Cardiac Tissue Engineering Research Articles

Hydrogels in cardiac tissue engineering: application and challenges.

Cardiovascular disease remains the leading cause of global mortality. Current stem cell therapy and heart transplant therapy have limited long-term stability in cardiac function. Cardiac tissue engineering may be one of the key methods for regenerating damaged myocardial tissue. As an ideal scaffold material, hydrogel has become a viable tissue engineering therapy for the heart. Hydrogel can not only provide mechanical support for infarcted myocardium but also serve as a carrier for various drugs, bioactive factors, and cells to increase myocardial contractility and improve the cell microenvironment in the infarcted area, thereby improving cardiac function. This paper reviews the applications of hydrogels and biomedical mechanisms in cardiac tissue engineering and discusses the challenge of clinical transformation of hydrogel in cardiac tissue engineering, providing new strategies for treating cardiovascular diseases.

Sustained release of heparin from PLLA micropartricles for tissue engineering applications

Heparin holds promise for cardiac tissue engineering, but challenges such as hematoma or bleeding and accumulation in tissue caused by excessive release, and short half-life persist. The present study aimed to introduce a reliable mechanism for the prolonged heparin release from a biocompatible polymer carrier. The designed system must ensure that heparin retains its bioactivity over time while preventing premature release. Heparin was encapsulated within poly (L-lactic acid) microparticles using the double emulsion method, with polyvinyl alcohol employed as the stabilizer. The encapsulation efficiency of heparin in the microparticles was calculated as 25.56 %. The functionality of the design was evaluated using Attenuated Total Reflection Fourier Transform Infrared Spectroscopy, Scanning Electron Microscopy, and Energy Dispersive X-ray Spectroscopy. Drug release and microparticle degradation studies were conducted alongside cell viability tests. The particle sizes ranged from 5 to 10 ± 2.53 μm, with evidence suggesting that heparin promotes the smaller particle formation. The system demonstrated a consistent drug release profile over six weeks with a release rate of 54 % by week two and 97.65 % by week six. The degradation of heparin-loaded microparticles reached less than 50 % by week six, and the loading of heparin did not significantly affect the degradation behavior of the PLLA microparticles in PBS. Furthermore, heparin concentrations between 200 and 400 μg/ml enhanced the viability of Placenta-derived Mesenchymal Stem Cells and H9c2. These findings suggest that the system could be considered as an effective vehicle for sustained heparin delivery across a spectrum of biological applications, particularly in cardiac tissue engineering.

Patterned glycopeptide-based supramolecular hydrogel promotes the alignment and contractility of iPSC-derived cardiomyocytes

The functional restoration of a damaged cardiac tissue relies on a synchronized contractile capacity of exogenous and/or endogenous cardiomyocytes, which is challenging to achieve. Here, we explored the potential of the short glycopeptide diphenylalanine glucosamine-6-sulfate (FFGlcN6S) conjugated with an aromatic moiety, namely fluorenylmethoxycarbonyl (Fmoc), to enhance cardiac tissue regeneration. At physiological conditions, Fmoc-FFGlcN6S assembles into nanofibrous hydrated meshes, i.e., matrix mimicking hydrogels. These hydrogels can be further micropatterned allowing co-existence of hierarchical structures at different lenght. The patterned hydrogels support the culture of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) and promote their alignment. The cultured iPSC-CMs exhibit anisotropic synchronized contractions, indicating maturation and electrical interconnectivity. Moreover, the cultures express specific cardiac markers including, connexin-43 and sarcomeric-α-actinin, confirming enhanced cell-cell crosstalk, spontaneous contractility, and efficient transmission of electrical signals. Our results showcase the potential of short amphiphilic glycopeptides to mimic physical and biochemical cues that are essential for cardiomyocytes functionality and thus, these conjugates can be used in cardiac tissue engineering and regeneration.

Supramolecular Conductive Hydrogels for Tissue Engineering Applications.

Owing to their unique attributes, including reversibility, specificity, directionality, and tunability, supramolecular biomaterials have evolved as an excellent alternative to conventional biomaterials like polymers, ceramics, and metals. Supramolecular hydrogels, in particular, have garnered significant interest because their fibrous architecture, high water content, and interconnected 3D network resemble the extracellular matrix to some extent. Consequently, supramolecular hydrogels have been used to develop biomaterials for tissue engineering. Supramolecular conductive hydrogels combine the advantages of supramolecular soft materials with the electrical properties of metals, making them highly relevant for electrogenic tissue engineering. Given the versatile applications of these hydrogels, it is essential to periodically review high-quality research in this area. In this review, we focus on recent advances in supramolecular conductive hydrogels, particularly their applications in tissue engineering. We discuss the conductive components of these hydrogels and highlight notable reports on their use in cardiac, skin, and neural tissue engineering. Additionally, we outline potential future developments in this field.

