Many gastropods secrete mucus, which is more viscous and adhesive than the common trail mucus. The primary biochemical distinction between the two types of mucus is the higher protein content of the adhesive mucus. Not enough is known about the function of each of these proteins. In the current study, two of such mucus proteins were isolated from the adhesive mucus of the land snail Macrochlamys indica. In an attempt to imitate the structure of the mucus, these proteins were mixed with commercial hyaluronic acid (HA). The resultant hydrogel was found to have adhesive properties. A cell viability assay revealed that each of the hydrogel components and their mixtures were biologically safe and compatible. The in vitro cell migration assay showed better wound closure in case of the mucus protein as compared to HA, which is already known for its wound healing properties. The hydrogel was used for incision wound healing in mice, followed by histological staining. The result showed faster healing when compared to that of commercial wound healing ointment. In conclusion, this study presents a wound repair material, formulated from snail protein and HA and useful as an adhesive wound dressing with healing effects.
{"title":"Adhesive and Wound Healing, Dual Active Hydrogel with Snail Mucus Proteins","authors":"Oindrila Das, , , Janu Newar, , , Suchanda Verma, , , Gourabamani Swalsingh, , , Aleena Das, , , K. Sony Reddy, , , Naresh Chandra Bal, , and , Archana Ghatak*, ","doi":"10.1021/acsabm.5c01923","DOIUrl":"10.1021/acsabm.5c01923","url":null,"abstract":"<p >Many gastropods secrete mucus, which is more viscous and adhesive than the common trail mucus. The primary biochemical distinction between the two types of mucus is the higher protein content of the adhesive mucus. Not enough is known about the function of each of these proteins. In the current study, two of such mucus proteins were isolated from the adhesive mucus of the land snail <i>Macrochlamys indica</i>. In an attempt to imitate the structure of the mucus, these proteins were mixed with commercial hyaluronic acid (HA). The resultant hydrogel was found to have adhesive properties. A cell viability assay revealed that each of the hydrogel components and their mixtures were biologically safe and compatible. The <i>in vitro</i> cell migration assay showed better wound closure in case of the mucus protein as compared to HA, which is already known for its wound healing properties. The hydrogel was used for incision wound healing in mice, followed by histological staining. The result showed faster healing when compared to that of commercial wound healing ointment. In conclusion, this study presents a wound repair material, formulated from snail protein and HA and useful as an adhesive wound dressing with healing effects.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"8 12","pages":"11248–11261"},"PeriodicalIF":4.7,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145511251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wasitha P. D. W. Thilakarathna, , , Emma G. Welshman, , , Namita Bhasin, , , William Austin, , , Jonah Glazebrook, , , Zeeshan Sheikh, , and , Vahid Adibnia*,
The enzymatic degradation of hyaluronic acid (HA) and carboxyl-modified chitosan (CC) polymers in aqueous dispersions can be controlled by dynamic covalent cross-linking. Unlike un-cross-linked HA, dynamic covalent cross-linking preserves the viscoelastic behavior of HA dispersions when exposed to hyaluronidase enzyme. Among the dynamic covalent cross-linked CC dispersions, only dispersions with degrees of deacetylation of 98% (CC98) partially upheld the viscoelastic behavior under lysozyme-mediated degradation. Overall, our results suggest that dynamic covalent cross-linking can produce injectable HA and CC dispersions with partial enzymatic degradation resistance.
