3D Bioprinting of Hybrid Biopolymer Bioinks for Wound Healing Applications
Date
2025
Authors
Le, Phuong Hien
Editors
Advisors
Losic, Dusan
Tran, Tung
Hassan, Kamrul
Tran, Tung
Hassan, Kamrul
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Thesis
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Abstract
Chronic wounds have become a global epidemic, affecting millions of patients and contributing to high mortality rates. Among the diverse treatment approaches, 3D bioprinting has emerged as a transformative technology, offering unprecedented potential to fabricate biomimetic skin constructs with intricate cellular compositions and develop wound patches enriched with stem cells or bioactive agents to enhance wound healing. Carboxymethyl cellulose (CMC), a water-soluble cellulose derivative, has gained recognition as a promising biomaterial for 3D bioprinting due to its shear-thinning properties, structural stability across varying pH levels, exceptional water absorption capacity, and ability to provide a 3D microenvironment conducive to cellular activities. However, the limited stability of CMC-based constructs necessitates further optimization to unlock its full potential. This thesis introduces and explores several novel hybrid CMC-based bioinks tailored for wound healing applications. First, a multicomponent bioink combining CMC with xanthan gum (XG) and hyaluronic acid (HA) was formulated to harness the printability of CMC and XG alongside the cellular support properties of HA. Ionic crosslinking using ferric ions enhanced the mechanical strength and long-term stability of the printed constructs. The encapsulation of HaCaT cells and human foreskin fibroblasts within the iron-crosslinked bioinks demonstrated excellent cell viability (>95%) and preserved morphology, highlighting the efficacy of this approach in advancing hydrogel-based bioinks for soft tissue engineering. To address critical challenges, including poor electrical conductivity and inadequate antibacterial properties, a second innovation incorporated the conductive polymer poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) into a CMC-alginate (ALG) bioink network. Crosslinking with gallium ions (Ga³⁺) conferred both long-term stability and potent antibacterial properties. The resulting bioinks exhibited excellent rheological properties, biocompatibility, and electroconductivity. Moreover, when combined with electrical stimulation, these bioinks facilitated fibroblast elongation and proliferation, presenting a groundbreaking method to accelerate wound healing. These findings establish hybrid CMC-based bioinks as a versatile platform for advanced wound healing applications, bridging the gap between 3D bioprinting innovations and clinical implementation.
School/Discipline
School of Chemical Engineering
Dissertation Note
Thesis (Ph.D.) -- University of Adelaide, School of Chemical Engineering, 2025
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