3D Nanofiber-Assisted Embedded Extrusion Bioprinting for Oriented Cardiac Tissue Fabrication.

Three-dimensional (3D) bioprinting technology stands out as a promising tissue manufacturing process to control the geometry precisely with cell-loaded bioinks. However, the isotropic culture environment within the bioink and the lack of topographical cues impede the formation of oriented cardiac tissue. To overcome this limitation, we present a novel method named 3D nanofiber-assisted embedded bioprinting (3D-NFEP) to fabricate cardiac tissue with an oriented morphology. Aligned 3D nanofiber scaffolds were fabricated by divergence electrospinning, which provided structural support for printing of the low-viscosity bioink and structural induction to cardiomyocytes. Cells adhered to the aligned fibers after hydrogel degradation, and a high degree of cell alignment was observed. This technology was also demonstrated as a feasible solution for multilayer cell printing. Therefore, 3D-NFEP was demonstrated as a promising method for bioprinting oriented cardiac tissue with low-viscosity bioink and is expected to be applied for structured and cardiac tissue engineering.

Electrohydrodynamic Printing of Microscale Fibrous Scaffolds with a Sinusoidal Structure for Enhancing the Contractility of Cardiomyocytes.

Mimicking the curved collagenous fibers in the cardiac extracellular matrix to fabricate elastic scaffolds in vitro is important for cardiac tissue engineering. Here, we developed sinusoidal polycaprolactone (PCL) fibrous scaffolds with commendable flexibility and elasticity to enhance the contractility of primary cardiomyocytes by employing melt-based electrohydrodynamic (EHD) printing. Microscale sinusoidal PCL fibers with an average diameter of ∼10 μm were printed to mimic the collagenous fibers in the cardiac ECM. The sinusoidal PCL fibrous scaffolds were EHD-printed in a layer-by-layer manner and exhibited outstanding flexibility and elasticity compared with the straight ones. The sinusoidal PCL scaffolds provided an elastic microenvironment for the attaching and spreading of primary cardiomyocytes, which facilitated their synchronous contractive activities. Primary cardiomyocytes also showed improved gene expression and maturation on the sinusoidal PCL scaffolds under electrical stimulation for 5 days. It is envisioned that the proposed flexible fibrous scaffold with biomimetic architecture may serve as a suitable patch for tissue regeneration and repair of damaged hearts after myocardial infarction.

3D-Printable Gelatin Methacrylate-Xanthan Gum Hydrogel Bioink Enabling Human Induced Pluripotent Stem Cell Differentiation into Cardiomyocytes.

We describe the development of a bioink to bioprint human induced pluripotent stem cells (hiPSCs) for possible cardiac tissue engineering using a gelatin methacrylate (GelMA)-based hydrogel. While previous studies have shown that GelMA at a low concentration (5% w/v) allows for the growth of diverse cells, its 3D printability has been found to be limited by its low viscosity. To overcome that drawback, making the hydrogel both compatible with hiPSCs and 3D-printable, we developed an extrudable GelMA-based bioink by adding xanthan gum (XG). The GelMA-XG composite hydrogel had an elastic modulus (~9 kPa) comparable to that of cardiac tissue, and enabled 3D printing with high values of printing accuracy (83%) and printability (0.98). Tests with hiPSCs showed the hydrogel's ability to promote their proliferation within both 2D and 3D cell cultures. The tests also showed that hiPSCs inside hemispheres of the hydrogel were able to differentiate into cardiomyocytes, capable of spontaneous contractions (average frequency of ~0.5 Hz and amplitude of ~2%). Furthermore, bioprinting tests proved the possibility of fabricating 3D constructs of the hiPSC-laden hydrogel, with well-defined line widths (~800 μm).

