Yuyao Wang, Dou Jin, Zichen Huang, Fan Chen, Kun Liu, Xiacong Zhang
Dynamic covalent hydrogels exhibiting multi-responsive and antibacterial properties offer significant potential for biomedical applications, including smart wound dressings and controlled drug delivery. Herein, a series of amphiphilic quaternized copolymers (Q-C8PEG-n) with tunable quaternization degrees was synthesized from C8PEG via iodomethane addition and characterized by 1H NMR, COSY, FTIR, UV-vis spectroscopy, DLS, TEM, and zeta potential analyses, confirming successful quaternization and micelle formation. These copolymers displayed thermosensitive behavior, with cloud point temperatures increasing due to enhanced hydrophilicity. Q-C8PEG-3 micelles, incorporating diethanolamine units, were crosslinked with phenylboronic acid-grafted hyaluronic acid (HA-PBA) to yield dynamic covalent hydrogels (Gel) through reversible boronic ester bonds stabilized by B-N coordination. The Gel exhibited multi-responsiveness, undergoing degradation in acidic or alkaline conditions and exposure to glucose or H2O2. SEM confirmed a porous microstructure, enabling efficient drug encapsulation, as demonstrated by the release of Nile red (NR). In vitro antibacterial tests revealed enhanced post-quaternization efficacy, with the Gel showing strong activity against S. aureus. This micelle-crosslinked platform synergistically combines tunable stimuli-responsiveness with inherent antibacterial properties, holding promise for applications in wound healing and tissue engineering.
{"title":"Multi-Responsive and Antibacterial Dynamic Covalent Hydrogels Cross-Linked by Amphiphilic Copolymer Micelles.","authors":"Yuyao Wang, Dou Jin, Zichen Huang, Fan Chen, Kun Liu, Xiacong Zhang","doi":"10.3390/gels12010027","DOIUrl":"10.3390/gels12010027","url":null,"abstract":"<p><p>Dynamic covalent hydrogels exhibiting multi-responsive and antibacterial properties offer significant potential for biomedical applications, including smart wound dressings and controlled drug delivery. Herein, a series of amphiphilic quaternized copolymers (Q-C8PEG-n) with tunable quaternization degrees was synthesized from C8PEG via iodomethane addition and characterized by <sup>1</sup>H NMR, COSY, FTIR, UV-vis spectroscopy, DLS, TEM, and zeta potential analyses, confirming successful quaternization and micelle formation. These copolymers displayed thermosensitive behavior, with cloud point temperatures increasing due to enhanced hydrophilicity. Q-C8PEG-3 micelles, incorporating diethanolamine units, were crosslinked with phenylboronic acid-grafted hyaluronic acid (HA-PBA) to yield dynamic covalent hydrogels (Gel) through reversible boronic ester bonds stabilized by B-N coordination. The Gel exhibited multi-responsiveness, undergoing degradation in acidic or alkaline conditions and exposure to glucose or H<sub>2</sub>O<sub>2</sub>. SEM confirmed a porous microstructure, enabling efficient drug encapsulation, as demonstrated by the release of Nile red (NR). In vitro antibacterial tests revealed enhanced post-quaternization efficacy, with the Gel showing strong activity against <i>S. aureus</i>. This micelle-crosslinked platform synergistically combines tunable stimuli-responsiveness with inherent antibacterial properties, holding promise for applications in wound healing and tissue engineering.</p>","PeriodicalId":12506,"journal":{"name":"Gels","volume":"12 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12841037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146051532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Confectionery products, specifically jelly and gummy, require optimized structural, thermal, and nutritional properties for functionality and consumer acceptance. This study investigated the impact of furcellaran (FUR) and calcium L-threonate (Ca) on the physicochemical and the sensory properties of fish gelatin-based jelly (JFG). Furcellaran modestly enhanced gel strength and hardness, while its combination with calcium L-threonate produced synergistic improvements, with JFG-FUR-Ca achieving the highest gel strength (947.63 g) and hardness (78.14 N). Microstructural and intermolecular force analyses indicated that Ca2+ bridging between gelatin and furcellaran promoted ionic and hydrogen bonding, forming a dense and thermostable network. The combined incorporation of furcellaran and calcium L-threonate enhanced the rheological properties while preserving low syneresis. Sensory evaluation revealed minor reductions; however, overall acceptability was higher than 7. Calcium bioavailability after digestion through the gastrointestinal tract model remained high (70-80%), confirming effective calcium fortification. The synergistic incorporation of furcellaran and calcium L-threonate effectively improved the structural integrity, thermal stability, and calcium bioavailability of fish gelatin-based jelly, while maintaining acceptable sensory qualities, highlighting its potential as a functional calcium-fortified confectionery product.
