Pub Date : 2024-10-21Epub Date: 2024-09-29DOI: 10.1021/acsabm.4c01019
Muhammad Saqib Saif, Muhammad Waqas, Riaz Hussain, Muhammad Mahmood Ahmed, Tuba Tariq, Sana Batool, Qiang Liu, Ghazala Mustafa, Murtaza Hasan
Silymarin, an antioxidant, is locally used for kidney and heart ailments. However, its limited water solubility and less oral bioavailability limit its therapeutic efficiency. The present study investigated the enhancement of solubility and bioavailability of silymarin by loading it in Cordia myxa plant extract-coated zeolitic imidazole framework (CME@ZIF-8) against carbon tetrachloride (CCl4)-induced nephrotoxicity and cardiac toxicity in albino rats. The synthesized PEG-coated silymarin drug-loaded CME@ZIF-8 MOFs (PEG-Sily@CME@ZIF-8) were characterized by scanning electron microscopy, transmission electron microscopy, high-resolution transmission electron microscopy, energy dispersive X-ray spectroscopy, UV-visible spectroscopy, X-ray diffraction, Fourier transform infrared spectroscopy, thermogravimetric analysis, and zeta potential. The average crystal size of CME@ZIF-8 and PEG-Sily@CME@ZIF-8 was 12.69 and 16.81 nm, respectively. The silymarin drug loading percentage in PEG-Sily@CME@ZIF-8 was 33.05% (w/w). In the animal model with CCl4 treatment, different parameters like serum profile, enzymatic level, genotoxicity, and histopathology were assessed. Treatment with PEG-Sily@CME@ZIF-8 with different doses of 500, 1000, and 1500 μg/kg body weight efficiently ameliorated the alterations in the antioxidant defenses, biochemical parameters, and histopathological alterations and DNA damage in comparison to silymarin drug in a CCl4-induced toxicity rat model via alleviating the cellular abnormalities and attenuation of normal antioxidant enzymes levels. Moreover, the molecular mechanism of drug-silymarin interaction with the target protein was investigated. It involves the binding pockets of silymarin molecules with VEGFR, TNF-α, NLRP3, AT1R, NOX1, RIPK1, Caspase-3, CHOP, and MMP-9 proteins, elucidating the silymarin-protein interactions by the formation of hydrogen bonds and hydrophobic interactions. This study suggests that the nanodrug PEG-Sily@CME@ZIF-8 MOFs protect the kidneys and heart possibly by mitigating oxidative stress more efficiently than the conventional drug silymarin.
{"title":"Potential of CME@ZIF-8 MOF Nanoformulation: Smart Delivery of Silymarin for Enhanced Performance and Mechanism in Albino Rats.","authors":"Muhammad Saqib Saif, Muhammad Waqas, Riaz Hussain, Muhammad Mahmood Ahmed, Tuba Tariq, Sana Batool, Qiang Liu, Ghazala Mustafa, Murtaza Hasan","doi":"10.1021/acsabm.4c01019","DOIUrl":"10.1021/acsabm.4c01019","url":null,"abstract":"<p><p>Silymarin, an antioxidant, is locally used for kidney and heart ailments. However, its limited water solubility and less oral bioavailability limit its therapeutic efficiency. The present study investigated the enhancement of solubility and bioavailability of silymarin by loading it in <i>Cordia myxa</i> plant extract-coated zeolitic imidazole framework (CME@ZIF-8) against carbon tetrachloride (CCl<sub>4</sub>)-induced nephrotoxicity and cardiac toxicity in albino rats. The synthesized PEG-coated silymarin drug-loaded CME@ZIF-8 MOFs (PEG-Sily@CME@ZIF-8) were characterized by scanning electron microscopy, transmission electron microscopy, high-resolution transmission electron microscopy, energy dispersive X-ray spectroscopy, UV-visible spectroscopy, X-ray diffraction, Fourier transform infrared spectroscopy, thermogravimetric analysis, and zeta potential. The average crystal size of CME@ZIF-8 and PEG-Sily@CME@ZIF-8 was 12.69 and 16.81 nm, respectively. The silymarin drug loading percentage in PEG-Sily@CME@ZIF-8 was 33.05% (w/w). In the animal model with CCl<sub>4</sub> treatment, different parameters like serum profile, enzymatic