Internally-crosslinked alginate dialdehyde/alginate/gelatin-based hydrogels as bioprinting inks for prospective cardiac tissue engineering applications

Cardiovascular diseases represent a worldwide social and economic challenge, due to heart tissue limited regenerative capabilities. 3D bioprinted cell-laden constructs are a promising approach to develop patches for cardiac regeneration or in vitro models for new drug preclinical discovery and validation. However, the development of bioinks with optimal mechanical, rheological, and biological properties is still a challenge. Although alginate (Alg)-based bioinks have been extensively explored, such hydrogels lack cell adhesion properties and degradability. Additionally, 3D Alg structures are usually obtained by micro-extrusion bioprinting exploiting conventional external cross-linking methods, which introduce inhomogeneities and unpredictability in construct formation. This work exploits Alg internal ionic gelation mechanism to obtain homogeneous self-standing multilayered 3D printed constructs without employing support baths or post-printing crosslinking treatments, combining an insoluble calcium salt (calcium carbonate, CaCO3) with an acidifying agent (D-(+)-Glucono-1,5-lactone, GDL) to promote controlled release of calcium ions. Alg was blended with oxidized alginate (ADA) and gelatin (Gel) to achieve degradable and cell adhesive hydrogels for cardiac tissue engineering. Firstly, ADA/Alg bioink composition was tailored by varying polymer weight ratio (keeping ADA as the main component) and calcium ions concentration to achieve cardiac tissue-like viscoelastic properties. Then, the amount of Gel in ADA/Alg hydrogels was optimized to support adult human cardiac fibroblasts (AHCFs) adhesion, producing shear thinning inks with tunable viscoelastic properties (G’ 650-1300 Pa) and degradation profile (40-80% weight loss after 21 days in phosphate buffered saline, PBS) by varying Gel concentration. ADA/Alg/Gel hydrogels showed a shear thinning behavior suitable for 3D bioprinting and dependent on ink stabilization time, due to the gradual pH-triggered release of calcium ions over time. AHCFs-laden ADA/Alg/Gel bioinks could be successfully printed producing scaffolds with high shape fidelity and good cell viability post-printing. Finally, 3D AHCF-laden and H9C2-laden ADA/Alg/Gel bioinks with the highest gelatin content (25% w/w) allowed cell adhesion after 24 hours of incubation, showing potential application for cardiac tissue modelling. This research presented a comprehensive framework for advancing the design of bioink formulations enabling the printing of cell-adhesive and self-supporting constructs.

Research progress of electrospinning polyurethane fiber in the field of biomedical tissue engineering

Polyurethane materials have good biocompatibility, blood compatibility, mechanical properties, fatigue resistance and processability, and have always been highly valued as medical materials. Polyurethane fibers prepared by electrostatic spinning technology can better mimic the structure of natural extracellular matrices (ECMs), and seed cells can adhere and proliferate better to meet the requirements of tissue repair and reconstruction. The purpose of this review is to present the research progress of electrostatically spun polyurethane fibers in bone tissue engineering, skin tissue engineering, neural tissue engineering, vascular tissue engineering and cardiac tissue engineering, so that researchers can understand the practical applications of electrostatically spun polyurethane fibers in tissue engineering and regenerative medicine.

Simultaneous electro-dynamic stimulation accelerates maturation of engineered cardiac tissues generated by human iPS cells

Electrical and dynamic stimulation are commonly employed to enhance the maturation of engineered cardiac tissue (ECT) derived from human induced pluripotent stem cells (iPSCs), reflecting the physiological environment of the heart. While electrical stimulation mimics natural bioelectrical signals and dynamic stimulation replicates mechanical forces, the combined effects of these stimuli on ECT maturation have not been thoroughly explored. We hypothesized that simultaneous electro-dynamic stimulation would enhance ECT maturation and function more effectively than either stimulus alone. Human iPSC-derived cardiovascular cells were co-cultured with Collagen I and Matrigel for 2 weeks, followed by a comparative analysis of four groups: no stimulation, dynamic stimulation, electrical stimulation, and simultaneous electro-dynamic stimulation. The functionality of ECTs was assessed by measuring contractile capacity and calcium indicators, and histological assessments examined structural maturation. Our results demonstrated that simultaneous electro-dynamic stimulation significantly increased the CM component, elevated TNNT2 mRNA expression levels, and enhanced calcium transient capacity. Additionally, ECTs subjected to simultaneous stimulation exhibited a positive force-frequency relationship in contractility and an elevation in peak calcium flux, indicative of advanced tissue maturation. Moreover, simultaneous stimulation promoted vascular network formation within the ECTs, suggesting improved structural organization. These findings underscore the importance of simultaneous stimulation for developing effective cardiac tissue engineering strategies.

