Smart Theranostic Platforms Based on Carbohydrate Hydrogels

Abstract

Carbohydrate-based hydrogels represent a new advancement in the development of multifunctional biomedical systems, thanks to their intrinsic biocompatibility, structural versatility, and capacity for functional modification. This review examines the latest progress made in employing these materials as intelligent theranostic platforms, with a particular focus on their role as biosensors and therapeutic drug delivery devices. Engineered to interact dynamically with the biological environment, carbohydrate hydrogels enable the site-specific release of therapeutic agents while simultaneously supporting the monitoring of key physiological markers. Their dual functionality offers significant advantages in managing complex pathologies such as cancer, metabolic disorders, and chronic inflammation, where personalized treatment and real-time feedback are essential. By exploring their biological application, this review underscores the pivotal role played by carbohydrate hydrogels in advanced therapeutic technologies.

1. Introduction

The rapid evolution of medical technologies has reshaped modern healthcare, introducing sophisticated tools that significantly enhance diagnostics, treatment, and patient monitoring. Among these innovations, biosensors have emerged as critical instruments, combining biological sensing elements with advanced signal transducers to monitor a variety of physiological and biochemical parameters [1]. Their accuracy, non-invasive operation, and rapid feedback have positioned them as essential tools across numerous biomedical applications [2]. A particularly promising class is that of hydrogel-based biosensors. Hydrogels—three-dimensional polymeric networks with a high affinity for water—have attracted growing interest due to their tunable properties, soft tissue-like consistency, and excellent biocompatibility [3]. These attributes are particularly advantageous for developing wearable or implantable biosensing platforms. Moreover, their inherent sensitivity to environmental stimuli such as pH, temperature, or the presence of specific analytes enables their functionality in dynamically changing biological settings [3]. Notably, carbohydrate-based hydrogels, synthesized from naturally derived polysaccharides and oligosaccharides, offer additional benefits including biodegradability, reduced immunogenicity, and abundant functional groups for chemical modification, making them ideal candidates for intelligent theranostic systems. Carbohydrate hydrogels, indeed, are effective from the continuous monitoring of glucose levels in diabetic patients to the real-time detection of cancer biomarkers and their integration into bio-electrochemical devices [4]. Simultaneously, the utility of carbohydrate-based hydrogels extends into their function as responsive drug delivery vehicles [5]. Their structural versatility allows for the encapsulation and controlled release of therapeutic agents, with delivery triggered by specific physiological cues. These intelligent hydrogel systems can be engineered to release drugs in response to changes in local pH, temperature, or enzymatic activity, thereby achieving targeted and site-specific treatment [6]. This allows for site-specific, time-sensitive, and personalized treatment, reducing side effects and improving therapeutic outcomes. For example, pH-responsive carbohydrate hydrogels can be programmed to release anti-inflammatory agents in inflamed tissues, while thermoresponsive formulations provide the controlled delivery of chemotherapeutics or analgesics, particularly useful in oncology and postoperative care. Furthermore, these hydrogels enhance the bioavailability of poorly soluble compounds and stabilize delicate biomolecules such as proteins and nucleic acids, thereby expanding their applicability to advanced therapeutic domains including gene therapy and regenerative medicine. This dual functionality is at the heart of smart theranostics—a combined approach to therapy (thera-) and diagnostics (-nostics). For example, a hydrogel can be designed to detect an abnormal pH in a tissue (diagnosis) and simultaneously release a drug in response to that change (therapy). While several reviews have examined the general biomedical applications of carbohydrate-based hydrogels, few have explored their role in integrated theranostic platforms that simultaneously perform biosensing and drug delivery functions. To the best of our knowledge, no previous review has provided a detailed analysis of these dual-functional systems with a focus on their structural versatility, stimuli-responsiveness, and clinical applicability. This review aims to fill this gap by offering a comprehensive and interdisciplinary perspective that connects material science, clinical innovation, and biomedical engineering with the aim of contributing to a more responsive, sustainable, and patient-centered healthcare future. The following flowchart helps to fully understand the text.

[Natural Carbohydrate Sources]
(e.g., chitosan, alginate, and dextran)
[Synthesis of Hydrogels]
- 3D polymeric network;
- Biocompatible, biodegradable;
- Modifiable functional groups.
[Hydrogel Properties]
- Tunable porosity;
- High water content;
- Stimuli-responsiveness (pH, T°, and enzymes).
[Integrated Theranostic Functions]
BIOSENSING	DRUG DELIVERY
- Glucose monitoring;	- Targeted release;
- Cancer biomarkers;	- Site-specific action;
- Respiratory markers.	- pH-/T°-/enzyme-triggered.
[Clinical Applications]
- Cardiac health monitoring;
- Respiratory diagnostics;
- Controlled drug administration;
- Oncology and postoperative care;
- Gene therapy and regenerative medicine.

