Advancements in hydrogels: A comprehensive review of natural, synthetic, and hybrid innovations for wound healing.

Cardiac fibroblasts' (FBs) and cardiomyocytes' (CMs) behaviour and morphology are influenced by their environment such as remodelling of the myocardium, thus highlighting the importance of biomaterial substrates in cell culture. Biomaterials have emerged as important tools for the development of physiological models, due to the range of adaptable properties of these materials, such as degradability and biocompatibility. Biomaterial hydrogels can act as alternative substrates for cellular studies, which have been particularly key to the progression of the cardiovascular field. This review will focus on the role of hydrogels in cardiac research, specifically the use of natural and synthetic biomaterials such as hyaluronic acid, polydimethylsiloxane and polyethylene glycol for culturing induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). The ability to fine-tune mechanical properties such as stiffness and the versatility of biomaterials is assessed, alongside applications of hydrogels with iPSC-CMs. Natural hydrogels often display higher biocompatibility with iPSC-CMs but often degrade quicker, whereas synthetic hydrogels can be modified to facilitate cell attachment and decrease degradation rates. iPSC-CM structure and electrophysiology can be assessed on natural and synthetic hydrogels, often resolving issues such as immaturity of iPSC-CMs. Biomaterial hydrogels can thus provide a more physiological model of the cardiac extracellular matrix compared to traditional 2D models, with the cardiac field expansively utilising hydrogels to recapitulate disease conditions such as stiffness, encourage alignment of iPSC-CMs and facilitate further model development such as engineered heart tissues (EHTs).

Natural polymer-based hydrogels, generally composed of hydrophilic polymers capable of absorbing large amounts of water, have garnered attention for biomedical applications because of their biocompatibility, biodegradability, and eco-friendliness. Natural polymer-based hydrogels derived from alginate, starch, cellulose, and chitosan are particularly valuable in fields such as drug delivery, wound dressing, and tissue engineering. However, compared with synthetic hydrogels, their poor mechanical properties limit their use in load-bearing applications. This review explores recent advancements in the enhancement of the mechanical strength of natural hydrogels while maintaining their biocompatibility for biomedical applications. Strategies such as chemical modification, blending with stronger materials, and optimized cross-linking are discussed. By improving their mechanical resilience, natural hydrogels can become more suitable for demanding biomedical applications, like tissue scaffolding and cartilage repair. Additionally, this review identifies the ongoing challenges and future directions for maximizing the potential of natural polymer-based hydrogels in advanced medical therapies.

Research progress of natural polysaccharide-based and natural protein-based hydrogels for bacteria-infected wound healing

3D bioprinting has recently gained popularity due to its inherent capability of releasing cell-seeded and cell-laden biomaterials in a defined location to fabricate patient-specific scaffolds. Multi-nozzle extrusion-based 3D bio-printing allows the fabrication of various natural and synthetic biopolymers and the investigations of material to material and cell to material interactions, and eventually with a high percentage of cell viability and proliferation. Although natural hydrogels are demanding candidates for bio-printing because of their biocompatibility and high-water content, ensuring the scaffold’s fidelity with only natural hydrogel polymers is still challenging. Polycaprolactone (PCL) is a potential synthetic bioprinting material that can provide improved mechanical properties for fabricated scaffolds, especially bone and cartilage scaffolds. In this paper, application-oriented structural viability such as 3D printability, shape fidelity, and mechanical properties of the scaffolds fabricated by PCL and other natural hydrogel materials will be investigated. Scaffolds will be fabricated using various natural hybrid hydrogels such as Alginate-Carboxymethyl Cellulose; Alginate-Carboxymethyl Cellulose-TEMPO NFC, and PCL simultaneously using various infill densities, applied pressures, print speeds, and toolpath patterns. Shape fidelities of printed scaffolds will be analyzed. This research can help identify optimum natural-synthetic polymer combinations based on the materials interaction, external and internal geometries, and mechanical properties for large-scale multi-material bio fabrication.