Latest progress of self-healing hydrogels in cardiac tissue engineering.

Cardiovascular diseases represent a significant public health challenge and are responsible for more than 4million deaths annually in Europe alone (45% of all deaths). Among these, coronary-related heart diseases are a leading cause of mortality, accounting for 20% of all deaths. Cardiac tissue engineering has emerged as a promising strategy to address the limitations encountered after myocardial infarction. This approach aims to improve regulation of the inflammatory and cell proliferation phases, thereby reducing scar tissue formation and restoring cardiac function. In cardiac tissue engineering, biomaterials serve as hosts for cells and therapeutics, supporting cardiac restoration by mimicking the native cardiac environment. Various bioengineered systems, such as 3D scaffolds, injectable hydrogels, and patches play crucial roles in cardiac tissue repair. In this context, self-healing hydrogels are particularly suitable substitutes, as they can restore structural integrity when damaged. This structural healing represents a paradigm shift in therapeutic interventions, offering a more native-like environment compared to static, non-healable hydrogels. Herein, we sharply review the most recent advances in self-healing hydrogels in cardiac tissue engineering and their potential to transform cardiovascular healthcare.

Development of a high-speed imaging system for real time evaluation and monitoring of cardiac engineered tissues.

Stem cell derived cardiac monolayers have high potential for tissue regeneration, in vitro drug testing and disease modeling. However, current differentiation protocols are still sub-optimal, resulting in cultures with variable yields and properties. We propose a high-speed lenseless imaging system, integrated with an electrical stimulation unit, to optimize the generation of these cultures. This tool relies on the variations of cellular patterns, during contraction, measured by digital imaging. The imaging system can monitor cardiac cell sheet function and structure, providing the necessary tools to quickly evaluate engineered monolayer. It can record high speed videos and capture high resolution images, from which tissue spatial organization and contractile characteristics can be obtained. Validation of the system was performed using cardiomyocytes derived from human induced pluripotent stem cell and neonatal rat cardiomyocytes. The imaging system allows the observation, acquisition and analysis of important data relating to contractile activity development of cardiac cells, making it a promising tool for optimization in cardiac tissue engineering.

Macrophages: A missing key in cardiac tissue engineering for sustained vascularization

Macrophages regulate angiogenesis, repair, conduction, and homeostasis in heart tissue. Landau etal.1 demonstrate that incorporating primitive macrophages into engineered heart tissues significantly promotes long-term vascularization and cardiac maturation. This advance demonstrates the importance of resident immune-vascular microenvironments in cardiac tissue engineering, marking an important step forward for heart-on-chip technologies.

Graphene-enhanced PCL electrospun nanofiber scaffolds for cardiac tissue engineering.

Cardiovascular diseases, particularly myocardial infarction, have significant healthcare challenges due to the limited regenerative capacity of injured heart tissue. Cardiac tissue engineering (CTE) offers a promising approach to repairing myocardial damage using biomaterials that mimic the heart's extracellular matrix. This study investigates the potential of graphene nanopowder (Gnp)-enhanced polycaprolactone (PCL) scaffolds fabricated via electrospinning to improve the properties necessary for effective cardiac repair. This work aimed to analyze scaffolds with varying graphene concentrations (0.5%, 1%, 1.5%, and 2% by weight) to determine their morphological, chemical, mechanical, and biocompatibility characteristics. The results presented that incorporating graphene improves PCL scaffolds' mechanical properties and cellular interactions. The optimal concentration of 1% graphene significantly enhanced mechanical properties and biocompatibility, promoting cell adhesion and proliferation. These findings suggest that Gnp-enhanced PCL scaffolds at this concentration can serve as a potent substrate for CTE providing insights into designing more effective biomaterials for myocardial restoration.