2. Carbohydrate-Based Hydrogels

Carbohydrate-based hydrogels are three-dimensional, hydrophilic polymer networks derived from natural polysaccharides capable of absorbing and retaining significant amounts of water while preserving their structural integrity. Owing to their origin from renewable resources such as cellulose, chitosan, alginate, starch, or dextran, these hydrogels offer exceptional biocompatibility and biodegradability, making them particularly attractive for biomedical and technological applications [6]. Their high water content and extracellular matrix (ECM)-like structure facilitate integration into biological environments with minimal immune reaction, enhancing their use in therapeutic and diagnostic systems [7]. Because of these favorable attributes, carbohydrate-based hydrogels have become vital platforms for biosensor development and targeted drug delivery, especially where compatibility with tissues and bodily fluids is crucial. Their mechanical properties can be finely tuned through crosslinking or blending techniques, resulting in hydrogels that range from soft and flexible to mechanically robust, suitable for use in skin-contact sensors, injectable implants, or tissue engineering scaffolds. A distinct advantage of carbohydrate-derived hydrogels lies in their natural affinity for aqueous environments and their intrinsic responsiveness to physiological stimuli. These features enable their use in sensing applications that require precise environmental feedback, such as glucose monitoring or the detection of metabolites like lactate and urea [7]. Furthermore, carbohydrate-based hydrogels offer an ideal matrix for immobilizing bioactive molecules, including enzymes, antibodies, nucleic acids, or even whole cells, while preserving their biological function. For example, glucose oxidase has been effectively incorporated into chitosan or alginate hydrogels for real-time glucose monitoring in diabetic patients. Similarly, these materials have been employed to develop immunosensors for cancer detection or environmental monitoring thanks to their capacity to provide a protective and hydrated environment [8]. Carbohydrate-based hydrogels also exhibit excellent stimuli-responsive behavior, altering their swelling capacity, morphology, optical transparency, or even electrical conductivity in response to external cues. pH-sensitive polysaccharide hydrogels, for instance, can swell in acidic environments, making them valuable in identifying cancerous tissues, which typically exhibit lower pH levels. Thermoresponsive carbohydrate-based hydrogels are also being explored for their ability to respond to physiological temperature changes, supporting applications in thermal diagnostics or smart drug release systems. Light- or enzyme-responsive formulations further extend their use into more advanced biosensing and biomedical domains [6]. In addition, a particularly promising area for carbohydrate-based hydrogels is in the field of drug delivery. Their biocompatibility and capacity to encapsulate and gradually release a range of therapeutic molecules—such as small drugs, peptides, proteins, and genetic material—make them ideal for targeted therapies. The controlled release can occur via passive diffusion, hydrogel matrix degradation, or stimuli-responsive triggers, enabling sustained and localized drug delivery. These features, along with their unique combination of natural origin, responsiveness, and versatility, make carbohydrate-based hydrogels particularly suitable for personalized delivering systems [9].

3. Core Concepts in Biosensing and Drug Delivery Carbohydrate-Based Hydrogels

Biosensors are highly sophisticated analytical devices designed to integrate biological recognition elements with transducers, enabling the detection and quantification of specific biological or chemical substances with remarkable sensitivity and selectivity [10]. These devices have gained widespread attention due to their extensive applications in diverse fields such as healthcare, environmental monitoring, food safety, drug development, and industrial processing. A biosensor is typically composed of three fundamental components: a biological recognition element (which may include enzymes, antibodies, nucleic acids, or whole cells), a transducer responsible for converting the biological interaction into a quantifiable signal, and an output system that processes and displays the resulting data. In the case of carbohydrate polymer-based biosensors, these components are typically immobilized or integrated onto the carbohydrate macromolecular structure, which serves as a biocompatible matrix supporting the stability and functionality of the sensing elements (Figure 1).

The immobilization of the biological recognition element onto the transducer allows for the precise detection of target analytes through biochemical interactions, which can be monitored in real time [11]. The principles underlying biosensor technology are based on the specific interaction between the recognition element and the analyte of interest, followed by signal transduction and data analysis [12]. Various types of transducers, such as electrochemical, optical, piezoelectric, and thermal sensors, are used to improve biosensor efficiency. The continuous evolution of nanotechnology, materials science, and microfabrication has significantly increased biosensor performance by enhancing their sensitivity, specificity, and miniaturization. The incorporation of nanostructured materials, including graphene, carbon nanotubes, metallic nanoparticles, and quantum dots, has revolutionized transducer design by expanding surface area, enhancing electronic properties, and improving signal amplification (Figure 2). This advancement has enabled the detection of extremely low analyte concentrations, even at femtomolar or attomolar levels [13]. Furthermore, the advent of multiplex biosensors capable of simultaneously detecting multiple analytes has expanded their applicability in complex biological systems, such as monitoring disease biomarkers in body fluids or identifying contaminants in food and water [14]. In healthcare, biosensors serve as invaluable tools for disease diagnosis, patient monitoring, and therapeutic guidance. Point-of-care (POC) biosensors, such as glucose meters for diabetes management and rapid antigen tests for infectious diseases, exemplify the practical utility of these devices in delivering fast, reliable, and user-friendly solutions [15,16,17]. Beyond the medical field, biosensors significantly contribute to environmental monitoring by enabling the rapid detection of pollutants, pathogens, and toxins in air, water, and soil samples. In the food industry, biosensors play a crucial role in ensuring product safety by detecting harmful contaminants, including pesticides, heavy metals, and microbial pathogens [18]. Additionally, biosensors are widely employed in industrial applications, such as monitoring fermentation processes, optimizing production efficiency, and maintaining product consistency in manufacturing environments [19].