Worldwide, the prevalence of osteoarthritis has grown significantly in recent years, and the rate of growth is accelerating. In recent years, the number of people with osteoarthritis has increased rapidly worldwide, and the rate of increase is on the rise. The development of osteoarthritis at an advanced stage can cause significant physical and psychological damage to patients. This article will introduce the application of natural and synthetic hydrogels in the field of osteoarthritis treatment. Natural hydrogels such as gelatin, alginate and polysaccharide have good biocompatibility and biodegradability and can be used for intra-articular drug delivery after modification. Synthetic hydrogels such as polyvinyl alcohol, polyethylene glycol and poly (lactic acid-hydroxyacetic acid) copolymer have good mechanical properties and can be used for intra-articular drug delivery and joint lubricants. In this article describes the application of hydrogels to carry a range of drugs and cell growth factors for the treatment of osteoarthritis, to act as scaffolds for cell growth, to lubricate joint cavities, and to reduce loads on joints, as well as several hydrogel modification methods to give them better biological or mechanical properties.

Methods for culturing mammalian cells ex vivo are increasingly needed to study cell and tissue physiology and to grow replacement tissue for regenerative medicine. Two-dimensional culture has been the paradigm for typical in vitro cell culture; however, it has been demonstrated that cells behave more natively when cultured in three-dimensional environments. Permissive, synthetic hydrogels and promoting, natural hydrogels have become popular as three-dimensional cell culture platforms; yet, both of these systems possess limitations. In this perspective, we discuss the use of both synthetic and natural hydrogels as scaffolds for three-dimensional cell culture as well as synthetic hydrogels that incorporate sophisticated biochemical and mechanical cues as mimics of the native extracellular matrix. Ultimately, advances in synthetic-biologic hydrogel hybrids are needed to provide robust platforms for investigating cell physiology and fabricating tissue outside of the organism.

Hydrogel materials are pivotal in bioprinting due to their biomimetic properties, high water content, and biocompatibility, which facilitate cell viability and tissue regeneration. This paper comprehensively analyzes hydrogel-based bioprinting, focusing on material classification, printing technologies, and clinical applications. Key findings reveal that natural hydrogels (e.g., gelatin, alginate, hyaluronic acid) offer superior bioactivity, while synthetic hydrogels (e.g., PEGDA) provide tunable mechanical strength and high-resolution printability. Composite hydrogels (e.g., GelMA/alginate) synergistically combine these advantages, enhancing structural fidelity and cellular support. Advanced extrusion and vat photopolymerization techniques (e.g., SLA/DLP) have achieved resolutions down to 25 m and cell viability exceeding 95%, enabled by innovations like visible-light curing and granular microgel assembly. Computational modeling and machine learning further optimize bioink formulation and printing parameters. Despite progress, clinical translation faces barriers including standardization gaps, scalability challenges, and cost constraints. Future research must prioritize dynamic, multi-stimuli-responsive "smart hydrogels" and metabolic function emulation for complex organs. This work underscores hydrogels transformative potential in regenerative medicine while outlining pathways to overcome translational hurdles.

Acute skin damage caused by burns or cuts occurs frequently in people’s daily lives. Such wounds are difficult to heal normally and have persistent inflammation. Wound dressings not only improve the speed of wound healing, but also protect and cover the wound well. Hydrogels have the characteristics of good flexibility, high water content, and good biocompatibility, and are widely used in biomedicine and other fields. Common hydrogels are mainly natural hydrogels and synthetic hydrogels. Hydrogels cross-linked using different raw materials and different methods have different performance characteristics. Natural hydrogels prepared using polysaccharides are simple to obtain and have good biocompatibility, but are inferior to synthetic hydrogels in terms of mechanical properties and stability, and a single polysaccharide hydrogel cannot meet the component requirements for wound healing. Therefore, functional composite hydrogels with high mechanical properties, high biocompatibility, and high antibacterial properties are the current research hotspots. In this review, several common polysaccharides for hydrogel synthesis and the synthesis methods of polysaccharide hydrogels are introduced, and functional composite hydrogel dressings from recent years are classified. It is hoped that this can provide useful references for relevant research in this field.