Comparative Analysis of Decellularization Methods on Bovine Pericardium Scaffolds for Cardiac Tissue Engineering

Background: Congenital heart disease (CHD) involves structural heart abnormalities present since fetal development. Corrective surgery is often the ideal treatment, utilizing implants or scaffolds for tissue repair. However, repeated surgeries may be required due to declining function of grafts, leading to increased healthcare costs. Bovine pericardium is a promising scaffold material for tissue engineering due to its composition of collagen, glycosaminoglycans (GAGs), and proteoglycans. This study aimed to compare the effectiveness of bovine pericardium scaffolds using different decellularization methods: sodium dodecyl sulfate (SDS) and hydrogen peroxide (H2O2). Methods: An experimental study was conducted with bovine pericardium scaffolds divided into control and treatment groups. The treatment groups used decellularization with SDS (0.5%, 1%) and H2O2 (3%). Scaffolds were evaluated for tensile strength, strain, Young's modulus, and histological properties, including nuclear density, collagen density, and GAG content. Data were analyzed using statistical methods to compare the effectiveness of each decellularization technique. Results: Histological analysis revealed that all decellularized samples showed no nuclear density, while control samples displayed light nuclear density. Collagen density was light in scaffolds treated with SDS 0.5% and H2O2, while SDS 1% resulted in no collagen presence. GAG density was absent in SDS-treated samples and minimal in H2O2-treated samples. Tensile strength was highest in H2O2-treated scaffolds (24.01 N) and lowest in SDS 0.5%. SDS 1% showed the greatest tensile strain, while H2O2-treated scaffolds had the highest stiffness. Conclusion: The decellularization methods effectively removed cellular components from the bovine pericardium scaffolds, with varying impacts on the extracellular matrix. SDS 1% provided the most elastic scaffold, while H2O2 preserved tensile strength and stiffness. These findings suggest that the choice of decellularization method can be optimized based on the desired mechanical properties of the scaffold for cardiac tissue engineering applications. Further research is needed to evaluate the long-term performance of these scaffolds in clinical settings.

Research Progress on Cardiac Tissue Construction of Mesenchymal Stem Cells for Myocardial Infarction.

Heart failure is still the main complication affecting the prognosis of acute myocardial infarction (AMI), and mesenchymal stem cells (MSCs) are an effective treatment to replace necrotic myocardium and improve cardiac functioning. However, the transplant survival rate of MSCs still presents challenges. In this review, the biological characteristics of MSCs, the progress of mechanism research in the treatment of myocardial infarction, and the advances in improving the transplant survival rate of MSCs in the replacement of necrotic myocardial infarction are systematically described. From a basic to advanced clinical research, MSC transplants have evolved from a pure injection, an exosome injection, the genetic modification of MSCs prior to injection to the cardiac tissue engineering of MSC patch grafting. This study shows that MSCs have wide clinical applications in the treatment of AMI, suggesting improved myocardial tissue creation. A broader clinical application prospect will be explored and developed to improve the survival rate of MSC transplants and myocardial vascularization.

Recent Advances in Biomacromolecule‐Reinforced 2D Material (2DM) Hydrogels: From Interactions, Synthesis, and Functionalization to Biomedical Applications

AbstractRegenerative biomedicine has emerged as a forefront area in medical research, heralding a new era of therapeutic strategies. This review delineates the integration of 2D materials (2DMs) within the area of biomedical engineering, leveraging their superior physicochemical attributes for enhance biomedical outcomes. The synergistic interaction between biomacromolecules and 2DMs is explored, demonstrating their potential to mitigate the limitations inherent to each while simultaneously augmenting their beneficial properties. In particular, incorporating 2DMs into hydrogels highlights their capability to enhance the mechanical strength of hydrogels, providing a biomimetic scaffold for tissue engineering regeneration and cancer diagnosis and therapy. An overview of the synthetic methodologies are provided for 2DMs, elucidating their interaction dynamics with biomacromolecules. The review primarily concentrates on the applications of biomacromolecule‐reinforced 2DM hydrogels across various biomedical fields, including bone tissue engineering, wound healing, neural tissue engineering, cardiac tissue engineering, as well as in the delivery of drugs and genes, cancer therapy, and biosensing technologies. Finally, the review discusses the existing challenges and future outlook for developing and using biomacromolecule‐reinforced 2DM hydrogels, underlining their transformative potential in regenerative medicine.