level, genotoxicity, and histopathology were assessed. Treatment with PEG-Sily@CME@ZIF-8 with different doses of 500, 1000, and 1500 μg/kg body weight efficiently ameliorated the alterations in the antioxidant defenses, biochemical parameters, and histopathological alterations and DNA damage in comparison to silymarin drug in a CCl<sub>4</sub>-induced toxicity rat model via alleviating the cellular abnormalities and attenuation of normal antioxidant enzymes levels. Moreover, the molecular mechanism of drug-silymarin interaction with the target protein was investigated. It involves the binding pockets of silymarin molecules with VEGFR, TNF-α, NLRP3, AT1R, NOX1, RIPK1, Caspase-3, CHOP, and MMP-9 proteins, elucidating the silymarin-protein interactions by the formation of hydrogen bonds and hydrophobic interactions. This study suggests that the nanodrug PEG-Sily@CME@ZIF-8 MOFs protect the kidneys and heart possibly by mitigating oxidative stress more efficiently than the conventional drug silymarin.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142337209","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}
Excessive bleeding presents a grave risk to life, especially in scenarios involving deep wounds such as those inflicted by gunshots and accidental stabs. Despite advancements in wound care management, existing commercial hemostatic agents have limitations, necessitating the development of enhanced solutions. In this study, we developed cryogels using agarose and polydopamine microspheres as a hemostatic dressing to effectively manage profuse bleeding. The resulting cryogels demonstrated impressive attributes, such as high absorption capacity (>4000%), shape recovery ability, antioxidant properties, and excellent biocompatibility in mammalian cell lines. Particularly noteworthy was the rapid blood clotting observed in vitro, with the agarose/PDA cryogels achieving complete clotting within just 90 s. Subsequent validation in the rat trauma model further underscored their hemostatic efficacy, with clotting times of 40 and 53 s recorded in tail amputation and liver puncture models, respectively. The porous structure and hydrophilicity of the cryogels facilitated superior blood absorption and retention, while the amine groups of polydopamine played a pivotal role in enhancing blood clotting activity. This study represents a significant step forward in utilizing agarose/polydopamine cryogels as advanced materials for hemostatic wound dressings, promising an impactful contribution to wound therapy.
{"title":"Agarose Cryogels Loaded with Polydopamine Microspheres for Sustainable Wound Care with Enhanced Hemostatic and Antioxidant Properties.","authors":"Kaushal R Shakya, Nasim Mansoori, Anmol Anand, Vijay Sharma, Vivek Verma","doi":"10.1021/acsabm.4c00945","DOIUrl":"10.1021/acsabm.4c00945","url":null,"abstract":"<p><p>Excessive bleeding presents a grave risk to life, especially in scenarios involving deep wounds such as those inflicted by gunshots and accidental stabs. Despite advancements in wound care management, existing commercial hemostatic agents have limitations, necessitating the development of enhanced solutions. In this study, we developed cryogels using agarose and polydopamine microspheres as a hemostatic dressing to effectively manage profuse bleeding. The resulting cryogels demonstrated impressive attributes, such as high absorption capacity (>4000%), shape recovery ability, antioxidant properties, and excellent biocompatibility in mammalian cell lines. Particularly noteworthy was the rapid blood clotting observed in vitro, with the agarose/PDA cryogels achieving complete clotting within just 90 s. Subsequent validation in the rat trauma model further underscored their hemostatic efficacy, with clotting times of 40 and 53 s recorded in tail amputation and liver puncture models, respectively. The porous structure and hydrophilicity of the cryogels facilitated superior blood absorption and retention, while the amine groups of polydopamine played a pivotal role in enhancing blood clotting activity. This study represents a significant step forward in utilizing agarose/polydopamine cryogels as advanced materials for hemostatic wound dressings, promising an impactful contribution to wound therapy.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142337255","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}