{"title":"Physicochemical, Sensorial and Calcium Bioavailability of Jelly Prepared Using Fish Gelatin in Combination with Furcellaran and Calcium L-Threonate.","authors":"Tanyamon Petcharat, Manat Chaijan, Sylvia Indriani, Supatra Karnjanapratum, Nilesh Nirmal, Jaspreet Singh, Ihlana Nairfana, Sitthipong Nalinanon","doi":"10.3390/gels12010026","DOIUrl":"10.3390/gels12010026","url":null,"abstract":"<p><p>Confectionery products, specifically jelly and gummy, require optimized structural, thermal, and nutritional properties for functionality and consumer acceptance. This study investigated the impact of furcellaran (FUR) and calcium L-threonate (Ca) on the physicochemical and the sensory properties of fish gelatin-based jelly (JFG). Furcellaran modestly enhanced gel strength and hardness, while its combination with calcium L-threonate produced synergistic improvements, with JFG-FUR-Ca achieving the highest gel strength (947.63 g) and hardness (78.14 N). Microstructural and intermolecular force analyses indicated that Ca<sup>2+</sup> bridging between gelatin and furcellaran promoted ionic and hydrogen bonding, forming a dense and thermostable network. The combined incorporation of furcellaran and calcium L-threonate enhanced the rheological properties while preserving low syneresis. Sensory evaluation revealed minor reductions; however, overall acceptability was higher than 7. Calcium bioavailability after digestion through the gastrointestinal tract model remained high (70-80%), confirming effective calcium fortification. The synergistic incorporation of furcellaran and calcium L-threonate effectively improved the structural integrity, thermal stability, and calcium bioavailability of fish gelatin-based jelly, while maintaining acceptable sensory qualities, highlighting its potential as a functional calcium-fortified confectionery product.</p>","PeriodicalId":12506,"journal":{"name":"Gels","volume":"12 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12840786/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146051478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tamara Erceg, Miloš Radosavljević, Milorad Miljić, Aleksandra Cvetanović Kljakić, Sebastian Baloš, Katarina Mišković Špoljarić, Ivan Ćorić, Ljubica Glavaš-Obrovac, Aleksandra Torbica
In this study, dextran-based hydrogels were synthesized in dimethyl sulfoxide via free-radical polymerization with three structurally different crosslinking agents: divinyl benzene (DVB), diethylene glycol diacrylate (DEGDA), and 4,4'-di(methacryloylamino)azobenzene (DMAAazoB). Their morphology, swelling ability, mechanical properties, and potential for controlled release of the model substance (uracil) were examined, with the results showing that the chemical structure and chain length of the crosslinking agents significantly influence the structural and functional properties of hydrogels. Hydrogels crosslinked with DMAAazoB showed the highest swelling ability at pH 3 and pH 6 (2552 and 1696%, respectively), associated with protonation effects and sponge-like morphology, while simultaneously showing the lowest mechanical strength (20 and 47 MPa). In vitro simulations of gastrointestinal digestion showed that uracil was not released in the gastric phase, while in the intestinal environment, the release was significant, especially in Dex-DMAAzoB hydrogels (88.52%). The absence of azoreductases in the simulated system indicates that the release of the drug in real conditions would likely be even more pronounced. The Dex-DAAazoB hydrogel exhibited a slight antibacterial effect, producing inhibition zones of 8 and 7 mm against Escherichia coli ATCC 8739 and Staphylococcus epidermidis ATCC 12228, respectively. In contrast, the remaining hydrogel formulations showed no detectable antibacterial activity toward either bacterial strain, indicating their microbiological inertness and supporting their suitability as carrier matrices for antitumor drug delivery in colorectal cancer therapy. The obtained results confirm that azo-crosslinked dextran hydrogels, with an optimized amount of crosslinking agent, are promising carriers for the targeted and controlled delivery of antitumor drugs to the colorectal region.
