title: Mechanical Properties, Cytocompatibility and Manufacturability of Chitosan:PEGDA Hybrid-Gel Scaffolds by Stereolithography.
abstract: Extracellular matrix mimetic hydrogels which hybridize synthetic and natural polymers offer molecularly-tailored, bioactive properties and tunable mechanical strength. In addition, 3D bioprinting by stereolithography allows fabrication of internal pores and defined macroscopic shapes. In this study, we formulated a hybrid biocompatible resin using natural and synthetic polymers (chitosan and polyethylene glycol diacrylate (PEGDA), respectively) by controlling molecular weight of chitosan, feed-ratios, and photo-initiator concentration. Ear-shaped, hybrid scaffolds were fabricated by a stereolithographic method using a 405 nm laser. Hybrid hydrogel scaffolds of chitosan (50-190 kDa) and PEGDA (575 Da) were mixed at varying feed-ratios. Some of the cationic, amino groups of chitosan were neutralized by dialysis in acidic solution containing chitosan in excess of sodium acetate solution to inhibit quenching of newly formed photoradicals. A feed-ratio of 1:7.5 was found to be the most appropriate of the formulations considered in this study in terms of mechanical properties, cell adhesion, and printability. The biofabricated hybrid scaffold showed interconnected, homogeneous pores with a nominal pore size of 50 µm and an elastic modulus of ~400 kPa. Moreover, long-term cell viability and cell spreading was observed via actin filament staining. Printability of the biocompatible resin was confirmed by printing thresholded MR images of an ear and the feed ratio of 1:7.5 provided the most faithful reproduction of the shape. To the best of our knowledge, this is the first report of stereolithographic printing hybridizing cell-adhesive properties of chitosan with mechanical robustness of PEG in scaffolds suitable for repair of complex tissue geometries, such as those of the human ear.
authors.affiliation: Department of Mechanical and Aerospace Engineering, Case Western Reserve University, 10900 Euclid Ave, Cleveland, OH, 44106-7222, USA.
authors.forename: Viola B
authors.initials: VB
authors.lastname: Morris
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, 44106, USA.
authors.forename: Siddharth
authors.initials: S
authors.lastname: Nimbalkar
authors.affiliation: Department of Mechanical and Aerospace Engineering, Case Western Reserve University, 10900 Euclid Ave, Cleveland, OH, 44106-7222, USA.
authors.forename: Mousa
authors.initials: M
authors.lastname: Younesi
authors.affiliation: Department of Mechanical and Aerospace Engineering, Case Western Reserve University, 10900 Euclid Ave, Cleveland, OH, 44106-7222, USA.
authors.forename: Phillip
authors.initials: P
authors.lastname: McClellan
authors.affiliation: Department of Mechanical and Aerospace Engineering, Case Western Reserve University, 10900 Euclid Ave, Cleveland, OH, 44106-7222, USA. oxa@case.edu.|Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, 44106, USA. oxa@case.edu.|Department of Orthopedics, Case Western Reserve University, Cleveland, OH, 44106, USA. oxa@case.edu.
authors.forename: Ozan
authors.initials: O
authors.lastname: Akkus
mesh_terms: D002478:Cells, Cultured; D048271:Chitosan / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D020100:Hydrogels / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008422:Materials Testing; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000737:chemistry / Q000494:pharmacology; D066330:Printing, Three-Dimensional; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D020100:Hydrogels; C437167:poly(ethylene glycol)diacrylate; D011092:Polyethylene Glycols; D048271:Chitosan
keywords: 3D printing; Artificial ear; Aural repair; Biocompatibility; Chitosan; Mechanical Properties; PEGDA; Stereolithography