Pub Date : 2024-10-21Epub Date: 2024-10-10DOI: 10.1021/acsabm.4c01218
Jie Wang, Yongyuan Kang, Xiaoqing Liu, Bohui Shao, Pai Peng, Wenxing Liu, Changyou Gao
Bacterial infections significantly deteriorate the process of wound healing. The wound dressings loaded with antimicrobials are widely used to reduce bacterial infections. However, release-based sterilization may increase the risk of drug resistance of bacteria and complicate translation. Thus, the development of long-term intrinsic antibacterial wound dressings is highly desirable. In this study, an intrinsic antibacterial hydrogel (PVA/PPG-HBPL) consisting of poly(vinyl alcohol) (PVA), poly(polyethylene glycol methyl ether methacrylate-co-glycidyl methacrylate) (PPG), and hyperbranched poly-l-lysine (HBPL) was designed and fabricated. The mechanical properties of the PVA/PPG-HBPL hydrogel were enhanced by hydrogen bonding and semi-interpenetrating networks. It also possessed a favorable ability to absorb the wound exudates. The release of antibacterial HBPL was significantly decreased by the methods of cyclic freeze-thawing and covalent cross-linking during hydrogel fabrication, enabling the PVA/PPG-HBPL hydrogel with intrinsic and long-term antibacterial performance. The PVA/PPG-HBPL hydrogel dressing killed 99.9% of methicillin-resistant Staphylococcus aureus (MRSA) cultured on its surface without observable cytotoxicity in vitro. It observably shortened the healing process by 2 orders of magnitude of MRSA colonies compared with the control in the MRSA-infected full-thickness skin wound of rats in vivo even after being soaked in phosphate-buffered saline (PBS) for 21 days (PBS was changed every 3 days). The antibacterial hydrogels could kill wound bacteria in a timely manner, significantly reduce inflammatory cell infiltration, and promote neovascularization and collagen deposition.
{"title":"Semi-Interpenetrating Hydrogel with Long-Term Intrinsic Antibacterial Properties Promotes Healing of Infected Wounds <i>In Vivo</i>.","authors":"Jie Wang, Yongyuan Kang, Xiaoqing Liu, Bohui Shao, Pai Peng, Wenxing Liu, Changyou Gao","doi":"10.1021/acsabm.4c01218","DOIUrl":"10.1021/acsabm.4c01218","url":null,"abstract":"<p><p>Bacterial infections significantly deteriorate the process of wound healing. The wound dressings loaded with antimicrobials are widely used to reduce bacterial infections. However, release-based sterilization may increase the risk of drug resistance of bacteria and complicate translation. Thus, the development of long-term intrinsic antibacterial wound dressings is highly desirable. In this study, an intrinsic antibacterial hydrogel (PVA/PPG-HBPL) consisting of poly(vinyl alcohol) (PVA), poly(polyethylene glycol methyl ether methacrylate-<i>co</i>-glycidyl methacrylate) (PPG), and hyperbranched poly-l-lysine (HBPL) was designed and fabricated. The mechanical properties of the PVA/PPG-HBPL hydrogel were enhanced by hydrogen bonding and semi-interpenetrating networks. It also possessed a favorable ability to absorb the wound exudates. The release of antibacterial HBPL was significantly decreased by the methods of cyclic freeze-thawing and covalent cross-linking during hydrogel fabrication, enabling the PVA/PPG-HBPL hydrogel with intrinsic and long-term antibacterial performance. The PVA/PPG-HBPL