{"title":"Part II: The Influence of Crosslinking Agents on the Properties and Colon-Targeted Drug Delivery Efficacy of Dextran-Based Hydrogels.","authors":"Tamara Erceg, Miloš Radosavljević, Milorad Miljić, Aleksandra Cvetanović Kljakić, Sebastian Baloš, Katarina Mišković Špoljarić, Ivan Ćorić, Ljubica Glavaš-Obrovac, Aleksandra Torbica","doi":"10.3390/gels12010025","DOIUrl":"10.3390/gels12010025","url":null,"abstract":"<p><p>In this study, dextran-based hydrogels were synthesized in dimethyl sulfoxide via free-radical polymerization with three structurally different crosslinking agents: divinyl benzene (DVB), diethylene glycol diacrylate (DEGDA), and 4,4'-di(methacryloylamino)azobenzene (DMAAazoB). Their morphology, swelling ability, mechanical properties, and potential for controlled release of the model substance (uracil) were examined, with the results showing that the chemical structure and chain length of the crosslinking agents significantly influence the structural and functional properties of hydrogels. Hydrogels crosslinked with DMAAazoB showed the highest swelling ability at pH 3 and pH 6 (2552 and 1696%, respectively), associated with protonation effects and sponge-like morphology, while simultaneously showing the lowest mechanical strength (20 and 47 MPa). In vitro simulations of gastrointestinal digestion showed that uracil was not released in the gastric phase, while in the intestinal environment, the release was significant, especially in Dex-DMAAzoB hydrogels (88.52%). The absence of azoreductases in the simulated system indicates that the release of the drug in real conditions would likely be even more pronounced. The Dex-DAAazoB hydrogel exhibited a slight antibacterial effect, producing inhibition zones of 8 and 7 mm against <i>Escherichia coli</i> ATCC 8739 and <i>Staphylococcus epidermidis</i> ATCC 12228, respectively. In contrast, the remaining hydrogel formulations showed no detectable antibacterial activity toward either bacterial strain, indicating their microbiological inertness and supporting their suitability as carrier matrices for antitumor drug delivery in colorectal cancer therapy. The obtained results confirm that azo-crosslinked dextran hydrogels, with an optimized amount of crosslinking agent, are promising carriers for the targeted and controlled delivery of antitumor drugs to the colorectal region.</p>","PeriodicalId":12506,"journal":{"name":"Gels","volume":"12 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12841459/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146051512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sanazar Kadyr, Bakhytbol Khumyrzakh, Swera Naz, Albina Abdossova, Bota Askarbek, Dilhan M Kalyon, Zhe Liu, Cevat Erisken
The osteochondral interface (OCI) is a structurally and functionally complex tissue whose degeneration or injury often results in poor healing and joint dysfunction due to its avascular and hypocellular nature. Conventional surgical treatments remain suboptimal, prompting growing interest in regenerative approaches, particularly with the utilization of hydrogel-based biomaterials that can mimic the extracellular matrix and support osteochondral regeneration. This study reviewed types of hydrogels, scaffold processing techniques, and animal models for OCI regeneration. Our search demonstrated that gelatin, alginate, chitosan, and hyaluronic acid were the most frequently investigated hydrogels. Layered constructs dominated current scaffold designs, while advanced methods such as 3D printing and extrusion demonstrated unique potential to create graded architectures resembling the native OCI. Rabbits were the most widely used in vivo models, though translation will require larger animal studies with clinically relevant defect sizes. Future efforts should focus on developing mechanically reinforced, biologically active, and continuously graded hydrogels, supported by standardized preclinical validation in large-animal models, to accelerate translation toward clinical solutions for osteochondral regeneration.
