Validation of the 1,4‐butanediolthermoplastic polyurethane as a novel material for3Dbioprinting applications

Abstract

Background Tissue engineering (TE) seeks to fabricate implants that mimic the mechanical strength, structure, and composition of native tissues. Cartilage TE requires the development of functional personalized implants with cartilage-like mechanical properties capable of sustaining high loadbearing environments to integrate into the surrounding tissue of the cartilage defect. Objective In this study we evaluated the novel 1,4-Butanediol thermoplastic polyurethane elastomer (b-TPUe) derivative filament as a 3D bioprinting material with application in cartilage TE. Methods The mechanical behaviour of b-TPUe in terms of friction and elasticity were examined and compared with human articular cartilage, PCL, and PLA. Moreover, infrapatellar fat pad-derived human mesenchymal stem cells (MSCs) were bioprinted together with scaffolds. In vitro cytotoxicity, proliferative potential, cell viability, and chondrogenic differentiation were analysed by Alamar blue assay, SEM, confocal microscopy, and RT-qPCR. Moreover, in vivo biocompatibility and host integration were analysed. Results This article is protected by copyright. All rights reserved. b-TPUe demonstrated a much closer compression and shear behaviour to native cartilage than PCL and PLA, as well as closer tribological properties to cartilage. Moreover, b-TPUe bioprinted scaffolds were able to maintain proper proliferative potential, cell viability, and supported MSCs chondrogenesis. Finally, in vivo studies revealed no toxic effects 21 days after scaffolds implantation, extracellular matrix (ECM) deposition and integration within the surrounding tissue. Conclusions This is the first study that validates the biocompatibility of b-TPUe for 3D bioprinting. Our findings indicate that this biomaterial can be exploited for the automated biofabrication of artificial tissues with tailorable mechanical properties including the great potential for cartilage TE applications.

Chondro‐Inductive b‐TPUe‐Based Functionalized Scaffolds for Application in Cartilage Tissue Engineering

“…In the present work, 3D scaffolds were printed with b‐TPUe, a thermoplastic PU filament comprising methylene diphenyl diisocyanate (MDI) and 1,4‐Butanediol, where PU structure consists of three complex monomers: a macrodiol, a diisocyanate, and a chain extender, based on which several different PU materials can be synthesized. [ 39 ] In previous works, we have demonstrated the biocompatibility of b‐TPUe [ 40 ] and its similar cartilage mechanical behavior. [ 29 ] Here, the 3D printed b‐TPUe scaffolds were functionalized using two different methodologies based on collagen type I and PBA to improve their biological properties.…”

“…[50] Thereby, both functionalized methods reached good cell viability values for 21 days with no apparent difference between them, and obtained results were considerably higher than previous works. [29,40] Nevertheless, PBA is an inexpensive reagent and a fast process of functionalization that allows obtaining functionalized b-TPUe in 2 h instead of 3 days, which could be used to manufacture b-TPUe directly coated with PBA.…”

Advances in spray products for skin regeneration

“…3D bioprinting represents a very promising TE technique, with high flexibility and repeatability. Using computer-aided designs, biomaterials and living cells can be deposited layer by layer, fabricating custom-designed porous constructs as artificial skin tissues [ 1 , 96 ]. Bioprinting not only allows the generation of the different layers of the skin, but it also has the potential to include skin structures, such as sweat glands, vascular networks, and hair follicles, although this is still difficult to achieve.…”

Hyperelastic, shape‐memorable, and ultra‐cell‐adhesive degradable polycaprolactone‐polyurethane copolymer for tissue regeneration

“…[1][2][3][4][5] PU-based polymers have recently attracted substantial interest for use in various tissue-regenerative processes, including muscle, cartilage, blood vessel and bone regeneration, because of their tunable properties, such as biodegradability, elasticity and resistance to flex fatigue. [6][7][8][9][10] However, poor cell adhesiveness and the need for further bio-friendly surface modification due to the innate absence of functional groups from their original structures remain obstacles to the use of PU-based polymers as substrates for clinical tissue regeneration along with low biodegradability, [11][12][13][14][15] while cell attachment is considered the essential first step to trigger proliferation, migration and differentiation, which are prerequisites for tissue regeneration. 16,17 Myriad strategies have been attempted to increase the cell adhesiveness of PU-based polymers for use in clinical settings.…”

“…The growing demand for versatile, biocompatible synthetic polymers in biomedical engineering and medical devices has galvanized research beyond the biocompatibility and tissue‐regenerative ability of FDA‐approved synthetic polymers such as polycaprolactone (PCL), poly(methyl methacrylate) (PMMA), poly(lactic‐co‐glycolic acid) (PLGA), and polyurethanes (PU) and toward the design of more tailorable polymeric materials with enhanced biological and mechanical properties 1–5 . PU‐based polymers have recently attracted substantial interest for use in various tissue‐regenerative processes, including muscle, cartilage, blood vessel and bone regeneration, because of their tunable properties, such as biodegradability, elasticity and resistance to flex fatigue 6–10 . However, poor cell adhesiveness and the need for further bio‐friendly surface modification due to the innate absence of functional groups from their original structures remain obstacles to the use of PU‐based polymers as substrates for clinical tissue regeneration along with low biodegradability, 11–15 while cell attachment is considered the essential first step to trigger proliferation, migration and differentiation, which are prerequisites for tissue regeneration 16,17 …”