3D Printing of Gelatine/Alginate/β‐Tricalcium Phosphate Composite Constructs for Bone Tissue Engineering

Abstract

Bone tissue engineering studies have brought three‐dimensional scaffolds into focus that can provide tissue regeneration with designed porosity and strengthened structure. Current research has concentrated on the fabrication of natural and synthetic polymer‐based complex structures that closely mimic biological tissues due to their superior biocompatibility and biodegradabilities. Gelatine/Sodium Alginate hydrogels reinforced with different concentrations of β‐Tricalcium Phosphate (TCP) (10, 13, and 15 wt.%) were studied to form 3D bone tissue. Physical, mechanical, chemical, morphological properties and biodegradability of the constructs were investigated. Furthermore, in vitro biological assay with human osteosarcoma cell line (SAOS‐2) was performed to determine the biocompatibility of the constructs. It is found that cell viability rates for all constructs were increased and maximum cell viability rate was attained for 20%Gelatine/2%Alginate/10%TCP (wt.). The present work demonstrates that 3D printed Gelatine/Alginate/TCP constructs with porous structures are potential candidates for bone tissue engineering applications.

An Overview of Extracellular Matrix-Based Bioinks for 3D Bioprinting

“…Therefore, alginate can provide a cytoprotective effect against processing pressure stress. Kalkandelen et al (2019) investigated gelatine/sodium alginate hydrogels reinforced with β-Tricalcium Phosphate to form 3D bone tissue. In vitro bioassays with a human osteosarcoma cell line, SAOS-2, were performed to determine the biocompatibility of the constructs.…”

“… Nelson et al (2021) use silica-gelatin hybrid ink to produced 3D grid-like scaffolds using a coupling agent, (3-glycidyloxypropyl)trimethoxysilane, to form covalent bonds between the silicate and gelatin co-networks, which improved the mechanical properties of the scaffold. In addition, tricalcium phosphate ( Kalkandelen et al, 2019 ), metal nanoparticles ( Zhu et al, 2017 ), bioceramic materials ( Diloksumpan et al, 2020 ), and others have been added to biomaterials to improve the mechanical, chemical, and electrical properties of inks.…”

Development of 3D Bioactive Scaffolds through 3D Printing Using Wollastonite–Gelatin Inks

“…The possibility to control porosity and interconnectivity provides a valuable tool to enhance cell-biomaterial or tissue-specific interactions, including the access and distribution of cells into the scaffold core, and to improve the transportation of nutrients and oxygen [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ]. Currently, the main strategies in bone tissue engineering are focused on the development of 3D printed scaffolds based on biomimetic composites, with high precision and reproducibility [ 3 , 6 , 8 , 9 , 10 , 11 ]. The extracellular matrix (ECM) of bone is a natural composite consisting of hydroxyapatite (inorganic phase) and type I collagen (main organic component) [ 10 , 11 , 12 ].…”

“…Hydrogel precursors were widely used in ink formulations due to their printability and easy crosslinking, ensuring the stability and integrity of the printed structures [ 11 , 16 ]. Gelatin, a naturally derived biopolymer from collagen, has been extensively proposed due to its arginine–glycine–aspartic acid (RGD) sequence, biocompatibility, biodegradability, and variety from multiple sources [ 8 , 12 , 14 , 17 , 18 ]. While ink formulations are typically prepared with mammalian gelatins, religious issues or the risk of bovine spongiform encephalopathy transmitting may bring to attention the use of other types of gelatin [ 19 , 20 , 21 ].…”

“…The main combination of biomaterials for composite scaffolds fabrication as bone tissue mimics was based on calcium phosphates as an inorganic component and hydrogels precursors as organic phase [ 3 , 12 , 17 ]. Hydroxyapatite, β-tricalcium phosphate or a combination of them, were broadly used to produce 3D printed composites due to their intrinsic bioactivity and osteoconductivity [ 2 , 3 , 6 , 8 , 9 , 10 , 12 , 17 , 22 , 24 ]. Apart from those, calcium silicates are another important bioceramic class which have gained considerable attention due to their outstanding bioactivity for biomimetic surface mineralization [ 22 , 23 , 24 , 25 , 26 ].…”