{"title":"Controlling Enzymatic Degradation of Carboxyl-Modified Chitosan and Hyaluronic Acid Biopolymers Using Dynamic Covalent Cross-Linking","authors":"Wasitha P. D. W. Thilakarathna, , , Emma G. Welshman, , , Namita Bhasin, , , William Austin, , , Jonah Glazebrook, , , Zeeshan Sheikh, , and , Vahid Adibnia*, ","doi":"10.1021/acsabm.5c01744","DOIUrl":"10.1021/acsabm.5c01744","url":null,"abstract":"<p >The enzymatic degradation of hyaluronic acid (HA) and carboxyl-modified chitosan (CC) polymers in aqueous dispersions can be controlled by dynamic covalent cross-linking. Unlike un-cross-linked HA, dynamic covalent cross-linking preserves the viscoelastic behavior of HA dispersions when exposed to hyaluronidase enzyme. Among the dynamic covalent cross-linked CC dispersions, only dispersions with degrees of deacetylation of 98% (CC98) partially upheld the viscoelastic behavior under lysozyme-mediated degradation. Overall, our results suggest that dynamic covalent cross-linking can produce injectable HA and CC dispersions with partial enzymatic degradation resistance.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"8 12","pages":"10603–10609"},"PeriodicalIF":4.7,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145522516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Exosomes are nanoscale extracellular vesicles secreted by cells that possess molecular and pathological characteristics of their cellular origin. Acting as natural carriers, they efficiently transport a diverse cargo of biomolecules, including proteins, nucleic acids, lipids, metabolites, and small molecules facilitating highly specific intercellular communication. Owing to their inherent biocompatibility, target specificity, and cargo versatility, exosomes have emerged as one of the most promising platforms for diagnostic and therapeutic applications. This review comprehensively elaborates on intricate biogenesis and regulatory pathways governing exosome production, examines their structural composition and cargo loading preferences, and highlights emerging strategies to enhance their functional capabilities. We further explore recent breakthroughs at the intersection of exosome biology and nanotechnology, emphasizing their roles in maintaining cellular homeostasis, advancing disease diagnostics, and enabling targeted therapeutic delivery. Finally, we critically address current challenges and limitations in exosome research, offering insights into innovative solutions and future directions for their clinical translation.
{"title":"Engineered Exosomes as Programmable Nanocarriers for Targeted Theranostic and Translational Applications","authors":"Jugal Patil, , , Ankur Singh, , , Satyam Bhalerao, , , Syed Mudasir Ahmad, , , Rakesh M Rawal, , , Dhiraj Bhatia*, , and , Raghu Solanki*, ","doi":"10.1021/acsabm.5c01251","DOIUrl":"10.1021/acsabm.5c01251","url":null,"abstract":"<p >Exosomes are nanoscale extracellular vesicles secreted by cells that possess molecular and pathological characteristics of their cellular origin. Acting as natural carriers, they efficiently transport a diverse cargo of biomolecules, including proteins, nucleic acids, lipids, metabolites, and small molecules facilitating highly specific intercellular communication. Owing to their inherent biocompatibility, target specificity, and cargo versatility, exosomes have emerged as one of the most promising platforms for diagnostic and therapeutic applications. This review comprehensively elaborates on intricate biogenesis and regulatory pathways governing exosome production, examines their structural composition and cargo loading preferences, and highlights emerging strategies to enhance their functional capabilities. We further explore recent breakthroughs at the intersection of exosome biology and nanotechnology, emphasizing their roles in maintaining cellular homeostasis, advancing disease diagnostics, and enabling targeted therapeutic delivery. Finally, we critically address current challenges and limitations in exosome research, offering insights into innovative solutions and future directions for their clinical translation.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"8 12","pages":"10506–10529"},"PeriodicalIF":4.7,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145511254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Antibacterial resistance has become a growing global health challenge, with multidrug-resistant pathogens posing significant threats to public health. Traditional antibacterial agents often encounter problems such as high costs, low efficiency, poor antibacterial efficacy, and restricted biocompatibility. Thus, there is an urgent need to develop materials with enhanced antibacterial properties. In this study, CaCO3/C/PDA antibacterial composite was designed as a high-efficacy antibacterial agent against Gram-negative bacteria. Under near-infrared light irradiation (808 nm, 0.3 W/cm2, 4 min), the CaCO3/C/PDA0.2 exhibited satisfactory antibacterial activity against Gram-negative bacteria, including Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumonia, with sterilization rates of 91.7%, 98%, and 100%, respectively. The antibacterial mechanism could be attributed to the synergistic effects of photothermal and photodynamic therapy, where high temperatures can denature bacterial proteins and reactive oxygen species (ROS) may disrupt bacterial metabolism, ultimately leading to bacterial death. All of the experimental results confirmed that CaCO3/C/PDA is a promising antimicrobial agent for Gram-negative bacterial infections. In addition, the in vitro toxicity tests also confirmed that CaCO3/C/PDA possessed excellent biocompatibility. Overall, this work offers an approach and strategy for the development of next-generation antimicrobial materials with broad biomedical potential.
