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

Abstract

Osteoarthritis is a disease with a great socioeconomic impact and mainly affects articular cartilage, a tissue with reduced self-healing capacity. In this work, 3D printed 1,4 butanediol thermoplastic polyurethane (b-TPUe) scaffolds are functionalized and infrapatellar mesenchymal stem cells are used as the cellular source. Since b-TPUe is a biomaterial with mechanical properties similar to cartilage, but it does not provide the desired environment for cell adhesion, scaffolds are functionalized with two methods, one based on collagen type I and the other in 1-pyrenebutiric acid (PBA) as principal components. Alamar Blue and confocal assays display that PBA functionalized scaffolds support higher cell adhesion and proliferation for the first 21 days. However, collagen type I functionalization induces higher proliferation rates and similar cell viability than the PBA method. Further, both functionalization methods induce extracellular matrix synthesis, and the presence of chondrogenic markers (Sox9, Col2a, and Acan). Finally, SEM images probe that functionalized 3D printed scaffolds present much better cell/biomaterial interactions than controls and confirm early chondrogenesis. These results indicate that the two methods of functionalization in the highly hydrophobic b-TPUe enhance the cell-biomaterial interactions and the improvement in the chondro-inductive properties, which have great potential for application in cartilage tissue engineering.

Cell‐instructive biomaterials in tissue engineering and regenerative medicine

“…The synthetic material b‐TPUe shows promise for cartilage engineering, but it does not typically have sufficient bioactivity to allow for clinical use. This study showed that 3D printed b‐TPUe scaffolds decorated with collagen I or PBA had increased cell attachment and proliferation, increased chondrogenic differentiation potential without the use of differentiation medium or growth factors 65 …”

Emerging polymeric material strategies for cartilage repair

“…Regenerative engineering approaches to treat full thickness chondral defects or OCDs (extending from articular cartilage surface into the underlying subchondral bone) has garnered ample attention in recent literature (Table 2). [58][59][60][61][62][63][64][65][66][67][68][69][70][71] For example, Song et el. fabricated a templated hydrogel scaffold based on human-like collagen that exhibited an interconnected porous structure through the use of a bovine serum albumin (BSA) porogen.…”

“…3D printing may be used to obtain scaffolds with controlled architecture and arrangement of biochemical cues. [63][64][65][66][67][68][69][70][71] Castilho et al created a microfiber (polycaprolactone (PCL))-reinforced gelatin-methacrylate (GelMA) hydrogel wherein the microfibers were oriented in the direction of natural collagen fibers based on depth-wise properties. 66 This promoted cartilage-like stress relaxation, and the application of mechanical forces stimulated the production of collagen II and GAGs in the absence of bioactive factors.…”

“…Accordingly, NP-like properties were obtained (e.g., loss and storage E). Culture of the hydrogels with bovine NP cells were characterized 66 PCL -gelatin-methacryloyl (GelMA) | Critchley, 2020 65 PCL, poly(lactic acid) (PLA), or poly(lactic-co-glycolic acid) (PLGA) -alginate or agarose | Levato, 2017 64 GelMA | Li, 2021 71 Silk fibroin -gelatin-tyramine | Martinez-Moreno, 2022 63 1,4 Butanediol thermoplastic polyurethane -collagen type I or 1-pyrenebutiric acid | Nguyen, 2017 68 Nanofibrillated cellulose -alginate or hyaluronic acid | Nie, 2020 59 Decellularized allogeneic hyaline cartilage graft, | Qi, 2018 72 Sericin methacryloyl (SerMA) | Rathan, 2019 69 Cartilage derived extracellular matrix -alginate | Rothrauff, 2018 60 Methacrylate functionalized decellularized patella tendon or hyaline cartilage | Song, 2017 58 Human-like collagen | Wang, 2017 73 Star poly(ethylene glycol) | Xue, 2018 61 Decellularized cartilage sheets | Yang, 2018 70 Collagen type I -sodium alginate | Yin, 2018 62 Decellularized articular cartilage | by high viability and maintained metabolic activity. In the case of AF regeneration, polymeric materials have been used to form both injectable and implantable scaffolds.…”

“…Recent studies utilizing polymer scaffolds for articular cartilage regeneration[58][59][60][61][62][63][64][65][66][67][68][69][70][71][72][73][74] …”