Parallel to biosensor technology, drug delivery systems have evolved significantly, incorporating advanced materials such as carbohydrate hydrogels to enhance therapeutic efficacy. The fundamental principle of drug delivery technology lies in the precise control of drug release to maintain therapeutically active plasma drug concentrations over a defined period. Traditional dosage forms often fail to provide controlled and sustained drug release, leading to fluctuations in drug levels and reduced treatment efficiency [20]. Advances in pharmacokinetics have shifted research towards developing innovative drug carriers that release predetermined doses of therapeutic agents at specific sites and times, aligning with disease pathology and patient needs. Carbohydrate-based hydrogels have emerged as one of the most promising candidates for drug delivery applications due to their tunable physicochemical properties and high biocompatibility [21]. By modifying the affinity for water and the density of crosslinks within their macromolecular structure, the porosity of hydrogels can be precisely controlled, influencing drug entrapment and release profiles. Carbohydrate-based hydrogels are available in various forms, including films, beads, microparticles, and nanoparticles, making them versatile materials for biomedical applications such as cell immobilization, biomolecule separation, diagnostics, tissue engineering, and regenerative medicine. This inherent biocompatibility enables them to act as protective carriers, shielding drugs from enzymatic degradation and enhancing therapeutic stability. The high water content and soft texture of carbohydrate hydrogels closely resemble living tissues. Moreover, carbohydrate-based hydrogels exhibit low interfacial tension, minimizing protein adsorption from bodily fluids and facilitating the diffusion of drugs into and out of swollen hydrogel networks [22]. These properties make carbohydrate hydrogels suitable for a wide range of drug delivery routes, including vaginal, ocular, nasal, oral, rectal, buccal, and parenteral administration. Moreover, carbohydrate macromolecules can be in the form of “smart hydrogels” that represent an advanced class of drug delivery materials that dynamically respond to physiological variations. These hydrogels undergo reversible changes in their chemical and physical properties—such as swelling, mechanical strength, phase transition, optical transparency, surface energy, permeation rate, or reaction rate—upon exposure to specific stimuli. For instance, pH-responsive hydrogels are synthesized by incorporating acidic or basic functional groups onto the polymer backbone, allowing them to undergo ionization in response to environmental pH changes [6]. This process triggers increased electrostatic repulsion, enhances hydrophilicity, and induces higher swelling ratios, resulting in the controlled release of encapsulated drugs. Similarly, thermoresponsive hydrogels undergo sol–gel phase transitions based on temperature variations, making them ideal for injectable drug delivery systems that solidify upon administration. Moreover, carbohydrate hydrogel-based drug delivery systems have been integrated with biosensors to develop theranostic platforms, which combine therapeutic and diagnostic functions [23], enhancing personalized medicine strategies [24,25]. The fabrication of these devices necessitates a precise selection of monomers, crosslinking agents, and polymerization initiators to achieve the intended structural and functional attributes [26,27]. Essential reaction conditions such as temperature, pH, and polymerization duration are meticulously regulated to comply with the required characteristics [28]. These methods guarantee secure anchoring of the hydrogel onto sensor substrates or drug reservoirs while facilitating seamless integration with detection components [29]. For clinical applications, a thorough assessment of critical properties such as mechanical behavior, biocompatibility, stability, sensitivity, and response parameters is imperative. Mechanical properties are especially significant for wearable and implantable devices, as these applications involve exposure to mechanical stress [30]. Biocompatibility and stability are fundamental considerations to ensure safe and prolonged interaction with biological systems. These hydrogels are formulated from materials with minimal cytotoxicity, promoting cell viability and mitigating the risk of adverse reactions in vivo [31]. Furthermore, controlled degradation rates contribute to enhanced stability, allowing these materials to function reliably over extended periods [32]. Sensitivity and specificity are key attributes of carbohydrate hydrogel-based devices, enabling the precise detection of low biomarker concentrations and the controlled release of therapeutic agents [33,34]. The response time and recovery rate of these hydrogels are also crucial, particularly in real-time monitoring applications or controlled drug release mechanisms. Indeed, carbohydrate-based theranostic devices are designed to respond swiftly to physiological changes and revert to baseline conditions upon stimulus removal, ensuring continuous functionality [35]. The mechanisms that convert physiological changes into measurable or releasing signals can be categorized into physical and chemical responsiveness. Physical responsiveness includes the swelling and deswelling behavior of hydrogels in response to environmental factors such as pH, temperature, or ion concentrations, leading to modifications in optical or electrical properties that can be quantified [36,37]. For instance, hydrogels designed for electrolyte monitoring expand in response to sodium ion levels, offering essential data for managing electrolyte imbalances in medical settings [38]. Differently, chemical functionalization enables specific molecular interactions. For example, boronic acid-modified hydrogels undergo structural transformations upon binding to glucose, facilitating non-invasive glucose sensing and regulating insulin delivery [39]. Smart contact lenses embedded with hydrogel sensors can monitor glucose fluctuations in tears via chemically induced fluorescence intensity variations [40]. Chemically functionalized conductive carbohydrate-based hydrogels are used as wearable devices with electrochemical sensitivity [41].