{"title":"Near-Infrared Light-Driven Photocatalytic Antibacterial Activity of CaCO3/C/PDA Nanocomposites against Gram-Negative Bacteria","authors":"Zhuoli Chen, , , Lingying Chen, , , Xiaozhi Zheng, , , Junlin Li, , , Jiankun Ding, , , Chen Cai, , and , Haiming Yu*, ","doi":"10.1021/acsabm.5c01840","DOIUrl":"10.1021/acsabm.5c01840","url":null,"abstract":"<p >Antibacterial resistance has become a growing global health challenge, with multidrug-resistant pathogens posing significant threats to public health. Traditional antibacterial agents often encounter problems such as high costs, low efficiency, poor antibacterial efficacy, and restricted biocompatibility. Thus, there is an urgent need to develop materials with enhanced antibacterial properties. In this study, CaCO<sub>3</sub>/C/PDA antibacterial composite was designed as a high-efficacy antibacterial agent against Gram-negative bacteria. Under near-infrared light irradiation (808 nm, 0.3 W/cm<sup>2</sup>, 4 min), the CaCO<sub>3</sub>/C/PDA<sup>0.2</sup> exhibited satisfactory antibacterial activity against Gram-negative bacteria, including <i>Escherichia coli</i>, <i>Pseudomonas aeruginosa</i>, and <i>Klebsiella pneumonia</i>, with sterilization rates of 91.7%, 98%, and 100%, respectively. The antibacterial mechanism could be attributed to the synergistic effects of photothermal and photodynamic therapy, where high temperatures can denature bacterial proteins and reactive oxygen species (ROS) may disrupt bacterial metabolism, ultimately leading to bacterial death. All of the experimental results confirmed that CaCO<sub>3</sub>/C/PDA is a promising antimicrobial agent for Gram-negative bacterial infections. In addition, the <i>in vitro</i> toxicity tests also confirmed that CaCO<sub>3</sub>/C/PDA possessed excellent biocompatibility. Overall, this work offers an approach and strategy for the development of next-generation antimicrobial materials with broad biomedical potential.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"8 12","pages":"11134–11144"},"PeriodicalIF":4.7,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145511212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Karla E. Cureño Hernandez, , , Jeonghun Lee, , , Zachary Cartwright, , , Sunghoon Kim, , and , Margarita Herrera-Alonso*,
Mucosal barriers protect epithelial tissues but limit the diffusion of therapeutic nanoparticles, posing a major challenge for transmucosal drug delivery. Surface chemistry plays a key role in navigating this barrier, where both mucoadhesive and mucopenetrating strategies have shown value. In this study, we demonstrate how combining zwitterionic and boronic acid functionalities enables the rational design of nanoparticles with tunable interactions toward mucus. Block copolymers of poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) and poly(carboxybetaine) (PMCB), with or without a terminal aminophenylboronic acid (APBA), were synthesized and used as nanoparticle stabilizers via flash nanoprecipitation using a multi-inlet vortex mixer. Nanoparticle permeation was examined in purified sheep small intestine mucus. PMPC-based nanoparticles exhibited superior transport compared to PMCB- and PEG-containing analogs. Increasing APBA density led to reduced permeation due to specific interactions with mucin-associated sialic acids; this effect was reversed upon preincubation with free sialic acid. Zeta potential analysis before and after mucus exposure confirmed preserved surface integrity regardless of APBA density. These findings highlight the ability to balance mucoadhesive and mucopenetrating properties via surface chemistry, offering a flexible platform for engineering nanoparticles optimized for mucus barrier traversal and downstream targeting in transmucosal drug delivery.
