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Proceeding Paper

A Short Overview of the Formulation of Cellulose-Based Hydrogels and Their Biomedical Applications †

by
Raja Saadan
1,2,
Aziz Ihammi
1,
Mohamed Chigr
1 and
Ahmed Fatimi
2,*
1
Laboratory of Molecular Chemistry, Materials and Catalysis (LCMMC), Faculty of Science and Technology (FSTBM), University Sultan Moulay Slimane (USMS), Mghila Campus, P.O. Box 523, Beni Mellal 23000, Morocco
2
Chemical Science and Engineering Research Team (ERSIC), Department of Chemistry, Polydisciplinary Faculty of Beni Mellal (FPBM), Sultan Moulay Slimane University (USMS), P.O. Box 592 Mghila Campus, Beni Mellal 23000, Morocco
*
Author to whom correspondence should be addressed.
†
Presented at the 1st International Online Conference on Bioengineering (IOCBE 2024), 16–18 October 2024; Available online: https://sciforum.net/event/IOCBE2024/.
Eng. Proc. 2024, 81(1), 3; https://doi.org/10.3390/engproc2024081003
Published: 20 December 2024
Browse Figures
Figure 1
<p>The chemical structure of cellulose—a linear polymer composed of β-D-glucopyranose units covalently linked through (1→4) glycosidic bonds. (Reprinted from Chen et al., 2022 [<a href="#B10-engproc-81-00003" class="html-bibr">10</a>]. Copyright © 2022 MDPI under the terms and conditions of the Creative Commons Attribution license.)</p> "> Figure 2
<p>Some properties of the developed chitosan/HPMC/glycerol hydrogel: (<b>A</b>) photographs of the hydrogel in sol (25 °C) and gel state (32 °C); (<b>B</b>) thermogelation properties; (<b>C</b>) in vitro cytotoxicity results after 48 h incubation. * Significant differences compared to the positive control (<span class="html-italic">p</span> &lt; 0.01). (Reprinted and adapted with permission from Wang et al., 2016 [<a href="#B55-engproc-81-00003" class="html-bibr">55</a>]. Copyright © 2016 Elsevier).</p> "> Figure 3
<p>(<b>A</b>) 3D-bioprinted constructs as a function of CMC/alginate hydrogel formulations; (<b>B</b>) comparison of cell viability in alginate and CMC/alginate hydrogels at different times. * Significant differences between alginate and CMC/alginate (<span class="html-italic">p</span> = 0.05); (<b>C</b>) cell-laden scaffold and filament. (Reprinted and adapted from Habib et al., 2018 [<a href="#B60-engproc-81-00003" class="html-bibr">60</a>]. Copyright © 2018 MDPI under the terms and conditions of the Creative Commons Attribution license).</p> "> Figure 4
<p>(<b>A</b>) Photographs of various NFC/gellan gum hydrogel-based inks with different layer counts following crosslinking; (<b>B</b>) micrographs of morphologies of the different freeze-dried printed structures. Red arrows indicate the presence of pores; (<b>C</b>) cell viability of NFC/gellan gum hydrogel-based inks (dotted line: cell viabilities were all well above the 70% cell viability threshold). * Significant differences compared to the control (<span class="html-italic">p</span> &lt; 0.05).(Reprinted and adapted with permission from Lameirinhas et al., 2023 [<a href="#B61-engproc-81-00003" class="html-bibr">61</a>]. Copyright © 2023 Elsevier).</p> ">
Versions Notes

Abstract

:
Cellulose, the most abundant natural biopolymer, has garnered significant attention for hydrogel development due to its exceptional properties, including biocompatibility, biodegradability, renewability, and mechanical strength. These attributes make cellulose an environmentally friendly and safe material for biomedical engineering applications. Crosslinking is a critical step in hydrogel synthesis, enabling the formation of a 3D network that enhances structural and functional properties. Various crosslinking methods have been employed to tailor cellulose-based hydrogels for specific applications, such as tissue engineering, wound healing, drug delivery, and 3D bioprinting. This paper provides a concise overview of the formulation techniques and biomedical applications of cellulose-based hydrogels. By synthesizing recent advances from the literature, we highlight the unique advantages of cellulose-based hydrogels over other biomaterials and discuss their potential as a sustainable and innovative platform in biomedical engineering.