Natural hydrogel dressings in wound care: Design, advances, and perspectives

Dentin–pulp complex is a term which refers to the dental pulp (DP) surrounded by dentin along its peripheries. Dentin and dental pulp are highly specialized tissues, which can be affected by various insults, primarily by dental caries. Regeneration of the dentin–pulp complex is of paramount importance to regain tooth vitality. The regenerative endodontic procedure (REP) is a relatively current approach, which aims to regenerate the dentin–pulp complex through stimulating the differentiation of resident or transplanted stem/progenitor cells. Hydrogel-based scaffolds are a unique category of three dimensional polymeric networks with high water content. They are hydrophilic, biocompatible, with tunable degradation patterns and mechanical properties, in addition to the ability to be loaded with various bioactive molecules. Furthermore, hydrogels have a considerable degree of flexibility and elasticity, mimicking the cell extracellular matrix (ECM), particularly that of the DP. The current review presents how for dentin–pulp complex regeneration, the application of injectable hydrogels combined with stem/progenitor cells could represent a promising approach. According to the source of the polymeric chain forming the hydrogel, they can be classified into natural, synthetic or hybrid hydrogels, combining natural and synthetic ones. Natural polymers are bioactive, highly biocompatible, and biodegradable by naturally occurring enzymes or via hydrolysis. On the other hand, synthetic polymers offer tunable mechanical properties, thermostability and durability as compared to natural hydrogels. Hybrid hydrogels combine the benefits of synthetic and natural polymers. Hydrogels can be biofunctionalized with cell-binding sequences as arginine–glycine–aspartic acid (RGD), can be used for local delivery of bioactive molecules and cellularized with stem cells for dentin–pulp regeneration. Formulating a hydrogel scaffold material fulfilling the required criteria in regenerative endodontics is still an area of active research, which shows promising potential for replacing conventional endodontic treatments in the near future.

In recent years, dyes have been classified as recalcitrant contaminants in wastewater, exhibiting significant toxicological characteristics for flora, fauna, and humans. Various techniques are currently being studied for the remediation of water contaminated with dyes. Among the most relevant alternative technologies are bioadsorption, biocoagulation, the use of composite materials, advanced oxidation processes, etc. However, these methods have some disadvantages. Similarly, the use of hydrogels specifically designed for the treatment of contaminated water is a viable and effective alternative. This is due to their ability to adsorb large amounts of water, high porosity, and multiple active sites. This research describes dyes, their classification,toxicity, and ecotoxicity. Additionally, it presents some alternative treatments for water remediation, emphasizing the design of hydrogels based on synthetic and natural macromolecules. These hydrogels are proposed as promising materials for the removal of dyes from contaminated water. The aim of this research is to highlight synthetic and natural hydrogels as promising materials for the decontamination of water from dyes.

Agriculture plays a critical role in sustaining life and driving the economy of India. The idea of sustainable agriculture is a holistic approach to meet the demands of food supply while protecting our environment. Through various sources, it has been found out that the country is running out of the main reservoirs of water to irrigate the fields. The present study investigated the possibility to prepare different natural hydrogels using Chia seeds, Flax seed, Gond katira, Arrowroot powder, Tapioca, Agar-agar, Corn starch, Gelatin, Aloe vera, and their comparison with a synthetic hydrogel used in sanitary napkins. On successful formation of natural hydrogels and getting valuable results in their water holding capacity, the work continued to test their potential on growth and development of seeds of two plants: Moong beans (Vigna radiata) and Fenugreek (Trigonella sp.) along with bio-organic fertilizers prepared from onion, garlic and banana respectively. Seeds were sown in soil less media (Coco-coir) and the study of various parameters like phytotoxicity test, seed germination, water consumption, number of leaves, root and shoot length indicated promising results in the establishment and healthy growth of the seedlings. Use of natural biodegradable hydrogels therefore may prove as an easy, low cost and eco-friendly way to establish the seedling development and subsequent productivity at the commercial level under conditions of water scarcity for sustainable agriculture.