{"title":"Surface Chemistry-Driven Permeation of Nanoparticles Produced by Flash Nanoprecipitation through Mucus Barriers","authors":"Karla E. Cureño Hernandez, , , Jeonghun Lee, , , Zachary Cartwright, , , Sunghoon Kim, , and , Margarita Herrera-Alonso*, ","doi":"10.1021/acsabm.5c01736","DOIUrl":"10.1021/acsabm.5c01736","url":null,"abstract":"<p >Mucosal barriers protect epithelial tissues but limit the diffusion of therapeutic nanoparticles, posing a major challenge for transmucosal drug delivery. Surface chemistry plays a key role in navigating this barrier, where both mucoadhesive and mucopenetrating strategies have shown value. In this study, we demonstrate how combining zwitterionic and boronic acid functionalities enables the rational design of nanoparticles with tunable interactions toward mucus. Block copolymers of poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) and poly(carboxybetaine) (PMCB), with or without a terminal aminophenylboronic acid (APBA), were synthesized and used as nanoparticle stabilizers via flash nanoprecipitation using a multi-inlet vortex mixer. Nanoparticle permeation was examined in purified sheep small intestine mucus. PMPC-based nanoparticles exhibited superior transport compared to PMCB- and PEG-containing analogs. Increasing APBA density led to reduced permeation due to specific interactions with mucin-associated sialic acids; this effect was reversed upon preincubation with free sialic acid. Zeta potential analysis before and after mucus exposure confirmed preserved surface integrity regardless of APBA density. These findings highlight the ability to balance mucoadhesive and mucopenetrating properties via surface chemistry, offering a flexible platform for engineering nanoparticles optimized for mucus barrier traversal and downstream targeting in transmucosal drug delivery.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"8 12","pages":"11059–11074"},"PeriodicalIF":4.7,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145501200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Prajakta A. Mane, , , Rahul M. Sonavale*, , , Rohan Phatak, , , Nutan Shukla*, , , Zhengyou Li, , , Oleg E. Polozhentsev, , , Carol Cárdenas, , and , Sabrina Belbekhouche*,
Wound infections represent a significant global healthcare burden, often complicating healing processes and leading to increased morbidity. These infections vary in type, ranging from acute to chronic, surgical site infections, and pressure ulcers, each presenting distinct pathological and microbiological profiles. The primary causative agents include Gram-positive bacteria such as Staphylococcus aureus and Streptococcus pyogenes as well as Gram-negative pathogens such as Pseudomonas aeruginosa and Escherichia coli. Conventional treatment modalities largely rely on systemic or topical antibiotics, debridement of the wound, and antiseptics. However, rising antimicrobial resistance, slow tissue regeneration, and recurrent infections limit the efficacy of these approaches. Recent advances in nanotechnology- and biopolymer-based materials have enhanced wound care options. Biopolymers such as chitosan, alginate, and collagen are valued for their biocompatibility and biodegradability. Chitosan uniquely offers inherent antimicrobial activity, while collagen, alginate, and agarose mainly function as biocompatible scaffolds or drug delivery systems without significant antibacterial properties. When combined with metal nanoparticles, particularly silver, zinc oxide, and gold, these composites exhibit enhanced antibacterial activity, anti-inflammatory effects, and improved wound healing dynamics. Such nanocomposites can be engineered into films, hydrogels, and scaffolds that facilitate moisture retention, controlled drug release, and tissue regeneration, while minimizing cytotoxicity. The integration of nanotechnology with biopolymer science represents a paradigm shift in wound management strategies. This multidisciplinary approach not only addresses the limitations of conventional therapies but also offers tailored, responsive, and effective wound healing platforms. Continued research into the synergistic effects of nanoparticles and natural polymers is essential to fully realize their clinical potential. Ultimately, these innovations could transform wound care, offering patients faster recovery, reduced infection rates, and an improved quality of life. Additionally, hybrid nanocomposites such as hydroxyapatite-based systems have shown enhanced bioactive properties.