Cardiac Tissue Engineering: A Journey from Scaffold Fabrication to In Vitro Characterization

Cardiac tissue engineering has been rapidly evolving with diverse applications, ranging from the repair of fibrotic tissue caused by “adverse remodeling,” to the replacement of specific segments of heart tissue, and ultimately to the creation of a whole heart. The repair or replacement of cardiac tissue often involves the development of tissue scaffolds or constructs and the subsequent assessment of their performance and functionality. For this, the design and/or selection of biomaterials, and cell types, scaffold fabrication, and in vitro characterizations are the first starting points, yet critical, to ensure success in subsequent implantation in vivo. This highlights the importance of scaffold fabrication and in vitro experiments/characterization with protocols for cardiac tissue engineering. Yet, a comprehensive and critical review of these has not been established and documented. As inspired, herein, the latest development and advances in scaffold fabrication and in vitro characterization for cardiac tissue engineering are critically reviewed, with focus on biomaterials, cell types, additive manufacturing techniques for scaffold fabrication, and common in vitro characterization techniques or methods. This article would be of benefit to the ones who are working on cardiac tissue engineering by providing insights into the scaffold fabrication and in vitro investigations.

Fabrication of chitin-fibrin hydrogels to construct the 3D artificial extracellular matrix scaffold for vascular regeneration and cardiac tissue engineering.

As the cornerstone of tissue engineering and regeneration medicine research, developing a cost-effective and bionic extracellular matrix (ECM) that can precisely modulate cellular behavior and form functional tissue remains challenging. An artificial ECM combining polysaccharides and fibrillar proteins to mimic the structure and composition of natural ECM provides a promising solution for cardiac tissue regeneration. In this study, we developed a bionic hydrogel scaffold by combining a quaternized β-chitin derivative (QC) and fibrin-matrigel (FM) in different ratios to mimic a natural ECM. We evaluated the stiffness of those composite hydrogels with different mixing ratios and their effects on the growth of human umbilical vein endothelial cells (HUVECs). The optimal hydrogels, QCFM1 hydrogels were further applied to load HUVECs into nude mice for in vivo angiogenesis. Besides, we encapsulated human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) into QCFM hydrogels and employed 3D bioprinting to achieve batch fabrication of human-engineered heart tissue (hEHT). Finally, the myocardial structure and electrophysiological function of hEHT were evaluated by immunofluorescence and optical mapping. Designed artificial ECM has a tunable modulus (220-1380 Pa), which determines the different cellular behavior of HUVECs when encapsulated in these. QCFM1 composite hydrogels with optimal stiffness (800 Pa) and porous architecture were finally identified, which could adapt for in vitro cell spreading and in vivo angiogenesis of HUVECs. Moreover, QCFM1 hydrogels were applied in 3D bioprinting successfully to achieve batch fabrication of both ring-shaped and patch-shaped hEHT. These QCFM1 hydrogels-based hEHTs possess organized sarcomeres and advanced function characteristics comparable to reported hEHTs. The chitin-derived hydrogels are first used for cardiac tissue engineering and achieve the batch fabrication of functionalized artificial myocardium. Specifically, these novel QCFM1 hydrogels provided a reliable and economical choice serving as ideal ECM for application in tissue engineering and regeneration medicine.

Decellularization of macroalgae Eucheuma cottonii: A potential cellulose-based biomaterial for tissue engineering

Introduction: The success of tissue engineering depends on the characteristics of three-dimensional (3D) scaffolds, such as mechanical strength, porosity, and biocompatibility. These scaffolds are essential both in vitro and in vivo, as they better replicate the natural extracellular matrix (ECM). Cellulose, abundant in nature, is a prime candidate due to its biocompatibility, adaptable biomechanical properties, and cost-effectiveness. It has been explored for applications for cardiac, cartilage, and bone tissue engineering. This study aimed at the macroscopic and microscopic characteristics of decellularized Eucheuma cottonii using SDS (sodium dodecyl sulfate) to assess its potential as a tissue engineering scaffold. Methods: Macroalgae Eucheuma cottonii were cut into small pieces and then immersed in three different concentrations of SDS solution, namely 0.1%, 0.5%, and 1%. The samples were then agitated using a rotary shaker at 160 RPM for four days. The decellularized macroalgae were processed histologically and stained with Hematoxyline-eosin (H&E). In addition, microscopic characterizations were also assessed via Scanning Electron Microscope (SEM) analysis. Results: The results indicated the absence of nuclei or cellular contents with intact ECM, confirming acellular microarchitecture, in the decellularized Eucheuma cottoni with 1% SDS. Remarkably, SEM analysis also revealed the porous structure of decellularized Eucheuma cottonii with pore sizes ranging from 5 to 30 μm. Conclusion: This preliminary study demonstrated the potential of decellularized macroalgae as alternative nature scaffolds. Decellularized Eucheuma cottonii tissues are expected to be cellulose-based biomaterials for candidate biomedical applications in vitro and in vivo in future studies.