{"title":"Hydrogels for Osteochondral Interface Regeneration: Biomaterial Types, Processes, and Animal Models.","authors":"Sanazar Kadyr, Bakhytbol Khumyrzakh, Swera Naz, Albina Abdossova, Bota Askarbek, Dilhan M Kalyon, Zhe Liu, Cevat Erisken","doi":"10.3390/gels12010024","DOIUrl":"10.3390/gels12010024","url":null,"abstract":"<p><p>The osteochondral interface (OCI) is a structurally and functionally complex tissue whose degeneration or injury often results in poor healing and joint dysfunction due to its avascular and hypocellular nature. Conventional surgical treatments remain suboptimal, prompting growing interest in regenerative approaches, particularly with the utilization of hydrogel-based biomaterials that can mimic the extracellular matrix and support osteochondral regeneration. This study reviewed types of hydrogels, scaffold processing techniques, and animal models for OCI regeneration. Our search demonstrated that gelatin, alginate, chitosan, and hyaluronic acid were the most frequently investigated hydrogels. Layered constructs dominated current scaffold designs, while advanced methods such as 3D printing and extrusion demonstrated unique potential to create graded architectures resembling the native OCI. Rabbits were the most widely used in vivo models, though translation will require larger animal studies with clinically relevant defect sizes. Future efforts should focus on developing mechanically reinforced, biologically active, and continuously graded hydrogels, supported by standardized preclinical validation in large-animal models, to accelerate translation toward clinical solutions for osteochondral regeneration.</p>","PeriodicalId":12506,"journal":{"name":"Gels","volume":"12 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12841089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146051483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xushuang Jia, Dongmei Fan, Zhuoya Yang, Junjie Chang, Qi Wang, Xiaohan Cui, Da Liu, Ning Cui, Ye Jin
Disorders of skin wound healing and the repair of full-thickness skin defects remain significant clinical challenges. Natural polysaccharide-based hydrogels, with their excellent biocompatibility, tunable degradability, and multifunctional properties (e.g., antibacterial, antioxidant, and pro-angiogenic), have emerged as key materials for designing wound dressings and skin tissue engineering scaffolds. This review systematically summarizes recent advances in polysaccharide hydrogels-including chitosan, hyaluronic acid, and alginate-focusing on material types, crosslinking strategies, and functional modifications, with particular emphasis on their dual applications in wound healing (acute and chronic wounds) and skin tissue engineering. In wound healing, these hydrogels regulate the microenvironment through multiple mechanisms, including anti-inflammatory, antioxidant, pro-angiogenic, and immunomodulatory effects. In skin tissue engineering, their three-dimensional porous structures mimic the extracellular matrix, supporting cell adhesion, proliferation, and tissue regeneration. Finally, we discuss the challenges and future prospects for the clinical translation and commercialization of natural polysaccharide hydrogels.
{"title":"Research Progress of Natural Polysaccharide-Based Hydrogels in Skin Tissue Regeneration.","authors":"Xushuang Jia, Dongmei Fan, Zhuoya Yang, Junjie Chang, Qi Wang, Xiaohan Cui, Da Liu, Ning Cui, Ye Jin","doi":"10.3390/gels12010021","DOIUrl":"10.3390/gels12010021","url":null,"abstract":"<p><p>Disorders of skin wound healing and the repair of full-thickness skin defects remain significant clinical challenges. Natural polysaccharide-based hydrogels, with their excellent biocompatibility, tunable degradability, and multifunctional properties (e.g., antibacterial, antioxidant, and pro-angiogenic), have emerged as key materials for designing wound dressings and skin tissue engineering scaffolds. This review systematically summarizes recent advances in polysaccharide hydrogels-including chitosan, hyaluronic acid, and alginate-focusing on material types, crosslinking strategies, and functional modifications, with particular emphasis on their dual applications in wound healing (acute and chronic wounds) and skin tissue engineering. In wound healing, these hydrogels regulate the microenvironment through multiple mechanisms, including anti-inflammatory, antioxidant, pro-angiogenic, and immunomodulatory effects. In skin tissue engineering, their three-dimensional porous structures mimic the extracellular matrix, supporting cell adhesion, proliferation, and tissue regeneration. Finally, we discuss the challenges and future prospects for the clinical translation and commercialization of natural polysaccharide hydrogels.</p>","PeriodicalId":12506,"journal":{"name":"Gels","volume":"12 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12840916/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146051473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Diana V Félix-Alcalá, Mirian A González-Ayón, Lizbeth A Manzanares-Guevara, Alexei F Licea-Navarro, Eugenio R Méndez, Angel Licea-Claverie
This study presents the development and evaluation of multifunctional, thermoresponsive nanogels based on poly(N-vinylcaprolactam-co-N-vinylpyrrolidone) (P(NVCL-co-NVP)) with a poly(ethylene glycol) methyl ether methacrylate (PEGMA) shell and galactose (GAL) targeting ligand for colon cancer therapy. The nanogels were engineered to encapsulate two chemotherapeutic agents, curcumin (CUR) and 5-fluorouracil (5-FU), along with gold nanorods (GNRDs) to enable a synergistic chemo-photothermal treatment approach. These nanogels exhibit excellent biocompatibility and stability and a temperature-responsive drug release profile, leveraging the volume-phase transition temperature (VPTT) of the polymer network for controlled delivery. The inclusion of GNRDs permits efficient photothermal conversion upon near-infrared (NIR) irradiation, resulting in localized hyperthermia and, theoretically, improved cytotoxicity when combined with chemotherapeutics. In vitro studies on colon cancer cells demonstrated enhanced drug accumulation, photothermal ablation when the GNRD concentration was above a threshold, and superior antitumor efficacy of the CUR/5-FU-loaded systems. The effectiveness of the chemo/photothermal combination could not be demonstrated, possibly due to the low concentration of GNRD and/or the use of a single irradiation step only. This work highlights the potential of P(NVCL-co-NVP):PEGMA:GAL nanogels as versatile nanocarriers for combined chemo-photothermal therapy. A more effective chemo/photothermal combination for colon cancer treatment can be achieved through the optimization of the GNRD loading/irradiation dosage.