1. Introduction

Hydrogel-based biomaterials play a fundamental role in developing new solutions to current challenges in biomedical engineering [1]. Hydrogels are three-dimensional (3D) hydrophilic polymer networks that, due to their crosslinked structure, are able to absorb and retain large amounts of water or biological fluids without dissolving [2]. This water-retaining ability gives hydrogels unique properties such as flexibility, softness, and permeability, which closely resemble the properties of living tissue [3]. These characteristics make hydrogels particularly suitable for a wide range of biomedical applications because they combine the structural integrity required for a variety of applications with a high degree of biocompatibility and versatility [4]. These hydrogels can be derived from a variety of sources, including synthetic polymers, natural biopolymers, or a combination of both [5]. Among natural biopolymers, cellulose stands out as a particularly promising material due to its availability, renewability, and excellent properties [6].
Cellulose, the most abundant natural polymer on Earth [7], is a renewable and eco-friendly polysaccharide composed of glucose units linked by β-1,4-glycosidic bonds (Figure 1). Its linear structure, enriched with hydroxyl groups, allows the formation of strong hydrogen bonds, which are key to its exceptional water absorption capacity, mechanical strength, and structural stability [8,9]. The repeating unit of cellulose, cellobiose, provides the molecular basis for these distinctive properties [10].
Known for its biocompatibility and biodegradability, cellulose is readily decomposable by microorganisms, making it a sustainable and non-toxic material suitable for a wide range of applications [11]. It is abundantly available in nature and derived from a wide variety of sources, including plants, specific bacterial strains, and marine organisms. This widespread availability, combined with its remarkable properties, establishes cellulose as a fundamental resource for the development of advanced materials, particularly hydrogels, with promising applications in biomedical fields [10,12].
Despite its remarkable properties, the limitations of cellulose arise from its difficulty in dissolving due to the presence of inter- and intramolecular hydrogen bonds as well as van der Waals forces. However, this limitation can be addressed by chemically modifying cellulose, primarily through the etherification of hydroxyl groups, to produce various cellulose derivatives [13,14].

2. Cellulose Derivatives

Cellulose has one significant limitation: it is poorly soluble in water and most organic solvents [15]. This relates primarily to its highly organized structure, which is maintained by strong intermolecular hydrogen bonds and van der Waals interactions between its linear chains. Chemical methods such as oxidation, etherification, and esterification are proposed for producing water-soluble derivatives with remarkable properties [16]. Etherification, for example, involves the substitution of hydroxyl groups with ether groups. Numerous derivatives were produced by these modifications. These modifications disrupt the crystalline structure, improving solubility in aqueous or organic solvents while maintaining the biocompatibility and biodegradability of cellulose [17].
As presented in Table 1, cellulose derivatives include cellulose dialdehyde (DAC), cellulose dicarboxylic acid (DCC), and 2,2,6,6-tetramethylpiperidine-1-oxyl-oxidized cellulose nanofibrils (TOCNF). Common derivatives such as methylcellulose (MC), ethylcellulose (EC), carboxymethylcellulose (CMC), hydroxypropylcellulose (HPC), hydroxyethylcellulose (HEC), and hydroxypropylmethylcellulose (HPMC) have diverse applications. Other notable forms include nitrocellulose (CN), cellulose acetate (CA), cellulose sulfate (CS), cellulose acetobutyrate (CAB), and hydroxypropylmethylcellulose phthalate (HPMCP) [10]. On the other hand, in chemical synthesis, the copper-catalyzed azide–alkyne cycloaddition is used for reactions like pentynoyl-grafted dialkylated MC. Similarly, thiol–ene click reactions enable the production of amphiphilic cellulose derivatives [18,19].
Thanks to the chemical modifications and/or chemical synthesis, cellulose derivatives enhance the potential uses of cellulose, notably in the development of hydrogels, where their modified chemical structure allows for efficient crosslinking and the construction of strong water-retentive 3D networks [30].