{"title":"Revolutionizing Wound Care: The Role of Nanotechnology and Biopolymer-Based Materials","authors":"Prajakta A. Mane, , , Rahul M. Sonavale*, , , Rohan Phatak, , , Nutan Shukla*, , , Zhengyou Li, , , Oleg E. Polozhentsev, , , Carol Cárdenas, , and , Sabrina Belbekhouche*, ","doi":"10.1021/acsabm.5c01412","DOIUrl":"10.1021/acsabm.5c01412","url":null,"abstract":"<p >Wound infections represent a significant global healthcare burden, often complicating healing processes and leading to increased morbidity. These infections vary in type, ranging from acute to chronic, surgical site infections, and pressure ulcers, each presenting distinct pathological and microbiological profiles. The primary causative agents include Gram-positive bacteria such as <i>Staphylococcus aureus</i> and <i>Streptococcus pyogenes</i> as well as Gram-negative pathogens such as <i>Pseudomonas aeruginosa</i> and <i>Escherichia coli</i>. Conventional treatment modalities largely rely on systemic or topical antibiotics, debridement of the wound, and antiseptics. However, rising antimicrobial resistance, slow tissue regeneration, and recurrent infections limit the efficacy of these approaches. Recent advances in nanotechnology- and biopolymer-based materials have enhanced wound care options. Biopolymers such as chitosan, alginate, and collagen are valued for their biocompatibility and biodegradability. Chitosan uniquely offers inherent antimicrobial activity, while collagen, alginate, and agarose mainly function as biocompatible scaffolds or drug delivery systems without significant antibacterial properties. When combined with metal nanoparticles, particularly silver, zinc oxide, and gold, these composites exhibit enhanced antibacterial activity, anti-inflammatory effects, and improved wound healing dynamics. Such nanocomposites can be engineered into films, hydrogels, and scaffolds that facilitate moisture retention, controlled drug release, and tissue regeneration, while minimizing cytotoxicity. The integration of nanotechnology with biopolymer science represents a paradigm shift in wound management strategies. This multidisciplinary approach not only addresses the limitations of conventional therapies but also offers tailored, responsive, and effective wound healing platforms. Continued research into the synergistic effects of nanoparticles and natural polymers is essential to fully realize their clinical potential. Ultimately, these innovations could transform wound care, offering patients faster recovery, reduced infection rates, and an improved quality of life. Additionally, hybrid nanocomposites such as hydroxyapatite-based systems have shown enhanced bioactive properties.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"8 12","pages":"10530–10548"},"PeriodicalIF":4.7,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145501237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Melanoma is a rare but highly aggressive form of skin cancer that can rapidly metastasize, leading to a significant mortality rate. A main challenge in chemotherapy is the lack of selectivity in drug delivery to tumor sites, which affects both tumor and healthy tissues. Developing drug delivery systems (DDS) capable of preferentially interacting with transporters expressed on cancer cells may help address this issue. Carbon dots (CDs) have emerged as promising tools for the advancement of DDS due to their distinctive fluorescent characteristics, good water solubility, biocompatibility, and straightforward fabrication. In this work, CDs were synthesized via a facile method and conjugated with tryptophan (Trp) to evaluate their potential application as a DDS in melanoma. The fabricated CDs were characterized for their size, surface charge, optical properties, functional groups, and elemental analysis. LAT1 expression was examined by immunofluorescence, confirming higher levels in SK-MEL-2 melanoma cells compared to HK-2 normal kidney cells. Biocompatibility was established before conjugating CDs with tryptophan (Trp), ditryptophan (di-Trp), and tritryptophan (tri-Trp) and assessing their size, functional groups, and optical characteristics. Cellular uptake studies showed preferential uptake of Trp-conjugated CDs in SK-MEL-2 cells over HK-2 cells, indicating that tri-Trp-CDs exhibited the highest uptake. Molecular dynamics simulations suggested potential CDs-LAT1 interactions via van der Waals and electrostatic interactions. Trp-conjugated CDs were biocompatible with both SK-MEL-2 and HK-2 cells and could be electrostatically loaded with doxorubicin (DOX), exhibiting enhanced cytotoxicity against SK-MEL-2 cells compared to DOX alone. A trend toward greater selectivity for SK-MEL-2 cells over normal cells was observed, with tri-Trp/DOX showing the most pronounced effect, possibly reflecting LAT1-1 mediated uptake. These findings suggest that Trp-modified CDs may serve as promising DDS candidates for melanoma treatment.