本研究介绍了基于聚(n -乙烯基己内酰胺-co- n -乙烯基吡咯烷酮)(P(NVCL-co-NVP))和聚(乙二醇)甲基丙烯酸甲酯(PEGMA)外壳和半乳糖(GAL)靶向配体的多功能热响应纳米凝胶的开发和评价。纳米凝胶被设计成包封两种化疗药物,姜黄素(CUR)和5-氟尿嘧啶(5-FU),以及金纳米棒(gnrd),以实现协同化学光热治疗方法。这些纳米凝胶表现出优异的生物相容性和稳定性,并具有温度响应的药物释放特征,利用聚合物网络的体积相变温度(VPTT)进行控制递送。gnrd的包含允许近红外(NIR)照射下的有效光热转换,导致局部热疗,并且在理论上,与化疗药物联合使用时改善细胞毒性。对结肠癌细胞的体外研究表明,当GNRD浓度高于阈值时,药物积累增强,光热消融,并且负载CUR/5- fu系统具有优越的抗肿瘤功效。无法证明化学/光热组合的有效性,可能是由于GNRD浓度低和/或仅使用单一照射步骤。这项工作强调了P(NVCL-co-NVP):PEGMA:GAL纳米凝胶作为化学-光热联合治疗的多功能纳米载体的潜力。通过优化GNRD负载/照射剂量,可以实现更有效的化疗/光热联合治疗结肠癌。
{"title":"PNVCL-Based Multifunctional Nanogels Loaded with Curcumin, 5-Fluorouracil, and Gold Nanorods: Their Performance in Colon Cancer Cells.","authors":"Diana V Félix-Alcalá, Mirian A González-Ayón, Lizbeth A Manzanares-Guevara, Alexei F Licea-Navarro, Eugenio R Méndez, Angel Licea-Claverie","doi":"10.3390/gels12010023","DOIUrl":"10.3390/gels12010023","url":null,"abstract":"<p><p>This study presents the development and evaluation of multifunctional, thermoresponsive nanogels based on poly(<i>N</i>-vinylcaprolactam-<i>co-N</i>-vinylpyrrolidone) (P(NVCL-<i>co</i>-NVP)) with a poly(ethylene glycol) methyl ether methacrylate (PEGMA) shell and galactose (GAL) targeting ligand for colon cancer therapy. The nanogels were engineered to encapsulate two chemotherapeutic agents, curcumin (CUR) and 5-fluorouracil (5-FU), along with gold nanorods (GNRDs) to enable a synergistic chemo-photothermal treatment approach. These nanogels exhibit excellent biocompatibility and stability and a temperature-responsive drug release profile, leveraging the volume-phase transition temperature (VPTT) of the polymer network for controlled delivery. The inclusion of GNRDs permits efficient photothermal conversion upon near-infrared (NIR) irradiation, resulting in localized hyperthermia and, theoretically, improved cytotoxicity when combined with chemotherapeutics. In vitro studies on colon cancer cells demonstrated enhanced drug accumulation, photothermal ablation when the GNRD concentration was above a threshold, and superior antitumor efficacy of the CUR/5-FU-loaded systems. The effectiveness of the chemo/photothermal combination could not be demonstrated, possibly due to the low concentration of GNRD and/or the use of a single irradiation step only. This work highlights the potential of P(NVCL-<i>co</i>-NVP):PEGMA:GAL nanogels as versatile nanocarriers for combined chemo-photothermal therapy. A more effective chemo/photothermal combination for colon cancer treatment can be achieved through the optimization of the GNRD loading/irradiation dosage.</p>","PeriodicalId":12506,"journal":{"name":"Gels","volume":"12 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12841463/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146051543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gel-based depots are increasingly recognized as platforms to extend the intratissue residence of local anesthetics (LAs) while reducing systemic exposure. Hydrogels, organogels, and emerging bigels represent three distinct architectures defined by their continuous phases and drug-matrix interactions. Hydrogels provide hydrated polymer networks with predictable injectability, tunable degradation, and diffusion- or stimulus-responsive release, enabling sustained analgesia in perineural, peri-incisional, intra-articular, and implant-adjacent settings. Organogels, formed by supramolecular assembly of low-molecular-weight gelators in lipids or semi-polar solvents, strongly solubilize lipophilic LA bases and enhance barrier partitioning, making them suitable for dermal, transdermal, and mucosal applications in outpatient or chronic pain care. Bigels integrate aqueous and lipid domains within biphasic matrices, improving rheology, spreadability, and dual-solubilization capacity, although their use in LA delivery remains at the formulation stage, with no validated in vivo pharmacology. This narrative review synthesizes the design principles, release mechanisms, and translational evidence across these platforms, highlighting domain-specific advantages and barriers related to mechanical robustness, sterilization, reproducibility, and regulatory feasibility. We propose a platform-level framework in which depot selection is aligned with LA chemistry, anatomical context, and clinical objectives to guide the development of workflow-compatible next-generation LA depots.
