Alginate-waterborne polyurethane 3D bioprinted scaffolds for articular cartilage tissue engineering.

Articular cartilage defects comprise a spectrum of diseases associated with degeneration or damage of the connective tissue present in particular joints, presenting progressive osteoarthritis if left untreated. In vitro tissue regeneration is an innovative treatment for articular cartilage injuries that is attracting not only clinical attention, but also great interest in the development of novel biomaterials, since this procedure involves the formation of a neotissue with the help of material support. In this work, functional alginate and waterborne polyurethane (WBPU) scaffolds have been developed for articular cartilage regeneration using 3D bioprinting technology. The particular properties of alginate-WBPU blends, like mechanical strength, elasticity and moistening, mimic the original cartilage tissue characteristics, being ideal for this application. To fabricate the scaffolds, mature chondrocytes were loaded into different alginate-WBPU inks with rheological properties suitable for 3D bioprinting. Bioinks with high alginate content showed better 3D printing performance, as well as structural integrity and cell viability, being most suitable for scaffolds fabrication. After 28 days of in vitro cartilage formation experiments, scaffolds containing 3.2 and 6.4 % alginate resulted in the maintenance of cell number in the range of 104 chondrocytes/scaffold in differentiated phenotypes, capable of synthesizing specialized extracellular matrix (ECM) up to 6 µg of glycosaminoglycans (GAG) and thus, showing a potential application of these scaffolds for in vitro regeneration of articular cartilage tissue.

Design of drug-loaded 3D printing biomaterial inks and tailor-made pharmaceutical forms for controlled release.

Curcumin and chloramphenicol are drugs with different solubility properties in physiological conditions due to their hydrophobic and hydrophilic structure, respectively. In this work, sodium alginate-cellulose nanofibers (SA-CNF) based inks loaded with curcumin and/or chloramphenicol have been developed for syringe extrusion 3D printing technology. Printability and shape fidelity of the drug-loaded inks were analyzed through rheological characterization. Suitable drug-loaded inks were 3D printed showing shape fidelity, and samples were either freeze-dried or crosslinked with Ca2+ and air-dried to achieve functional pharmaceutical forms with different morphological characteristics. In vitro drug delivery tests were carried out from the resulted forms and it was observed that the release performed faster in freeze-dried than in Ca2+ crosslinked/air-dried ones for all cases, resulting in two different methods for controlling drug delivery over time. The differences in aqueous solubility of the drugs, the different CNF content of the inks and the surface area of the samples also played an important role during drug delivery, involving strategies to control the release over an extended duration.

3D printed alginate-cellulose nanofibers based patches for local curcumin administration.

Alginate and nanocellulose are potential biomaterials to be employed as bioinks for three-dimensional (3D) printing. Alginate-cellulose nanofibers (A-CNF) formulations with CNF amounts up to 5 wt% were developed and rheologically characterized to evaluate their printability. Results showed that formulations with less than 3 wt% CNF did not present suitable characteristics to ensure shape fidelity after printing. Selected A-CNF bioinks were 3D printed and freeze-dried to obtain porous scaffolds. Morphological and mechanical analysis were performed, showing that CNF contributed to the reinforcement of the scaffolds and modulated their porosity. The applicability for drug delivery was evaluated by the addition of curcumin to printable A-CNF formulations. The curcumin loaded bioinks were successfully 3D printed in patches and the in vitro release tests showed that alginate and CNF played an important role in curcumin stabilization, whereas the CNF content and the disintegration of the scaffold were essential in the release kinetics.