{"title":"Tryptophan-Conjugated Carbon Dots with Enhanced Cellular Uptake as a Potential Drug Delivery System for Melanoma","authors":"Nasrin Imumkachi, , , Pornpattra Rattanaseth, , , Sawinee Ngernpimai, , , Janpen Thonghlueng, , , Piyaporn Matulakul, , , Pakawat Toomjeen, , , Theerapong Puangmali, , , Raynoo Thanan, , , Tawut Rudtanatip, , , Natthida Weerapreeyakul, , and , Chadamas Sakonsinsiri*, ","doi":"10.1021/acsabm.5c01730","DOIUrl":"10.1021/acsabm.5c01730","url":null,"abstract":"<p >Melanoma is a rare but highly aggressive form of skin cancer that can rapidly metastasize, leading to a significant mortality rate. A main challenge in chemotherapy is the lack of selectivity in drug delivery to tumor sites, which affects both tumor and healthy tissues. Developing drug delivery systems (DDS) capable of preferentially interacting with transporters expressed on cancer cells may help address this issue. Carbon dots (CDs) have emerged as promising tools for the advancement of DDS due to their distinctive fluorescent characteristics, good water solubility, biocompatibility, and straightforward fabrication. In this work, CDs were synthesized via a facile method and conjugated with tryptophan (Trp) to evaluate their potential application as a DDS in melanoma. The fabricated CDs were characterized for their size, surface charge, optical properties, functional groups, and elemental analysis. LAT1 expression was examined by immunofluorescence, confirming higher levels in SK-MEL-2 melanoma cells compared to HK-2 normal kidney cells. Biocompatibility was established before conjugating CDs with tryptophan (Trp), ditryptophan (di-Trp), and tritryptophan (tri-Trp) and assessing their size, functional groups, and optical characteristics. Cellular uptake studies showed preferential uptake of Trp-conjugated CDs in SK-MEL-2 cells over HK-2 cells, indicating that tri-Trp-CDs exhibited the highest uptake. Molecular dynamics simulations suggested potential CDs-LAT1 interactions via van der Waals and electrostatic interactions. Trp-conjugated CDs were biocompatible with both SK-MEL-2 and HK-2 cells and could be electrostatically loaded with doxorubicin (DOX), exhibiting enhanced cytotoxicity against SK-MEL-2 cells compared to DOX alone. A trend toward greater selectivity for SK-MEL-2 cells over normal cells was observed, with tri-Trp/DOX showing the most pronounced effect, possibly reflecting LAT1-1 mediated uptake. These findings suggest that Trp-modified CDs may serve as promising DDS candidates for melanoma treatment.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"8 12","pages":"11047–11058"},"PeriodicalIF":4.7,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145511195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
David Naranjo, , , Juan Torras, , and , Jose García-Torres*,
The development of sustainable, soft, and recyclable materials for skin-integrated electronics is critical for advancing wearable health monitoring while minimizing electronic waste. Here, chitosan–agarose-based hydrogels integrated with poly(3,4-ethylenedioxythiophene):polystyrenesulfonate (PEDOT:PSS) are fabricated as recyclable, biocompatible, and thermoresponsive materials for flexible temperature sensors. The hydrogels are synthesized using a green and easy process, forming interpenetrated dual networks that exhibit high water content, mechanical compliance, and enhanced electroconductivity. Morphological analysis reveals highly porous interconnected structures, while Fourier transform infrared spectroscopy confirms the successful incorporation of PEDOT:PSS. The hydrogels display high swelling capacity, tunable mechanical properties within the physiological range of human skin, and enhanced electrochemical performance. The temperature-sensing capability of the hydrogels demonstrates a negative temperature coefficient of resistance (TCR) of up to −1.5% °C–1, outperforming similar hydrogel-based sensors while maintaining stability over repeated thermal cycles. Importantly, the hydrogels can be disassembled, reprocessed, and reused for multiple sensing cycles without significant loss of performance, demonstrating true recyclability and supporting circular material use in soft electronics. The convergence of natural biopolymers with conducting polymers within these hydrogels provides a promising platform for developing eco-friendly, flexible bioelectronic devices, aligning with the requirements of sustainable materials science while addressing the need for high-performance, soft temperature sensors for wearable healthcare applications.