4. Application of Carbohydrate-Based Hydrogel as Theranostic Devices

Carbohydrate-based hydrogels hold significant potential for monitoring physiological indicators and delivering bioactives, offering a broad range of health applications. Their inherent biocompatibility, high sensitivity, and real-time monitoring capabilities make them an emerging and highly promising technology in the medical field [42] (Figure 3).

4.1. Monitoring Cardiac Wellness

Carbohydrate hydrogel sensors have garnered significant attention for their ability to monitor various physiological parameters with high sensitivity, adaptability, and exceptional biocompatibility. For example, their application as heart rate monitoring devices presents considerable improvements over conventional metal electrodes. Traditional metal electrodes, frequently employed for real-time electrocardiogram (ECG) monitoring in clinical settings, often exhibit rigidity and limited flexibility, leading to discomfort and potential skin irritation during prolonged use [43]. Hydrogel electrodes address these challenges by combining the superior electrical conductivity of metallic components with a soft, conformable alginate hydrogel matrix that ensures better skin contact and enhanced biocompatibility [43]. This innovation significantly reduces the risk of skin irritation and allergic reactions, improving patient comfort during continuous physiological monitoring. This system exhibited outstanding reproducibility in capturing ECG signals, maintaining its functional stability even after prolonged usage. Unlike metal electrodes, the hydrogel-based variant did not induce any adverse dermatological reactions, reinforcing its potential for extended wear in long-term health monitoring applications [43]. To further advance wearable ECG technology, Xu et al. [44] designed an alternative hydrogel-based ECG electrode utilizing Poly(3,4-ethylenedioxythiophene)/poly(styrenesulfonate) (PEDOT:PSS) combined with commercially available flexible substrates based on geniposide, an iridoid glycoside. This hydrogel electrode was fabricated as a wearable skin patch capable of accurately detecting ECG signals under both static and dynamic conditions in volunteer test subjects [44]. In a parallel study, Lee et al. [45] engineered self-adherent, biocompatible geniposide-based hydrogel electrodes composed of biodegradable gelatin and PEDOT:PSS as a conductive polymer for ECG signal acquisition. By crosslinking gelatin with geniposide, they achieved significant enhancements in mechanical durability and electrical performance. The device demonstrated comparable accuracy in 12-lead human ECG measurements when tested against standard commercial ECG electrodes such as the 3M Red Dot [45]. The applications discussed are concisely outlined in

Table 1. Carbohydrate-based hydrogel biosensors for the monitoring of cardiac wellness.

Material	Applications	Characteristics	Reference
Self-healing alginate hydrogel electrode with anti-freezing and moisturizing properties	Real-time ECG monitoring	Excellent electrical conductivity, soft and flexible, no adverse skin reactions, high reproducibility, suitable for long-term health monitoring.	[43]
Self-adherent, biocompatible hydrogel electrodes composed of biodegradable gelatin, geniposide and poly(3,4-ethylenedioxythiophene)/poly(4-styrenesulfonate)	Real-time ECG monitoring	Device designed to form a patch and used as a wearable device to detect the ECG signals of volunteer from static to dynamic conditions.	[44]
Self-adherent, biocompatible hydrogel electrodes composed of crosslinked gelatin, geniposide and poly(3,4-ethylenedioxythiophene)/poly(4-styrenesulfonate)	Real-time ECG monitoring	Improved mechanical properties and electrical conductivity. Comparable performance in 12-lead human ECG measurement with commercial ECG clinical electrodes (3M Red Dot).	[45]