3. Cellulose Hydrogels

3.1. Key Potential Areas of Exploration for Cellulose Hydrogels

Cellulose-based hydrogels have emerged as a groundbreaking material in biomedical and environmental fields, owing to their unique properties such as biocompatibility and rheological characteristics [1,31]. These hydrogels have shown immense promise in diverse biomedical applications. Their ability to form 3D networks with controlled swelling and release mechanisms makes them highly versatile in in vitro and in vivo studies, clinical trials, and innovative biomedical technologies [32]. Table 2 summarizes key studies, clinical trials, and patents, highlighting the progress and potential of cellulose-based hydrogels in various domains. The examples of cellulose-based hydrogels cited in the table include, but are not limited to, applications in cell viability and proliferation, drug release mechanisms, wound healing, tissue engineering, wound dressing efficacy, skin regeneration, drug delivery systems, biodegradability, self-healing properties, and bioink formulation [30,33,34,35,36,37,38,39,40,41,42,43,44].
In vitro studies have explored their role in enhancing cell proliferation, enabling sustained drug release, and accelerating wound healing [33,34,35]. Simultaneously, in vivo studies have demonstrated their effectiveness in regenerating complex tissues and improving wound-healing rates in animal models [30,35]. Ongoing clinical trials aim to translate these findings into practical solutions for treating severe burns, cancer, and chronic wounds [36,37,38]. In this regard, research on various hydrogel formulations using different cellulose derivatives, including CMC and HPMC hydrogels, has demonstrated the clinical efficiency of iontophoresis for delivering a non-steroidal anti-inflammatory drug (celecoxib). HPMC hydrogels showed superior spreadability, enhanced skin retention, and the highest percentage of celecoxib release. Based on these findings, this formulation was deemed optimal for iontophoretic studies. Ex vivo experiments confirmed that iontophoretic drug transport from hydrogels to rat skin was twice as effective as passive diffusion [36]. Similarly, mucoadhesive hydrogels, including HPMC and sodium CMC, have been evaluated for their bioadhesion to the esophagus using an ex vivo rat model and a clinical study on healthy volunteers. The aim was to develop a bioadhesive formulation loaded with hexylaminolevulinate for targeting the esophageal lining. Although HPMC and sodium CMC did not demonstrate the highest esophageal adhesion, Collaud et al. highlighted that sodium CMC-based formulations are promising for the local treatment of esophageal motility disorders, fungal infections, and the delivery of topical anticancer agents to specific esophageal sites [38]. Moreover, as already published in our previous patent-based studies, patents focusing on biodegradable and self-healing cellulose hydrogels reflect the growing emphasis on sustainability and functionality in biomedical engineering [12,45,46,47,48]. These innovations pave the way for integrating cellulose hydrogels with advanced technologies, such as smart drug delivery systems and 3D bioprinting [49,50]. The invention through patent CN103330699B relates to a method for preparing a transdermal drug delivery system using biologically derived cellulose hydrogel as the base material. More specifically, the system comprises three layers: a backing layer, a medicated layer, and a protective layer. The hydrogel slices are soaked, drained, and subsequently bonded to the backing layer on one side and the protective layer on the other, resulting in the final transdermal drug delivery system. The innovative approach utilizes the unique properties of cellulose hydrogel to develop an efficient transdermal delivery platform with enhanced drug absorption capabilities [39]. Likewise, the patented invention by Trexler et al. (US9314531B2) pertains to a method for treating wounds using a re-wet biocompatible cellulose hydrogel membrane, specifically engineered to promote healing in subjects requiring wound care. The hydrogel membrane is a composite material composed of microcrystalline cellulose and bacterial cellulose. It features distinct layering, with bacterial cellulose layers positioned closer to the wound to optimize interaction and healing, while the microcrystalline cellulose layers provide structural support. This invention presents a highly effective and biocompatible solution for wound treatment, combining superior mechanical properties with enhanced wound contact and healing efficiency [40]. On the other hand, the invention claimed by Zhou et al. (CN113150319B) outlines a method for preparing a cellulose nanocrystal-reinforced, high-efficiency, self-healing hydrogel. The invention combines the structural reinforcement of cellulose nanocrystals with the dynamic bonding properties of hyaluronic acid to create a hydrogel with exceptional self-healing efficiency and mechanical robustness [41]. Similarly, the invention claimed by Zhong et al. (CN110804192A) relates to the preparation of an antibacterial bacterial cellulose hydrogel and its method of preparation. The invention demonstrates a method to produce a biocompatible and antibacterial hydrogel using bacterial cellulose and fluorenylmethyloxycarbonyl-modified phenylalanine, which can be used in applications requiring antibacterial properties and biocompatibility [42]. Moreover, the patented invention by Gatenholm et al. (EP3532117B1) relates to a bioink designed for use in 3D bioprinting. The bioink consists of a cellulose nanofibril-based hydrogel that serves as the base material, providing structural integrity and biocompatibility, which are essential for supporting cell growth during the bioprinting process. Calcium-containing particles are also included to support bone regeneration and enhance the bioink’s osteoconductive properties. The formulated bioink composition aims to offer a versatile, biocompatible, and functional material for 3D bioprinting applications, particularly in bone tissue engineering and regenerative medicine [43]. Finally, the patent from Liu et al. (CN110028840A) describes a method for preparing nano-cellulose bioink for 3D bioprinting applications. The process is divided into three key steps, categorized as nanofiber hydrogel preparation, bioactive xyloglucan formation, and bioink formulation. This innovative approach utilizes nano-cellulose and bioactive components to create a biocompatible and functional bioink, enhancing cell adhesion and providing structural integrity for advanced 3D bioprinting applications [44].

