Formulation and Characterization of Alginate Dialdehyde, Gelatin, and Platelet-Rich Plasma-Based Bioink for Bioprinting Applications

Abstract

Layer-by-layer additive manufacturing process has evolved into three-dimensional (3D) “bio-printing” as a means of constructing cell-laden functional tissue equivalents. The process typically involves the mixing of cells of interest with an appropriate hydrogel, termed as “bioink”, followed by printing and tissue maturation. An ideal bioink should have adequate mechanical, rheological, and biological features of the target tissues. However, native extracellular matrix (ECM) is made of an intricate milieu of soluble and non-soluble extracellular factors, and mimicking such a composition is challenging. To this end, here we report the formulation of a multi-component bioink composed of gelatin and alginate -based scaffolding material, as well as a platelet-rich plasma (PRP) suspension, which mimics the insoluble and soluble factors of native ECM respectively. Briefly, sodium alginate was subjected to controlled oxidation to yield alginate dialdehyde (ADA), and was mixed with gelatin and PRP in various volume ratios in the presence of borax. The formulation was systematically characterized for its gelation time, swelling, and water uptake, as well as its morphological, chemical, and rheological properties; furthermore, blood- and cytocompatibility were assessed as per ISO 10993 (International Organization for Standardization). Printability, shape fidelity, and cell-laden printing was evaluated using the RegenHU 3D Discovery bioprinter. The results indicated the successful development of ADA–gelatin–PRP based bioink for 3D bioprinting and biofabrication applications.

Natural Hydrogel-Based Bio-Inks for 3D Bioprinting in Tissue Engineering: A Review

“…[46] Platelet-rich plasma encapsulated in alginate-gelatin hydrogel. [101] Agarose hydrogel mixed with human mesenchymal stem cells. [70] Hyaluronic acid a collagen derivative hydrogel containing human bone marrow-derived mesenchymal stromal cells.…”

Review on Multicomponent Hydrogel Bioinks Based on Natural Biomaterials for Bioprinting 3D Liver Tissues

“…In particular, the tendency of gelatin to liquefy at high temperatures (∼37°C) substantially impedes its application in the development of bioink ( Wu et al, 2020 ). Furthermore, gelatin suffers from limitations as a biomaterial for in vitro tissue development because it does not provide any bioactive factors, except for cell-binding motifs ( Somasekharan et al, 2020 ). Hence, to enhance the printability and bioactivity of gelatin, gelatin-based bioinks containing various biomaterials have been developed and employed for bioprinting ( Jang et al, 2018 ; Ashammakhi et al, 2019 ; Bello et al, 2020 ).…”

“…Moreover, the photocrosslinkable hydrogel with ruthenium (Ru)/sodium persulfate (SPS), which can react under visible light conditions, can provide a more cytocompatible environment than those of the other photoinitiators ( Figure 5A ) ( Lim et al, 2016 ). Furthermore, ECM components are added to the gelatin hydrogel to strengthen bioactivity ( Somasekharan et al, 2020 ). Cui et al (2019 ) determined the optimal synthetic conditions for gelatin and methacrylic anhydride suitable for DLP-based 3D bioprinting techniques.…”

De novo Drug Delivery Modalities for Treating Damaged Hearts: Current Challenges and Emerging Solutions

“…Researchers have used naturally occurring alginate that exhibits properties like shear thinning, excellent biocompatibility, and the ability to encapsulate living cells for cardiovascular and wound healing applications. The –OH group present on the alginate is oxidized by using oxidizing agents like sodium peroxide leading to the formation of alginate dialdehyde ( 39 , 40 ). The aldehyde functional groups on alginate have been crosslinked with –NH 2 groups present on gelatin, forming self-crosslinked hydrogels to deliver growth factors and stem cells.…”