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4.2. Respiratory Monitoring

Real-time respiratory monitoring in humans is essential for the early detection and management of disorders associated with sleep deprivation, such as obstructive sleep apnea syndrome (OSAS). However, creating respiratory monitoring devices that seamlessly integrate high sensitivity, comfort, portability, and environmental stability remains a formidable challenge. To address these limitations, researchers have engineered advanced multimodal hydrogel sensors designed explicitly for OSAS diagnosis and continuous respiration tracking, ensuring exceptional performance standards. These state-of-the-art sensors exploit cellulose-based hydrogels with chemically crosslinked networks, where hydrogen bonding interactions play a pivotal role in enhancing material properties [46]. The unique structural composition of these hydrogels imparts superior mechanical strength and extreme resistance to temperature fluctuations, ensuring robustness and reliability in diverse environmental conditions. These carbohydrate hydrogel-based sensors function through a dual-sensing mechanism, independently detecting mechanical and thermal changes by leveraging resistor and capacitor output signals, respectively. This multimodal sensing strategy not only enables the precise detection of respiratory anomalies but also provides a dependable framework for OSAS diagnosis. The combined effect of mechanical and thermal outputs enhances the consistency and accuracy of respiratory event detection, making these sensors indispensable in preventing sleep-related health complications, improving patient care, and advancing respiratory health surveillance technologies [46]. Continuous respiratory and motion monitoring holds immense significance in health surveillance and disease prevention. Despite the existing challenges, the need for high-precision, multifunctional, portable, and adaptive sensors for healthcare applications is more pressing than ever. In response to this demand, Liu et al. introduced a novel respiratory monitoring and posture recognition system incorporating a hydrogel electrolyte that is compatible with supercapacitors and multimodal wearable sensors [47]. The hydrogel electrolyte, composed of polyvinyl alcohol, aluminum hydroxide, and starch, exhibits exceptional flexibility and adaptability, enabling it to function efficiently across diverse conditions. This innovative system independently measures mechanical and thermal variations through corresponding resistor and capacitor signals, enhancing its versatility and reliability for comprehensive physiological monitoring [47]. Furthermore, to optimize detection accuracy, an artificial neural network was integrated into the monitoring framework, achieving a remarkable 99.259% recognition accuracy. The application of machine learning in this system significantly improves its diagnostic capabilities, particularly in recognizing and classifying OSAS events. The combination of hydrogel-based sensing materials and artificial intelligence underscores the potential of these devices as highly accurate and efficient diagnostic tools for respiratory disorders [47]. The cited findings are summarized in

Table 2. Carbohydrate-based hydrogel biosensors for respiratory monitoring.

Material	Applications	Characteristics	Reference
Cellulose-based hydrogel	Real-time respiratory monitoring, OSAS diagnosis	Outstanding tensile strength, extreme resistance to temperature fluctuations, multimodal sensing (mechanical and thermal changes), high robustness and reliability.	[46]
Hydrogel electrolyte (polyvinyl alcohol, aluminum hydroxide, and starch)	Respiration monitoring, posture recognition	Superior flexibility and adaptability, multimodal functionality (mechanical and thermal signals), integrated with machine learning (99.259% recognition accuracy).	[47]

.

4.3. Drug Delivery Devices

Carbohydrate-based hydrogels are versatile carriers for drug delivery via oral, buccal, rectal, nasal, and vaginal routes. They are effective in treating localized conditions in the mouth, such as oral cancer and osteoporosis (Figure 4).