3.2. Cellulose-Based Hydrogel Formulation and Applications

Cellulose-based hydrogels may be developed using two methods: physical and chemical crosslinking. Physical crosslinking relies on non-covalent interactions like hydrogen bonding or ionic interactions and avoids toxic agents, making it ideal for biomedical uses. Chemical crosslinking, on the other hand, uses agents such as glutaraldehyde or citric acid to form covalent bonds, resulting in hydrogels with greater mechanical strength and stability. The choice of method depends on the application, balancing biocompatibility, strength, and ease of preparation [15,51].
Cellulose-based composite hydrogels have emerged as promising materials for antibacterial applications [52]. Furthermore, they are considered versatile biomaterials with significant potential in various biomedical applications [10,53], including drug delivery, wound healing, and 3D bioprinting (Table 3).

3.2.1. Drug Delivery Systems

For drug delivery systems, Zhu et al. developed a novel Pickering emulsion delivery system utilizing a complex of CMC and quaternized chitosan (QC) [54]. By protonating and neutralizing CMC prior to complexation, they achieved emulsions with gel-like rheological behavior and exceptional stability against environmental stresses such as pH, salt, temperature, and storage. The encapsulation of curcumin further enhanced emulsion stability and reduced degradation rates, demonstrating the system’s potential as a sustainable and efficient drug delivery platform. Similarly, Wang et al. formulated a thermosensitive hydrogel comprising chitosan, HPMC, and glycerol, which gelates within 15 min at physiological conditions [55]. This hydrogel displayed excellent thermogelation properties, biodegradability, low cytotoxicity, and a controlled protein release profile, making it a promising candidate for biomedical applications (Figure 2).

3.2.2. Wound Healing

In wound healing, Luo et al. introduced a composite hydrogel wound dressing made of aminated hyaluronic acid (aHA) and oxidized HEC, exhibiting optimal gelation time, outstanding swelling capacity (2888%), and remarkable hemocompatibility and biocompatibility, thereby creating an ideal environment for moist wound healing [56]. Furthermore, El Fawal et al. developed HEC hydrogel membranes crosslinked with citric acid and enriched with tungsten oxide [57]. These membranes demonstrated strong anti-inflammatory and antibacterial activities, particularly against Salmonella sp. and Pseudomonas aeruginosa, while maintaining biocompatibility with human dermal fibroblasts and white blood cells. Collectively, these advancements underscore the versatility and potential of cellulose-based hydrogels in addressing critical challenges in biomedical science.

3.2.3. Tissue Engineering

For tissue engineering applications, bacterial cellulose (BC)/collagen composites have been prepared by Saska et al. [58]. The preparation process involves a series of steps that enhance the properties of both biopolymer-based hydrogels for tissue engineering applications. The use of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) facilitates the formation of stable bonds between BC and collagen, enhancing the mechanical properties of the composite. Finally, gamma radiation was employed to sterilize the final product, ensuring that it was safe for medical use. Based on the findings, the incorporation of collagen into BC hydrogels through esterification and subsequent crosslinking results in a composite that exhibits improved mechanical strength and biocompatibility, making it suitable for the target biomedical application—bone tissue engineering. The preparation of CA and chitosan scaffolds for tissue engineering involves a series of steps that enhance their structural and biological properties. As published by Maharjan et al., this process typically includes dissolving chitosan in AcOH, mixing it with CA nanofibers, and subjecting the mixture to freezing and lyophilization, followed by neutralization and washing. The resulting scaffolds exhibit promising characteristics for tissue regeneration [59].

