3D Printed Osteoblast–Alginate/Collagen Hydrogels Promote Survival, Proliferation and Mineralization at Low Doses of Strontium Calcium Polyphosphate

Abstract

The generation of biomaterials via 3D printing is an emerging biotechnology with novel methods that seeks to enhance bone regeneration. Alginate and collagen are two commonly used biomaterials for bone tissue engineering and have demonstrated biocompatibility. Strontium (Sr) and Calcium phosphate (CaP) are vital elements of bone and their incorporation in composite materials has shown promising results for skeletal repair. In this study, we investigated strontium calcium polyphosphate (SCPP) doped 3D printed alginate/collagen hydrogels loaded with MC3T3-E1 osteoblasts. These cell-laden scaffolds were crosslinked with different concentrations of 1% SCPP to evaluate the effect of strontium ions on cell behavior and the biomaterial properties of the scaffolds. Through scanning electron microscopy and Raman spectroscopy, we showed that the scaffolds had a granular surface topography with the banding pattern of alginate around 1100 cm−1 and of collagen around 1430 cm−1. Our results revealed that 2 mg/mL of SCPP induced the greatest scaffold degradation after 7 days and least amount of swelling after 24 h. Exposure of osteoblasts to SCPP induced severe cytotoxic effects after 1 mg/mL. pH analysis demonstrated acidity in the presence of SCPP at a pH between 2 and 4 at 0.1, 0.3, 0.5, and 1 mg/mL, which can be buffered with cell culture medium. However, when the SCPP was added to the scaffolds, the overall pH increased indicating intrinsic activity of the scaffold to buffer the SCPP. Moreover, cell viability was observed for up to 21 days in scaffolds with early mineralization at 0.3, 0.5, and 1 mg/mL of SCPP. Overall, low doses of SCPP proved to be a potential additive in biomaterial approaches for bone tissue engineering; however, the cytotoxic effects due to its pH must be monitored closely.

Collagen-Coated Hyperelastic Bone Promotes Osteoblast Adhesion and Proliferation

“…While ceramic-based bone constructs have been used in a large number of studies [46,47], research is still needed to develop scaffolds based on bioresorbable polymers [16]. Previously, we showed that SCPP polymerized alginate/collagen hydrogels facilitate MC-3T3 osteoblast growth and mineralization [48]. However, additional factors such as rigid-ity and essential blood supply are fundamental, especially for bone defects larger than 5 cm [49,50].…”

Calcium Phosphate Biomaterials for 3D Bioprinting in Bone Tissue Engineering

“…Collagen offers additional advantages, such as low immunogenicity and the promotion of bone regeneration. The use of collagen matrices has demonstrated the ability to influence osteoblast behavior within diverse hydrogels [33]. To achieve rapid gelation, self-healing post-bioprinting and subsequent stabilization through secondary crosslinking, shear-thinning, and self-healing properties, alginate was subjected to methacrylation and oxidation and then ionically crosslinked through an egg-shell model [34].…”

The Use of Hydrogels for the Treatment of Bone Osteosarcoma via Localized Drug-Delivery and Tissue Regeneration: A Narrative Review

“…On the contrary, chemical hydrogels are less dependent on external stimuli and have a tendency for greater mechanical resistance [ 46 ]. Finally, the swelling of hydrogels reaches a limit once the cohesive and osmotic forces reach equilibrium [ 47 , 48 ].…”

“…Physically crosslinked hydrogels are assembled without the use of chemical modifications or crosslinking materials [ 49 ]. For example, alginate can be crosslinked using divalent cations within a solution [ 48 ]. However, despite these advantages, physical hydrogels have inconsistent performance in vivo due to their inflexibility towards gel pore size, chemical functionalization, and degradation [ 49 ].…”

“…Most importantly, bioprinters can be loaded with different bioinks containing the biomaterial for fabrication [ 58 ]. A key benefit of this method is the encapsulation of cells within the bioink prior to printing, thus avoiding the variability in cell seeding in post-printed constructs [ 48 ]. Common printing methods include extrusion, inkjet, stereolithography, and laser printing.…”