 3D printing techniques. (a) Fused deposition modeling (FDM), (b) stereolithography (SLA), (c) selective laser sintering (SLS), and (d) direct ink writing (DIW). Table 1. Common polymers used in 3D printing and their properties

Polymeric hydrogel-based inks

Hydrogels are 3D cross-linked polymer networks, which can absorb and retain large amounts of water (> 90%) . Commonly hydrogels are held together by: (1) hydrogen bonds; (2) electrostatic interactions; (3) hydrophobic interactions; (4) watermediated hydrogen bonds; (5) van der Waals interactions; (6) covalent cross-links; or (7) a combination of the above interactions . Hydrogels provide ideal “soft material” systems to mimic native extracellular matrix (ECM) microenvironments due to their biocompatibility, tunable mechanics, and degradation. Additionally, they are able to easily incorporate bioactive cues (i.e. RGDS, IKVAV, and DGEA) or other bio-molecular structures such as nucleic acids, fatty acids, glycans, and growth factors to form biomimetic supramolecular scaffolds . Finally, some hydrogels are shear-thinning and thixotropic: useful properties for bioprinting.

(Abstracted from Ref : https://www.sciencedirect.com/science/article/pii/S2666964121000060 )

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