3.2.4. Three-Dimensional Bioprinting

In the field of 3D bioprinting, Habib et al. developed a hybrid hydrogel of sodium alginate and CMC for 3D bioprinting [60]. It demonstrated good printability, shape fidelity, and cell viability, with 86% cell survival after 23 days. This hydrogel shows potential as a biomaterial for 3D bioprinting applications (Figure 3).
Similarly, Lameirinhas et al. developed a hydrogel by concentrating NFC through centrifugation, mixing it with gellan gum, and crosslinking the mixture with calcium chloride [61]. This method resulted in hydrogels with improved rheological and mechanical properties, making them suitable as hydrogel-based bioinks for 3D bioprinting applications (Figure 4).

4. Conclusions

Cellulose-based hydrogels have emerged as a versatile and sustainable platform for various biomedical applications, including tissue engineering, wound healing, and drug delivery systems. Their inherent properties, such as biocompatibility and biodegradability, combined with their adaptability through chemical modifications, have significantly expanded their utility in the biomedical field. Recent advancements in functionalization techniques and derivatizations have enhanced their performance and broadened their scope of applications.
In this study, we have detailed the chemical methods for synthesizing different water-soluble cellulose derivatives, each tailored with specific properties to meet the needs of various biomedical applications. Additionally, we have reviewed key in vitro and in vivo studies, clinical trials, and patents, highlighting the progress made and the significant potential of cellulose-based hydrogels in diverse fields. We also reviewed several examples of cellulose-based hydrogels, which include, but are not limited to, applications in cell viability and proliferation, drug release mechanisms, wound healing, tissue engineering, wound dressing efficacy, skin regeneration, drug delivery systems, biodegradability, self-healing properties, and bioink formulations for 3D bioprinting. These examples demonstrate the broad potential of cellulose-based hydrogels across multiple biomedical sectors.
Looking ahead, future research should prioritize optimizing functionalization methods and improving scalability for large-scale production. Long-term biocompatibility studies will be crucial for facilitating clinical translation. Furthermore, integrating cellulose derivatives with advanced technologies, such as 3D bioprinting and responsive drug delivery systems, offers substantial promise for next-generation biomedical innovations.

Author Contributions

Conceptualization, R.S.; methodology, R.S.; validation, A.I., M.C., and A.F.; formal analysis, R.S.; investigation, R.S., A.I., M.C., and A.F.; data curation, R.S.; writing—original draft preparation, R.S.; writing—review and editing, A.I., M.C., and A.F.; visualization, A.I., M.C., and A.F.; supervision, M.C. and A.F. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

The data presented in this study are available within this manuscript. The following supporting information can be downloaded at: https://sciforum.net/paper/view/19326 (accessed on 15 October 2024), Poster: Saadan, R.; Ihammi, A.; Chigr, M.; and Fatimi, A. Review on the formulation of cellulose-based hydrogels and their biomedical applications. The 1st International Online Conference on Bioengineering (IOCBE 2024), Basel—Switzerland, 16–18 October 2024.

Acknowledgments

The authors acknowledge the academic editor and the chair of the conference for the opportunity to present this work at the 1st International Online Conference on Bioengineering. R.S. gratefully acknowledges the CNRST (Centre National pour la Recherche Scientifique et Technique) in Morocco for the PhD–Associate Scholarship (PASS 2024-2027). Additionally, she acknowledges the French Embassy in Morocco and the CNRST for the grant obtained through the “Doctoral Mobility Program 2024”.

Conflicts of Interest

The authors declare no conflicts of interest.