Hydrogels are extensively researched for pharmaceutical and biomedical applications, including transdermal drug delivery. Polysaccharide-based hydrogels are favored due to their biocompatibility, non-toxic nature, degradability, and ability to release drugs in a controlled manner. Their cost-effectiveness, ease of production, and adaptability for large-scale manufacturing further enhance their appeal. For instance, collagen-based hydrogel masks containing sodium hyaluronate help maintain skin elasticity, hydration, and a healthy glow by providing essential nutrients [48]. Hydrogels designed for colon-specific delivery are being developed to treat diseases such as Crohn’s disease, colon cancer, and ulcerative colitis. These hydrogels leverage the high concentration of polysaccharide enzymes in the colon to enable site-specific drug release. By altering enzymatic activity or utilizing pH-sensitive mechanisms, hydrogels can deliver drugs like ibuprofen at a controlled rate, as seen with psyllium-based hydrogels [49] or crosslinked guar gum hydrogels [50]. Hydrogels have been extensively utilized in ophthalmology for drug delivery, controlled release systems, and regenerative medicine. Their 3D network enables responsiveness to stimuli like pH and temperature, making them suitable for drug-eluting soft contact lenses and intraocular lenses. Examples include gel-forming polymers like xyloglucan for the sustained delivery of pilocarpine [51] and timolol [52]. Products such as Hylo^® Gel (made of hyaluronic acid) provide prolonged lubrication for treating dry eyes, while Lacrisert^® (made of hydroxypropyl cellulose) is designed for conditions like cytomegalovirus-associated retinitis in acquired immunodeficiency syndrome (AIDS) patients [53,54,55,56]. Cancer remains one of the most challenging diseases globally, often treated with chemotherapeutics that cause severe side effects. Thermoresponsive hydrogels, such as those based on chitosan–poly(N-isopropyl acrylamide-co-acrylamide), have been developed for drug delivery in tumor environments. These hydrogels exploit the increased temperature of cancerous tissues to release drugs in a temperature-dependent manner, enhancing treatment efficacy [57]. Hydrogels have been investigated for gynecological uses such as contraception and vaginal tissue engineering. Non-hormonal contraceptive hydrogels combining styrene-maleic anhydride (SMA) with biodegradable carbohydrate-based materials like cyclodextrins offer an alternative to hormonal contraceptives while minimizing side effects. Thermosensitive hydrogels, which transition from liquid to gel at body temperature, have been utilized for vaginal health, infection treatment, and contraceptive purposes. These hydrogels also enhance drug retention and controlled release within the vaginal environment [58,59,60,61]. Hydrogels are also used in breast implants, providing alternatives to silicone-based materials. For example, implants filled with hydroxyl propyl cellulose gel offer a biodegradable and radiolucent option with reduced capsular contraction and a more natural feel, making them particularly suitable for breast cancer patients [62]. The buccal route is highly advantageous for drug delivery due to its rapid action, minimal side effects, and high permeability. Mucoadhesive hydrogels made from materials like chitosan, hydroxyethylcellulose, and polyacrylic resins enhance drug delivery to the oral cavity. Hydrogels are highly effective for wound management due to their ability to maintain a moist environment, provide a barrier against microbes, and ensure biocompatibility. Materials like agar are commonly used for dressing wounds, offering flexibility, softness, and non-thrombogenic properties [63,64]. García-Astrain and Avérous [65] engineered pH-sensitive hydrogels using modified alginate, aiming to improve drug release profiles. Their study showed a pronounced dependence of the swelling behavior on the surrounding pH, ranging from acidic to basic environments (pH 1–13). Similarly, Zhang et al. [66] formulated injectable hydrogels using hyperbranched mushroom polysaccharides in combination with xanthan gum, demonstrating effective ciprofloxacin delivery as measured by UV–Vis spectroscopy at 277 nm. Huang et al. [67] synthesized injectable hydrogels by crosslinking aldehyde-functionalized xanthan gum (Xan-CHO) with carboxymethyl chitosan, achieving excellent rheological recovery and enhanced resistance to enzymatic degradation over 72 h. Huh et al. [68] created an organic–inorganic hydrogel matrix based on hyaluronic acid and poloxamer, highlighting its potential for biomineralization via urea-induced mineral deposition, particularly useful in bone regeneration. Jung et al. [69] combined hyaluronic acid with Pluronic F-127 to develop hydrogels for the delivery of nonsteroidal anti-inflammatory drugs (NSAIDs), showing that the latter significantly delayed drug release beyond 50 h. Liu et al. [70] incorporated β-cyclodextrin, epichlorohydrin, and succinic anhydride into hydrogels tailored for anti-inflammatory purposes. Using indomethacin as a model drug, they demonstrated the effective prevention of inflammation during bone biomineralization processes. Yang et al. [71] reported the design of carbohydrate-based hydrogels using methoxy polyethylene glycol (mPEG), alginate, and carboxymethyl chitosan for oral drug delivery in dental applications. Their findings emphasized that the alginate ratio played a key role in enhancing delivery performance. In another study, Emman and Shaheen [72] utilized esterified cellulose to produce smart hydrogels responsive to both pH and temperature. The modification not only improved hydrophobicity but also enabled dual responsiveness, making the system suitable for complex physiological environments. Yang et al. [73] further explored oral delivery systems by embedding β-cyclodextrin-loaded microparticles into carboxymethyl chitosan hydrogels, achieving sustained insulin release over 12 h. This layered approach to hydrogel design significantly enhanced drug retention and bioavailability. Anugrah et al. [74] investigated the effect of near-infrared (NIR) light on alginate-based hydrogels containing doxorubicin. NIR exposure promoted additional crosslinking within the hydrogel matrix, enabling precise control over drug release kinetics. Xu et al. [75] synthesized thermoresponsive hydrogels using alkylated chitosan and poly(N-isopropylacrylamide). The release of diclofenac sodium was notably prolonged, with 25% of the drug released over 300 min. Maiz-Fernández et al. [76] fabricated hydrogels from β-glycerol phosphate and genipin-crosslinked chitosan, optimizing them for diclofenac delivery. Their mechanical and rheological testing confirmed the suitability of these materials for biomedical use. Lastly, Yuan et al. [77] reported a hybrid hydrogel system consisting of chitosan and polycaprolactone, designed for rifampicin delivery. The formulation exhibited potent antibacterial activity against Klebsiella pneumoniae and Staphylococcus aureus, further validating the multifunctionality of these carbohydrate-based systems. The described applications are summarized in

Table 3. Carbohydrate-based hydrogels as drug delivery systems.