Natural hydrogels such as collagen offer desirable properties for tissue engineering, including cell adhesion sites, but their low mechanical strength is not suitable for bladder tissue regeneration. In contrast, synthetic hydrogels such as poly (ethylene glycol) allow tuning of mechanical properties, but do not elicit protein adsorption or cell adhesion. For this reason, we explored the use of composite hydrogel blends composed of Tetronic (BASF) 1107-acrylate (T1107A) in combination with extracellular matrix moieties collagen and hyaluronic acid seeded with bladder smooth muscle cells (BSMC). This composite hydrogel supported BSMC growth and distribution throughout the construct. When compared to the control (acellular) hydrogels, mechanical properties (peak stress, peak strain, and elastic modulus) of the cellular hydrogels were significantly greater. When compared to the 7-day time point after BSMC seeding, results of mechanical testing at the 14-day time point indicated a significant increase in both ultimate tensile stress (4.1–11.6 kPa) and elastic modulus (11.8–42.7 kPa) in cellular hydrogels. The time-dependent improvement in stiffness and strength of the cellular constructs can be attributed to the continuous collagen deposition and reconstruction by BSMC seeded in the matrix. The composite hydrogel provided a biocompatible scaffold for BSMC to thrive and strengthen the matrix; further, this trend could lead to strengthening the construct to match the mechanical properties of the bladder.

Hydrogels have the capability to absorb large amounts of water or biological fluids into their three-dimensional hydrophilic polymer networks. These attractive materials are used to develop food additives, superabsorbents, wound dressing compounds, pharmaceuticals, and biomedical implants and also applied in tissue engineering, regenerative medicines, and controlled-release process. Hydrogels can be obtained from synthetic and/or natural resources. Synthetic hydrogels exhibit high water absorption capacities and proper mechanical strengthMechanical strength, although their applications are being limited because of low biocompatibility and biodegradability as well as the toxicity arisen from unreacted monomers remained in the gel structure. Natural hydrogels are often derived from polysaccharides and proteins. Protein-based hydrogels have substantial advantages such as biocompatibility, biodegradability, tunable mechanical properties, molecular binding abilities, and intelligent responses to external stimuli such as pH, ionic strength, and temperature. Therefore, this kind of hydrogels is known as smart biomaterials for controlled release, tissue engineering, regenerative medicine, and other applications. Protein can be converted to hydrogel using physical, chemical, or enzymatic treatments. To improve their mechanical properties, hybrid hydrogels are synthesized by combining natural polymers with synthetic ones. The main approach to obtain hybrid hydrogels is grafting natural polymers with synthetic one and vice versa. This chapter intends to look over protein-based hydrogels. After brief introduction of protein and its structure, the properties of proteins and peptides used to develop hydrogels, as well as their preparation methods are discussed. The potential applications of these polypeptide-based hydrogels in the fields of superabsorbent development, tissue engineering, and controlled release are reported. Characterization methods for protein-based hydrogels are covered in the final section to determine rheological properties, morphology, and thermal stability.

Natural hydrogels, due to their unique biological properties, have been used extensively for various medical and clinical examinations that are performed to investigate the signs of disease. Recently, complex-crosslinking strategies improved the mechanical properties and advanced approaches have resulted in the introduction of naturally derived hydrogels that exhibit high biocompatibility, with shape memory and self-healing characteristics. Moreover, the creation of self-assembled natural hydrogels under physiological conditions has provided the opportunity to engineer fine-tuning properties. To highlight recent studies of natural-based hydrogels and their applications for medical investigation, a critical review was undertaken using published papers from the Science Direct database. This review presents different natural-based hydrogels (natural, natural-synthetic hybrid and complex-crosslinked hydrogels), their historical evolution, and recent studies of medical examination applications. The application of natural-based hydrogels in the design and fabrication of biosensors, catheters and medical electrodes, detection of cancer, targeted delivery of imaging compounds (bioimaging) and fabrication of fluorescent bioprobes is summarised here. Without doubt, in future, more useful and practical concepts will be derived to identify natural-based hydrogels for a wide range of clinical examination applications.