Abbreviations

3DThree-dimensional
aHAAminated hyaluronic acid
BCBacterial cellulose
CACellulose acetate
CABCellulose acetobutyrate
CMCCarboxymethylcellulose
CNNitrocellulose
CSCellulose sulfate
DACCellulose dialdehyde
DCCCellulose dicarboxylic acid
ECEthylcellulose
EDC1-ethyl-3-(3-dimethylaminopropyl) carbodiimide
HECHydroxyethylcellulose
HPCHydroxypropylcellulose
HPMCHydroxypropylmethylcellulose
HPMCPHydroxypropylmethylcellulose phthalate
MCMethylcellulose
NFCNanofibrillated cellulose
QCQuaternized chitosan
TOCNF2,2,6,6-Tetramethylpiperidine-1-oxyl-oxidized cellulose nanofibrils

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Figure 1. The chemical structure of cellulose—a linear polymer composed of β-D-glucopyranose units covalently linked through (1→4) glycosidic bonds. (Reprinted from Chen et al., 2022 [10]. Copyright © 2022 MDPI under the terms and conditions of the Creative Commons Attribution license.)
Figure 1. The chemical structure of cellulose—a linear polymer composed of β-D-glucopyranose units covalently linked through (1→4) glycosidic bonds. (Reprinted from Chen et al., 2022 [10]. Copyright © 2022 MDPI under the terms and conditions of the Creative Commons Attribution license.)
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Figure 2. Some properties of the developed chitosan/HPMC/glycerol hydrogel: (A) photographs of the hydrogel in sol (25 °C) and gel state (32 °C); (B) thermogelation properties; (C) in vitro cytotoxicity results after 48 h incubation. * Significant differences compared to the positive control (p < 0.01). (Reprinted and adapted with permission from Wang et al., 2016 [55]. Copyright © 2016 Elsevier).
Figure 2. Some properties of the developed chitosan/HPMC/glycerol hydrogel: (A) photographs of the hydrogel in sol (25 °C) and gel state (32 °C); (B) thermogelation properties; (C) in vitro cytotoxicity results after 48 h incubation. * Significant differences compared to the positive control (p < 0.01). (Reprinted and adapted with permission from Wang et al., 2016 [55]. Copyright © 2016 Elsevier).
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Figure 3. (A) 3D-bioprinted constructs as a function of CMC/alginate hydrogel formulations; (B) comparison of cell viability in alginate and CMC/alginate hydrogels at different times. * Significant differences between alginate and CMC/alginate (p = 0.05); (C) cell-laden scaffold and filament. (Reprinted and adapted from Habib et al., 2018 [60]. Copyright © 2018 MDPI under the terms and conditions of the Creative Commons Attribution license).
Figure 3. (A) 3D-bioprinted constructs as a function of CMC/alginate hydrogel formulations; (B) comparison of cell viability in alginate and CMC/alginate hydrogels at different times. * Significant differences between alginate and CMC/alginate (p = 0.05); (C) cell-laden scaffold and filament. (Reprinted and adapted from Habib et al., 2018 [60]. Copyright © 2018 MDPI under the terms and conditions of the Creative Commons Attribution license).
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Figure 4. (A) Photographs of various NFC/gellan gum hydrogel-based inks with different layer counts following crosslinking; (B) micrographs of morphologies of the different freeze-dried printed structures. Red arrows indicate the presence of pores; (C) cell viability of NFC/gellan gum hydrogel-based inks (dotted line: cell viabilities were all well above the 70% cell viability threshold). * Significant differences compared to the control (p < 0.05).(Reprinted and adapted with permission from Lameirinhas et al., 2023 [61]. Copyright © 2023 Elsevier).
Figure 4. (A) Photographs of various NFC/gellan gum hydrogel-based inks with different layer counts following crosslinking; (B) micrographs of morphologies of the different freeze-dried printed structures. Red arrows indicate the presence of pores; (C) cell viability of NFC/gellan gum hydrogel-based inks (dotted line: cell viabilities were all well above the 70% cell viability threshold). * Significant differences compared to the control (p < 0.05).(Reprinted and adapted with permission from Lameirinhas et al., 2023 [61]. Copyright © 2023 Elsevier).
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Table 1. Proposed chemical methods for synthesizing water-soluble derivatives with tailored specific properties.
Table 1. Proposed chemical methods for synthesizing water-soluble derivatives with tailored specific properties.
Chemical MethodCellulose DerivativesRef.