Material	Applications	Characteristics	Reference
Collagen-based hydrogel masks containing sodium hyaluronate	Maintain skin elasticity, hydration, and a healthy glow	Ability to provide essential nutrients to skin	[48]
pH-responsive psyllium and methacrylamide-based hydrogels	Colon specific drug delivery	These hydrogels leverage the high concentration of polysaccharide enzymes in the colon and pH responsivity to enable site-specific drug release	[49]
Crosslinked guar gum hydrogel disks	Colon-specific delivery of ibuprofen	Altering enzymatic activity or utilizing pH-sensitive mechanisms, this hydrogel can deliver ibuprofen at a controlled rate	[50]
Gel-forming xyloglucan	Sustained delivery of pilocarpine	The 3D network enables responsiveness to stimuli like pH and temperature, making this hydrogel suitable for drug-eluting soft contact lenses and intraocular lenses	[51]
Gel-forming xyloglucan	Sustained delivery of timolol	The 3D network enables responsiveness to stimuli like pH and temperature, making this hydrogel suitable for drug-eluting soft contact lenses and intraocular lenses	[52]
Thermoresponsive hydrogel based on chitosan–poly(N-isopropyl acrylamide-co-acrylamide)	Drug delivery in tumor environments	These hydrogels exploit the increased temperature of cancerous tissues to release drugs in a temperature-dependent manner, enhancing treatment efficacy	[57]
Cyclodextrin hydrogels and deformable propylene glycol liposomes-in-hydrogel	Vaginal delivery of dehydroepiandrosterone, carboplatin, and clotrimazole	Enhance drug retention and controlled release within the vaginal environment	[58,59,60,61]
Breast implants filled with hydroxyl propyl cellulose gel	Delivery of antioxidant bioactives	Biodegradable and radiolucent gel with reduced capsular contraction particularly suitable for breast cancer patients	[62]
Polyvinyl pyrrolidine, agar, and PEG-based hydrogels	Dressing for wound management	Ability to maintain a moist environment and to provide a barrier against microbes, offering flexibility, softness, and non-thrombogenic properties	[63,64]
pH-sensitive hydrogels using modified alginate	Drug delivery device	Pronounced dependence of the swelling behavior on the surrounding pH, ranging from acidic to basic environments	[65]
Injectable hydrogels using hyperbranched mushroom polysaccharides in combination with xanthan gum	System for ciprofloxacin delivery	Optimal release properties	[66]
Injectable hydrogels by crosslinking aldehyde-functionalized xanthan gum with carboxymethyl chitosan	Drug delivery device	Excellent rheological recovery and enhanced resistance to enzymatic degradation over 72 h	[67]
Organic–inorganic hydrogel matrix based on hyaluronic acid and poloxamer	Bone regeneration delivery device	Potential for biomineralization via urea-induced mineral deposition, particularly useful in bone regeneration	[68]
Hyaluronic acid with Pluronic F-127 hydrogels	Hydrogels for NSAID delivery	Drug release beyond 50 h	[69]
β-cyclodextrin, epichlorohydrin, and succinic anhydride hydrogels delivering indomethacin	Anti-inflammatory DDS	Effective prevention of inflammation during bone biomineralization processes	[70]
Hydrogels of methoxy polyethylene glycol, alginate, and carboxymethyl chitosan	Oral drug delivery in dental applications	Alginate ratio played a key role in enhancing delivery performance	[71]
Smart hydrogels of esterified cellulose	Responsive drug delivery system	Improved hydrophobicity and dual responsiveness to pH and temperature, making the system suitable for complex physiological environments	[72]
β-cyclodextrin-loaded microparticles into carboxymethyl chitosan hydrogel	Oral delivery system for insulin	Sustained insulin release over 12 h. Enhanced drug retention and bioavailability	[73]
Alginate-based hydrogels containing doxorubicin	Drug delivery system	NIR exposure promoted additional crosslinking within the hydrogel matrix, enabling precise control over drug release kinetics.	[74]
Thermoresponsive hydrogels using alkylated chitosan and poly(N-isopropylacrylamide) for diclofenac release	Anti-inflammatory drug delivery device	Prolonged diclofenac release, with 25% of the drug released over 300 min	[75]
Hydrogels from β-glycerol phosphate and genipin-crosslinked chitosan	System for diclofenac delivery	Mechanical and rheological properties suitable for biomedical use	[76]
Hybrid hydrogel system consisting of chitosan and polycaprolactone	System for rifampicin delivery	This formulation exhibited potent antibacterial activity against Klebsiella pneumoniae and Staphylococcus aureus	[77]