{"title":"Hydrogels and Organogels for Local Anesthetic Delivery: Advances, Challenges, and Translational Perspectives.","authors":"Jong-Woan Kim, Jin-Oh Jeong, Hoon Choi","doi":"10.3390/gels12010022","DOIUrl":"10.3390/gels12010022","url":null,"abstract":"<p><p>Gel-based depots are increasingly recognized as platforms to extend the intratissue residence of local anesthetics (LAs) while reducing systemic exposure. Hydrogels, organogels, and emerging bigels represent three distinct architectures defined by their continuous phases and drug-matrix interactions. Hydrogels provide hydrated polymer networks with predictable injectability, tunable degradation, and diffusion- or stimulus-responsive release, enabling sustained analgesia in perineural, peri-incisional, intra-articular, and implant-adjacent settings. Organogels, formed by supramolecular assembly of low-molecular-weight gelators in lipids or semi-polar solvents, strongly solubilize lipophilic LA bases and enhance barrier partitioning, making them suitable for dermal, transdermal, and mucosal applications in outpatient or chronic pain care. Bigels integrate aqueous and lipid domains within biphasic matrices, improving rheology, spreadability, and dual-solubilization capacity, although their use in LA delivery remains at the formulation stage, with no validated in vivo pharmacology. This narrative review synthesizes the design principles, release mechanisms, and translational evidence across these platforms, highlighting domain-specific advantages and barriers related to mechanical robustness, sterilization, reproducibility, and regulatory feasibility. We propose a platform-level framework in which depot selection is aligned with LA chemistry, anatomical context, and clinical objectives to guide the development of workflow-compatible next-generation LA depots.</p>","PeriodicalId":12506,"journal":{"name":"Gels","volume":"12 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12841318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146051398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jun An, Liyou Zheng, Shuzhen Xuan, Xinyi He, Tao Yang
As a step towards the substitution of saturated fats with camellia oil in foods, a camellia oil-based oleogel was prepared using a walnut protein isolate-chitosan (WPI-CS) composite via an emulsion template method. The preparation process, structural characteristics, and stability of the oleogel were systematically analyzed. Our findings showed that varying the ratio of WPI-CS to camellia oil (CO) effectively regulated the emulsion particle size, zeta potential, and viscosity, thereby subsequently influencing the oil-holding capacity (OHC), rheological properties, and thermal stability of the oleogel. When the WPI-CS:CO ratio was 13:7, the oleogel exhibited superior performance, including relatively high OHC, improved rheological properties, and excellent thermal stability. In addition, the OHC of the oleogel varied significantly with temperature, and high oxidative stability was observed at WPI-CS ratios such as 13:7-10:10. Application tests in cake formulations demonstrated that the oleogel has potential as a partial butter replacement. This study provides a theoretical basis for the construction of WPI-based oleogels and offers new insights for the development of healthy fat substitutes.