OxidationDAC, DCC, TOCNF[20,21,22]
EtherificationMC, EC, CMC, HPC, HEC, HPMC[23,24,25,26]
EsterificationCN, CA, CS, CAB, HPMCP[13,27,28,29]
Table 2. Overview of key in vitro studies, in vivo studies, clinical trials, and patents on cellulose-based hydrogels.
Table 2. Overview of key in vitro studies, in vivo studies, clinical trials, and patents on cellulose-based hydrogels.
CategoryFocus AreaHighlightsRef.
In vitro studiesCell viability and proliferationCellulose hydrogels enhance fibroblast viability and proliferation.[33]
Drug release mechanismsDemonstrated controlled drug release, suitable for sustained drug delivery systems.[34]
Wound healing applicationsPromote keratinocyte proliferation, aiding in skin regeneration.[35]
In vivo studiesTissue engineeringEffective in regenerating cardiac and neural tissues in animal models.[35]
Wound dressing efficacyImprove wound-healing rates significantly in animal models.[30]
Clinical trialsSkin regenerationTrials assessing cellulose hydrogels for treating severe burns and skin injuries.[36,37]
Drug delivery systemsOngoing trials evaluating cellulose hydrogels for targeted drug delivery.[38]
PatentsBiodegradable hydrogelsPatents filed for cellulose hydrogels in drug delivery and wound care.[39,40]
Self-healing hydrogelsPatent applications for innovations in self-healing cellulose hydrogels for biomedical applications.[41,42]
Hydrogel-based bioinks Patents concerning the formulation of cellulose hydrogel inks for 3D bioprinting based on their ability to form 3D networks with controlled printability.[43,44]
Table 3. Examples of cellulose-based hydrogel formulations with significant potential for various biomedical applications.
Table 3. Examples of cellulose-based hydrogel formulations with significant potential for various biomedical applications.
Biomedical ApplicationsCellulose-Based
Hydrogel Formulation		PreparationRef.
Drug deliveryCMC/QCDissolving anionic CMC in dilute HCl solutions, followed by the addition of QC to form complexes through phase separation and subsequent neutralization.[54]
Chitosan/HPMC/glycerolBlending chitosan and HPMC powders in 0.1 M AcOH, adjusting the pH to 6.8, and adding glycerol to prepare sample solutions.[55]
Wound healing Oxidized HEC/aHAHA-HEC hydrogels were prepared by dissolving aHA and oxidized HEC in NaOH, adding a crosslinker, incubating for 24 h, and soaking in distilled water for neutralization.[56]
HEC/tungsten trioxideHEC hydrogel membranes were prepared by dissolving HEC in water, crosslinking with citric acid, adding WO3, and drying the mixture in Petri dishes.[57]
Tissue engineeringBC/collagenThe BC–collagen composites were prepared by incorporating collagen into BC hydrogels via esterification with Fmoc–glycine, followed by crosslinking with collagen and EDC and drying and sterilization by gamma radiation.[58]
CA nanofibers/chitosanChitosan was dissolved in AcOH, mixed with CA nanofibers, frozen, lyophilized, neutralized with NaOH, washed, and freeze-dried for scaffold preparation.[59]
3D bioprintingCMC/sodium alginate Cellulose hydrogel-based bioinks were prepared by mixing sodium alginate and CMC solutions, followed by a gelation process to form a stable network.[60]
Nanofibrillated cellulose (NFC)/gellan gumHydrogel prepared by concentrating NFC through centrifugation, mixing it with gellan gum, and then crosslinking the mixture with CaCl2.[61]
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Saadan, R.; Ihammi, A.; Chigr, M.; Fatimi, A. A Short Overview of the Formulation of Cellulose-Based Hydrogels and Their Biomedical Applications. Eng. Proc. 2024, 81, 3. https://doi.org/10.3390/engproc2024081003

AMA Style

Saadan R, Ihammi A, Chigr M, Fatimi A. A Short Overview of the Formulation of Cellulose-Based Hydrogels and Their Biomedical Applications. Engineering Proceedings. 2024; 81(1):3. https://doi.org/10.3390/engproc2024081003

Chicago/Turabian Style

Saadan, Raja, Aziz Ihammi, Mohamed Chigr, and Ahmed Fatimi. 2024. "A Short Overview of the Formulation of Cellulose-Based Hydrogels and Their Biomedical Applications" Engineering Proceedings 81, no. 1: 3. https://doi.org/10.3390/engproc2024081003

APA Style

Saadan, R., Ihammi, A., Chigr, M., & Fatimi, A. (2024). A Short Overview of the Formulation of Cellulose-Based Hydrogels and Their Biomedical Applications. Engineering Proceedings, 81(1), 3. https://doi.org/10.3390/engproc2024081003

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