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5. Conclusions and Future Remarks

The utilization of hydrogel-enabled solutions underscores a profound transformation in the healthcare landscape. Traditional diagnostic tools, often limited by their rigidity, invasiveness, or reliance on external laboratory analyses, frequently place a significant burden on patients in terms of time, discomfort, and accessibility [78]. In contrast, hydrogel-based theranostic systems represent a revolutionary leap forward by offering non-invasive, real-time monitoring solutions that are more in tune with the body’s natural physiology. These devices, crafted from soft and biocompatible materials, seamlessly integrate with biological systems, enabling the continuous monitoring of vital biomarkers such as glucose, lactate, and pH levels directly on or within the body. In addition, bioactives can be directly released into the site of action through these macromolecular systems. These functionalities not only reduce the need for frequent hospital visits but also empower patients with actionable insights about their health in real time. Carbohydrate-based theranostic devices can be engineered to respond to specific stimuli, such as temperature changes, mechanical stress, or chemical imbalances, enabling precise and dynamic feedback tailored to individual patient needs. For example, a hydrogel sensor embedded in a wound dressing can monitor infection indicators like pH or bacterial load, simultaneously delivering therapeutic agents when required. This dual diagnostic–therapeutic capability exemplifies the concept of “smart” healthcare, where devices not only identify problems but also initiate solutions autonomously, reducing response times and improving outcomes [79]. Another critical advantage of hydrogel systems lies in their ability to enhance patient comfort and adherence. Unlike rigid devices or invasive sampling techniques, these devices conform to the body’s contours, minimizing discomfort and the risk of irritation. This property is particularly beneficial in long-term monitoring and curative scenarios, such as managing chronic conditions like diabetes or cardiovascular diseases, where traditional approaches can lead to patient fatigue or non-compliance. By making health monitoring and drug administration compliance more intuitive and less intrusive, hydrogel-based systems encourage patients to actively participate in their care, fostering a sense of empowerment and responsibility [80]. From a technological perspective, the development of hydrogel-based biosensors and drug delivery devices marks a significant milestone in material science and engineering [81]. Their porous structure allows for the efficient exchange of molecules, ensuring the rapid and accurate detection or release of biomarkers. Moreover, hydrogels can be functionalized with specific enzymes, antibodies, or nanoparticles, further enhancing their sensitivity and selectivity. These advancements have introduced applications beyond conventional settings, such as wearable sensors for athletes, implantable devices for continuous disease management, and point-of-care diagnostics in remote or resource-limited areas. The impact of these devices extends beyond individual patient benefits, influencing the broader healthcare ecosystem. Carbohydrate hydrogel-enabled solutions align with the growing trend of decentralizing healthcare, shifting diagnostic and curative capabilities from centralized laboratories to the patient’s immediate environment [82]. This decentralization not only reduces the strain on healthcare infrastructure but also enables the earlier detection of diseases, potentially preventing complications and reducing treatment costs. Ethical and accessibility considerations also underscore the importance of hydrogel-based diagnostics and therapy in advancing equitable healthcare. By simplifying diagnostic processes and reducing dependence on expensive laboratory equipment, these devices can make high-quality care more accessible to underserved populations [83]. For instance, low-cost hydrogel patches capable of monitoring hydration levels or detecting infectious diseases could revolutionize healthcare delivery in rural or low-income settings [84]. Additionally, their environmental friendliness, due to biodegradable and sustainable material options, addresses concerns about the ecological impact of disposable medical devices [85]. Beyond diagnostics, hydrogels play a crucial role in drug delivery systems, further expanding their potential in modern medicine. For example, pH-sensitive hydrogels can release anti-inflammatory drugs at sites of infection, while thermoresponsive hydrogels can facilitate on-demand drug administration for conditions like cancer or post-surgical pain management. Additionally, hydrogel-based drug carriers enhance the bioavailability of poorly soluble drugs and provide protective environments for sensitive biomolecules such as proteins and nucleic acids. These properties make hydrogels a promising platform for advanced therapeutic applications, including gene therapy, regenerative medicine, and precision oncology, reinforcing their role in the evolution of smart healthcare systems. However, technical constraints, including limitations in the speed of data processing and the mechanical properties of the materials, pose barriers to fully realizing the potential of these sensors [86]. Looking to the future, the evolution of hydrogel-based devices will likely be driven by advancements in materials science and in micro-nanofabrication techniques. By developing more durable and responsive materials, future hydrogel sensors will be capable of detecting a wider range of physiological signals with greater precision. This will facilitate a new era of personalized medicine, where health interventions can be precisely adapted to the unique needs of each patient. Moreover, the ongoing trend toward miniaturization and integration with wearable technologies will make hydrogel sensors and drug delivery systems more accessible and user-friendly [87].