Development of a novel alginate‐polyvinyl alcohol‐hydroxyapatite hydrogel for 3D bioprinting bone tissue engineered scaffolds

Abstract

Three-dimensional printed biomaterials used as personalized tissue substitutes have the ability to promote and enhance regeneration in areas of defected tissue. The challenge with 3D printing for bone tissue engineering remains the selection of a material with optimal rheological properties for printing in addition to biocompatibility and capacity for uniform cell incorporation. Hydrogel biomaterials may provide sufficient printability to allow cell encapsulation and bioprinting of scaffolds with uniform cell distribution. In this study, a novel alginate-polyvinyl alcohol (PVA)-hydroxyapatite (HA) hydrogel formulation with optimal rheological properties for 3D bioprinting of mouse calvaria 3T3-E1 (MC3T3) cells into scaffolds of high shape fidelity has been developed. A systematic investigation was conducted to determine the effect of varying concentrations of alginate, phosphate, calcium, and the PVA-HA suspension in the formulation on the resulting viscosity and thus printability of the hydrogel. HA, the main mineral component in natural bone, was incorporated into the hydrogel formulation to create a favorable bone-forming environment due to its excellent osteoconductivity. Degradation studies in α-MEM cell culture media showed that the 3D printed alginate-PVA-HA scaffolds remained in-tact for 14 days. MC3T3 cells were well distributed and encapsulated throughout the optimal hydrogel formulation and expressed high viability through the completion of the 3D printing process. Thus, the development of this novel, osteoconductive, biodegradable, alginate-PVA-HA formulation and its ability to 3D bioprint tissue engineered scaffolds make it a promising candidate for treating personalized bone defects. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1457-1468, 2017.

Interaction of fibroblasts and induced pluripotent stem cells with poly(vinyl alcohol)‐based hydrogel substrates

“…Although its hydrophilic nature shows several advantages for cell culture, it is also challenging to avoid rapid dissolution of PVA‐based materials in aqueous media while maintaining suitable culture conditions. Water‐resistant alternatives described in the literature include blends made of PVA and natural polymers (e.g., chitosan, alginate, and gelatin; Bendtsen, Quinnell, & Wei, ; Khorasani et al, ; Rodríguez‐Rodríguez et al, ), or PVA hydrogels obtained from freeze/thaw cycles (Chee, de Goetten Lima, Devine, & Nugent, ; Khorasani et al, ; Liu et al, ; Rodríguez‐Rodríguez et al, ), which result in physical cross‐linking between the polymer chains. Other alternatives include chemical cross‐linking with glutaraldehyde, and acrylates (Morandim‐Giannetti et al, ; Ossipov, Piskounova, & Hilborn, ).…”

In vitro evaluation of 3D bioprinted tri‐polymer network scaffolds for bone tissue regeneration

“…The incorporation of collagen did not significantly affect the viscosity and thus printability of the hydrogel formulation. In order for a scaffold of high shape fidelity to be printed, it is of the most importance that the hydrogel be continuously extruded and not too viscous to clog the needle . Also, it must not negatively impact the capability of the formulation to protect the encapsulated cells throughout the printing process and shield them from the shear stresses applied during extrusion .…”

“…Thus, in this work, we initially evaluated the ability of our previously developed novel alginate‐polyvinyl alcohol (PVA)‐HA hydrogel formulation and to support cellular life and functions in in vitro culture . We have 3D printed pre‐osteoblastic MC3T3 cells into scaffolds for bone tissue regeneration and assessed the proliferation of these cells encapsulated within the scaffolds.…”

Advances in three‐dimensional bioprinting of bone: Progress and challenges

“…Among the existing state‐of‐the‐art techniques, rapid prototyping technology or 3D printing combined with computer‐aided design (CAD) and computer‐aided manufacturing (CAM) is the most effective strategy for replicating the complex bone anatomy for developing patient‐specific grafts (Melchels et al, ). It utilizes patient data obtained via computerized axial tomography scan or magnetic resonance imaging, as a guide map to fabricate an identical scaffold that matches with the patient's defect parameters (Bendtsen, Quinnell, & Wei, ). This allows fabrication of scaffolds for complex defects, which are seeded with cells (or co‐printed with cells in the case of bioprinting) for subsequent tissue engineering applications (Bendtsen et al, ; Das et al, ).…”

“…It utilizes patient data obtained via computerized axial tomography scan or magnetic resonance imaging, as a guide map to fabricate an identical scaffold that matches with the patient's defect parameters (Bendtsen, Quinnell, & Wei, ). This allows fabrication of scaffolds for complex defects, which are seeded with cells (or co‐printed with cells in the case of bioprinting) for subsequent tissue engineering applications (Bendtsen et al, ; Das et al, ). An alternative method utilizes a negative mould or the complementary design of the desirable scaffold, which acts as a sacrificial template, wherein the final scaffold is cast and procured (Jia et al, ).…”