{"title":"Soft, Sustainable, and Sensitive: Biopolymer-Based Hydrogels as Recyclable Temperature Sensors for Skin-Integrated Electronics","authors":"David Naranjo, , , Juan Torras, , and , Jose García-Torres*, ","doi":"10.1021/acsabm.5c01607","DOIUrl":"10.1021/acsabm.5c01607","url":null,"abstract":"<p >The development of sustainable, soft, and recyclable materials for skin-integrated electronics is critical for advancing wearable health monitoring while minimizing electronic waste. Here, chitosan–agarose-based hydrogels integrated with poly(3,4-ethylenedioxythiophene):polystyrenesulfonate (PEDOT:PSS) are fabricated as recyclable, biocompatible, and thermoresponsive materials for flexible temperature sensors. The hydrogels are synthesized using a green and easy process, forming interpenetrated dual networks that exhibit high water content, mechanical compliance, and enhanced electroconductivity. Morphological analysis reveals highly porous interconnected structures, while Fourier transform infrared spectroscopy confirms the successful incorporation of PEDOT:PSS. The hydrogels display high swelling capacity, tunable mechanical properties within the physiological range of human skin, and enhanced electrochemical performance. The temperature-sensing capability of the hydrogels demonstrates a negative temperature coefficient of resistance (TCR) of up to −1.5% °C<sup>–1</sup>, outperforming similar hydrogel-based sensors while maintaining stability over repeated thermal cycles. Importantly, the hydrogels can be disassembled, reprocessed, and reused for multiple sensing cycles without significant loss of performance, demonstrating true recyclability and supporting circular material use in soft electronics. The convergence of natural biopolymers with conducting polymers within these hydrogels provides a promising platform for developing eco-friendly, flexible bioelectronic devices, aligning with the requirements of sustainable materials science while addressing the need for high-performance, soft temperature sensors for wearable healthcare applications.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"8 12","pages":"10890–10902"},"PeriodicalIF":4.7,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acsabm.5c01607","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145511208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Efficient oral delivery and sustained viability of probiotics remain significant obstacles to the clinical translation of live biotherapeutics. Therefore, in this study, we developed self-assembling keratin hydrogels derived from feather waste using a disulfide shuffling strategy for probiotic encapsulation. This cost-effective and scalable approach substantially improved the gastrointestinal tolerance and oral bioavailability of multiple probiotics, including Escherichia coli Nissle 1917 (EcN), Bacillus licheniformis, Lactococcus lactis, and Bifidobacterium bifidum. To achieve site-specific release in the intestinal tract, EcN was engineered to express keratinase (EcNker), enabling hydrogel degradation in the gut. In dextran sulfate sodium-induced colitis model mice, hydrogel-encapsulated EcNker exhibited markedly superior therapeutic efficacy over unencapsulated probiotics, as indicated by the amelioration of clinical symptoms, restoration of colon histology, attenuation of intestinal apoptosis, and normalization of inflammatory cytokine profiles. Mechanistically, hydrogel-encapsulated EcNker treatment restored the gut barrier integrity by upregulating the tight junction protein levels, modulating gut microbiota by increasing the number of beneficial genera, and enhancing short-chain fatty acid production. Collectively, our findings highlight the potential of keratin hydrogels as universal biocompatible and efficient delivery platforms for orally engineered probiotics to treat colonic colitis and other diseases.
{"title":"Synergistic Therapeutic Efficacy of Engineered Probiotics Embedded in Self-Assembling Keratin Hydrogels for Ulcerative Colitis Treatment","authors":"Yijiao Wen, , , Chunhua Zhang, , , Xuanting Wang, , , Yi Shen, , , Huiwen Luo, , , Siyuan Liu, , , Famin Ke, , , Qin Wang*, , and , Xiaowei Gao*, ","doi":"10.1021/acsabm.5c01614","DOIUrl":"10.1021/acsabm.5c01614","url":null,"abstract":"<p >Efficient oral delivery and sustained viability of probiotics remain significant obstacles to the clinical translation of live biotherapeutics. Therefore, in this study, we developed self-assembling keratin hydrogels derived from feather waste using a disulfide shuffling strategy for probiotic encapsulation. This cost-effective and scalable approach substantially improved the gastrointestinal tolerance and oral bioavailability of multiple probiotics, including <i>Escherichia coli</i> Nissle 1917 (EcN), <i>Bacillus licheniformis</i>, <i>Lactococcus lactis</i>, and <i>Bifidobacterium bifidum</i>. To achieve site-specific release in the intestinal tract, EcN was engineered to express keratinase (EcNker), enabling hydrogel degradation in the gut. In dextran sulfate sodium-induced colitis model mice, hydrogel-encapsulated EcNker exhibited markedly superior therapeutic efficacy over unencapsulated probiotics, as indicated by the amelioration of clinical symptoms, restoration of colon histology, attenuation of intestinal apoptosis, and normalization of inflammatory cytokine profiles. Mechanistically, hydrogel-encapsulated EcNker treatment restored the gut barrier integrity by upregulating the tight junction protein levels, modulating gut microbiota by increasing the number of beneficial genera, and enhancing short-chain fatty acid production. Collectively, our findings highlight the potential of keratin hydrogels as universal biocompatible and efficient delivery platforms for orally engineered probiotics to treat colonic colitis and other diseases.