{"title":"Camellia Oil Oleogels Structured with Walnut Protein-Chitosan Complexes: Preparation, Characterization, and Potential Applications.","authors":"Jun An, Liyou Zheng, Shuzhen Xuan, Xinyi He, Tao Yang","doi":"10.3390/gels12010020","DOIUrl":"10.3390/gels12010020","url":null,"abstract":"<p><p>As a step towards the substitution of saturated fats with camellia oil in foods, a camellia oil-based oleogel was prepared using a walnut protein isolate-chitosan (WPI-CS) composite via an emulsion template method. The preparation process, structural characteristics, and stability of the oleogel were systematically analyzed. Our findings showed that varying the ratio of WPI-CS to camellia oil (CO) effectively regulated the emulsion particle size, zeta potential, and viscosity, thereby subsequently influencing the oil-holding capacity (OHC), rheological properties, and thermal stability of the oleogel. When the WPI-CS:CO ratio was 13:7, the oleogel exhibited superior performance, including relatively high OHC, improved rheological properties, and excellent thermal stability. In addition, the OHC of the oleogel varied significantly with temperature, and high oxidative stability was observed at WPI-CS ratios such as 13:7-10:10. Application tests in cake formulations demonstrated that the oleogel has potential as a partial butter replacement. This study provides a theoretical basis for the construction of WPI-based oleogels and offers new insights for the development of healthy fat substitutes.</p>","PeriodicalId":12506,"journal":{"name":"Gels","volume":"12 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12841583/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146051353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Three-dimensional (3D) cell culture systems require biocompatible carriers that provide both structural support and efficient mass transport. Conventional alginate-based encapsulation systems suffer from poor molecular diffusion, lack of cell adhesion motifs, and structural instability under physiological conditions. Here, we report the first development of hollow-shell collagen microcapsules (CMCs) fabricated via a gelatin sacrificial template approach that overcomes these critical limitations. The hollow architecture combined with collagen's intrinsic bioactivity achieved 2.5-fold enhancement in molecular permeability compared to conventional alginate beads, while maintaining structural integrity for 14 days versus 3-day collapse of alginate controls. NIH 3T3 fibroblasts encapsulated within CMCs demonstrated superior proliferation and formed tissue-like multilayered structures with extensive extracellular matrix deposition. This platform represents a significant advance in 3D cell culture technology, providing a biologically functional microenvironment with enhanced mass transport properties for applications in tissue engineering and regenerative medicine.
{"title":"Development and Characterization of Hollow-Shell Collagen Microcapsules for Three-Dimensional Cell Culture.","authors":"Yusuke Chiwata, Shigehisa Aoki, Takehisa Sakumoto, Takayuki Narita","doi":"10.3390/gels12010015","DOIUrl":"10.3390/gels12010015","url":null,"abstract":"<p><p>Three-dimensional (3D) cell culture systems require biocompatible carriers that provide both structural support and efficient mass transport. Conventional alginate-based encapsulation systems suffer from poor molecular diffusion, lack of cell adhesion motifs, and structural instability under physiological conditions. Here, we report the first development of hollow-shell collagen microcapsules (CMCs) fabricated via a gelatin sacrificial template approach that overcomes these critical limitations. The hollow architecture combined with collagen's intrinsic bioactivity achieved 2.5-fold enhancement in molecular permeability compared to conventional alginate beads, while maintaining structural integrity for 14 days versus 3-day collapse of alginate controls. NIH 3T3 fibroblasts encapsulated within CMCs demonstrated superior proliferation and formed tissue-like multilayered structures with extensive extracellular matrix deposition. This platform represents a significant advance in 3D cell culture technology, providing a biologically functional microenvironment with enhanced mass transport properties for applications in tissue engineering and regenerative medicine.</p>","PeriodicalId":12506,"journal":{"name":"Gels","volume":"12 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12840939/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146051355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Natalia Menshutina, Eldar Golubev, Andrey Abramov, Pavel Tsygankov
Alginate aerogels are attractive candidates for biomedical scaffolds because they combine high mesoporosity with biocompatibility and can be processed into open, interconnected macroporous networks suitable for tissue engineering. Here, we systematically investigate how CO2-induced foaming parameters govern the hierarchical pore structure of alginate aerogels produced by subsequent supercritical CO2 drying. Sodium alginate-CaCO3 suspensions are foamed in a CO2 atmosphere at 50 or 100 bar, depressurization rates of 50 or 0.05 bar·s-1, temperatures of 5 or 25 °C, and, optionally, under pulsed pressure or with Pluronic F-68 as a surfactant. The resulting gels are dried using supercritical CO2 and characterized by micro-computed tomography and N2 sorption. High pressure combined with slow depressurization (100 bar, 0.05 bar·s-1) yields a homogeneous macroporous network with pores predominantly in the 200-500 µm range and a mesoporous texture with 15-35 nm pores, whereas fast depressurization promotes bubble coalescence and the appearance of large (>2100 µm) macropores and a broader mesopore distribution. Lowering the temperature, applying pulsed pressure, and adding surfactant enable further tuning of macropore size and connectivity with a limited impact on mesoporosity. Interpretation in terms of Peclet and Deborah numbers links processing conditions to non-equilibrium mass transfer and gel viscoelasticity, providing a physically grounded map for designing hierarchically porous alginate aerogel scaffolds for biomedical applications.
海藻酸盐气凝胶是生物医学支架的有吸引力的候选者,因为它们结合了高介孔性和生物相容性,可以加工成适合组织工程的开放、相互连接的大孔网络。在这里,我们系统地研究了二氧化碳诱导的发泡参数如何控制随后超临界CO2干燥产生的海藻酸盐气凝胶的分层孔结构。海藻酸钠-碳酸钙悬浮液在50或100 bar的CO2气氛中发泡,减压速率为50或0.05 bar·s-1,温度为5或25℃,并可选择在脉冲压力下或以Pluronic F-68作为表面活性剂。所得凝胶用超临界CO2干燥,用微计算机断层扫描和N2吸附进行表征。高压与缓慢减压(100 bar, 0.05 bar·s-1)相结合,形成了均匀的大孔网络,孔隙主要分布在200-500µm范围内,具有15-35 nm的介孔结构,而快速减压促进了气泡聚并,出现了大(>2100µm)的大孔和更广泛的介孔分布。降低温度、施加脉冲压力和添加表面活性剂可以进一步调整大孔尺寸和连通性,同时对介孔的影响有限。根据Peclet和Deborah数字的解释,将加工条件与非平衡传质和凝胶粘弹性联系起来,为设计用于生物医学应用的分层多孔藻酸盐气凝胶支架提供了物理基础图。
{"title":"CO<sub>2</sub>-Induced Foaming and Gelation for the Fabrication of Macroporous Alginate Aerogel Scaffolds.","authors":"Natalia Menshutina, Eldar Golubev, Andrey Abramov, Pavel Tsygankov","doi":"10.3390/gels12010017","DOIUrl":"10.3390/gels12010017","url":null,"abstract":"<p><p>Alginate aerogels are attractive candidates for biomedical scaffolds because they combine high mesoporosity with biocompatibility and can be processed into open, interconnected macroporous networks suitable for tissue engineering. Here, we systematically investigate how CO<sub>2</sub>-induced foaming parameters govern the hierarchical pore structure of alginate aerogels produced by subsequent supercritical CO<sub>2</sub> drying. Sodium alginate-CaCO<sub>3</sub> suspensions are foamed in a CO<sub>2</sub> atmosphere at 50 or 100 bar, depressurization rates of 50 or 0.05 bar·s<sup>-1</sup>, temperatures of 5 or 25 °C, and, optionally, under pulsed pressure or with Pluronic F-68 as a surfactant. The resulting gels are dried using supercritical CO<sub>2</sub> and characterized by micro-computed tomography and N<sub>2</sub> sorption. High pressure combined with slow depressurization (100 bar, 0.05 bar·s<sup>-1</sup>) yields a homogeneous macroporous network with pores predominantly in the 200-500 µm range and a mesoporous texture with 15-35 nm pores, whereas fast depressurization promotes bubble coalescence and the appearance of large (>2100 µm) macropores and a broader mesopore distribution. Lowering the temperature, applying pulsed pressure, and adding surfactant enable further tuning of macropore size and connectivity with a limited impact on mesoporosity. Interpretation in terms of Peclet and Deborah numbers links processing conditions to non-equilibrium mass transfer and gel viscoelasticity, providing a physically grounded map for designing hierarchically porous alginate aerogel scaffolds for biomedical applications.</p>","PeriodicalId":12506,"journal":{"name":"Gels","volume":"12 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12841402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146051298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}