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"8 12","pages":"10918–10932"},"PeriodicalIF":4.7,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145493808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Over the years, 3D printing has become a multidisciplinary research hotspot and state-of-the-art technology for developing bioinspired structures with intricate geometry, mechanical robustness and verified designs. However, the extrusion complexity of thermoplastic elastomeric filaments makes it challenging to design complex shapes in filament-based extrusion 3D printing. Herein, the paucity of low-modulus ethylene-co-vinyl acetate (EVA) polymer for the fabrication of bone tissue mimetic scaffolds was addressed by compounding with hydroxyapatite (HAP) and the effects of HAP incorporation on extrudability, printability, mechanical properties and osteoblast–material interactions were studied. The systematic optimization of printability and printing parameters enabled successful 3D printing of composite scaffolds with controlled deposition, pore geometry and architecture using a pellet-extrusion 3D printer. The die swell, unstable extrudate deposition and warpage of the EVA polymer melt subsided upon HAP addition. Confocal Raman microscopy and scanning electron microscopy (SEM) confirmed the uniform dispersion of HAP in EVA matrix, necessary to yield stable extrusion of the polymer melt. Dynamic mechanical analysis (DMA) revealed a 5-fold increase in storage modulus as well as a shift in Tg of the composites from −13°C to −9.8°C for 40 vol % HAP, confirming the possible polymer-HAP interactions. Biocompatibility studies demonstrated robust viability, proliferation and cellular integrity, especially in scaffolds with 40 vol % HAP. Moreover, F-actin staining of MG-63 cells revealed expanded cell pseudopods distributed evenly across the scaffold surface with a polygonal spreading pattern, confirming the cell adhesion and proliferation conducive for osteogenesis on the composite scaffolds. Osteogenic differentiation, as evidenced by ALP activity and Alizarin red S staining, indicated statistically higher levels of osteogenic-related factors and mineralization in composite scaffolds relative to neat EVA. These primary findings collectively support that the EVA-HAP composite, especially with 40 vol % HAP loading, provides a suitable microenvironment for osteoblast activities and is expected to promote bone tissue formation.
{"title":"3D Printable Ethylene-co-vinyl Acetate-Hydroxyapatite Composites for Bone Substitute Applications","authors":"Athira Murali, , , Shiny Velayudhan, , , Prakash Nair, , and , Ramesh Parameswaran*, ","doi":"10.1021/acsabm.5c01291","DOIUrl":"10.1021/acsabm.5c01291","url":null,"abstract":"<p >Over the years, 3D printing has become a multidisciplinary research hotspot and state-of-the-art technology for developing bioinspired structures with intricate geometry, mechanical robustness and verified designs. However, the extrusion complexity of thermoplastic elastomeric filaments makes it challenging to design complex shapes in filament-based extrusion 3D printing. Herein, the paucity of low-modulus ethylene-<i>co</i>-vinyl acetate (EVA) polymer for the fabrication of bone tissue mimetic scaffolds was addressed by compounding with hydroxyapatite (HAP) and the effects of HAP incorporation on extrudability, printability, mechanical properties and osteoblast–material interactions were studied. The systematic optimization of printability and printing parameters enabled successful 3D printing of composite scaffolds with controlled deposition, pore geometry and architecture using a pellet-extrusion 3D printer. The die swell, unstable extrudate deposition and warpage of the EVA polymer melt subsided upon HAP addition. Confocal Raman microscopy and scanning electron microscopy (SEM) confirmed the uniform dispersion of HAP in EVA matrix, necessary to yield stable extrusion of the polymer melt. Dynamic mechanical analysis (DMA) revealed a 5-fold increase in storage modulus as well as a shift in Tg of the composites from −13°C to −9.8°C for 40 vol % HAP, confirming the possible polymer-HAP interactions. Biocompatibility studies demonstrated robust viability, proliferation and cellular integrity, especially in scaffolds with 40 vol % HAP. Moreover, F-actin staining of MG-63 cells revealed expanded cell pseudopods distributed evenly across the scaffold surface with a polygonal spreading pattern, confirming the cell adhesion and proliferation conducive for osteogenesis on the composite scaffolds. Osteogenic differentiation, as evidenced by ALP activity and Alizarin red S staining, indicated statistically higher levels of osteogenic-related factors and mineralization in composite scaffolds relative to neat EVA. These primary findings collectively support that the EVA-HAP composite, especially with 40 vol % HAP loading, provides a suitable microenvironment for osteoblast activities and is expected to promote bone tissue formation.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"8 12","pages":"10690–10707"},"PeriodicalIF":4.7,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145493786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}