hydrogel dressing killed 99.9% of methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) cultured on its surface without observable cytotoxicity <i>in vitro</i>. It observably shortened the healing process by 2 orders of magnitude of <i>MRSA</i> colonies compared with the control in the MRSA-infected full-thickness skin wound of rats <i>in vivo</i> even after being soaked in phosphate-buffered saline (PBS) for 21 days (PBS was changed every 3 days). The antibacterial hydrogels could kill wound bacteria in a timely manner, significantly reduce inflammatory cell infiltration, and promote neovascularization and collagen deposition.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142398672","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}
Pub Date : 2024-10-21Epub Date: 2024-09-06DOI: 10.1021/acsabm.4c00854
Sai Kumari Vechalapu, Rakesh Kumar, Sharad Kumar Sachan, Kanchan Shaikh, Amarjyoti Das Mahapatra, Apparao Draksharapu, Dharmaraja Allimuthu
Leveraging the versatile redox behavior of transition metal complexes with heterocyclic ligands offers significant potential for discovering new anticancer therapeutics. This study presents a systematic investigation of a pyridinecarboxaldimine ligand (PyIm) with late 3d-transition metals inhibiting cancer cell proliferation and the mechanism of action. Synthesis and thorough characterization of authentic metal complexes of redox-active late 3d-transition metals enabled the validation of antiproliferative activity in liver cancer cells. Notably, (PyIm)2Mn(II) (1) and (PyIm)2Cu(II) (5) complexes exhibited a good inhibitory profile against liver cancer cells (EC50: 4.0 μM for 1 and 1.7 μM for 5) with excellent selectivity over normal kidney cells (Selectivity index, SI = 17 for 5). Subsequently, evaluation of these complexes in cancers cell lines from four different sites of origin (liver, breast, blood, and bone) demonstrated a predominant selectivity to liver and a moderate selectivity to breast cancer and leukemia cells over the normal kidney cells. The mechanism of action studies highlighted no expected DNA damage in cells, rather, the enhancement of extracellular and intracellular reactive oxygen species (ROS) resulting in mitochondrial damage leading to oxidative cell death in cancer cells. Notably, these complexes potentiated the antiproliferative effect of commercially used cancer therapeutics (cisplatin, oxaliplatin, doxorubicin, and dasatinib) in liver cancer cells. These findings position redox-active metal complexes for further evaluation as promising candidates for developing anticancer therapeutics and combination therapies.
利用过渡金属配合物与杂环配体的多功能氧化还原行为,为发现新的抗癌疗法提供了巨大的潜力。本研究系统研究了吡啶甲酸二甲酰亚胺配体(PyIm)与晚期 3d 过渡金属抑制癌细胞增殖的作用及其机制。通过对具有氧化还原作用的晚 3d 过渡金属的真实金属复合物进行合成和全面表征,验证了其在肝癌细胞中的抗增殖活性。值得注意的是,(PyIm)2Mn(II) (1) 和 (PyIm)2Cu(II) (5) 复合物对肝癌细胞具有良好的抑制作用(EC50:1 为 4.0 μM,5 为 1.7 μM),对正常肾细胞具有极佳的选择性(5 的选择性指数 SI = 17)。随后,在来自四个不同来源部位(肝脏、乳腺、血液和骨骼)的癌症细胞系中对这些复合物进行了评估,结果表明,与正常肾脏细胞相比,这些复合物对肝脏细胞具有主要选择性,对乳腺癌和白血病细胞具有中等选择性。作用机理研究表明,细胞中不会出现预期的 DNA 损伤,相反,细胞外和细胞内活性氧(ROS)的增强会导致线粒体损伤,从而导致癌细胞氧化死亡。值得注意的是,这些复合物增强了市售癌症治疗药物(顺铂、奥沙利铂、多柔比星和达沙替尼)对肝癌细胞的抗增殖作用。这些发现将氧化还原活性金属复合物定位为开发抗癌疗法和联合疗法的理想候选物质,并对其进行进一步评估。
{"title":"Copper and Manganese Complexes of Pyridinecarboxaldimine Induce Oxidative Cell Death in Cancer Cells.","authors":"Sai Kumari Vechalapu, Rakesh Kumar, Sharad Kumar Sachan, Kanchan Shaikh, Amarjyoti Das Mahapatra, Apparao Draksharapu, Dharmaraja Allimuthu","doi":"10.1021/acsabm.4c00854","DOIUrl":"10.1021/acsabm.4c00854","url":null,"abstract":"<p><p>Leveraging the versatile redox behavior of transition metal complexes with heterocyclic ligands offers significant potential for discovering new anticancer therapeutics. This study presents a systematic investigation of a pyridinecarboxaldimine ligand (PyIm) with late 3d-transition metals inhibiting cancer cell proliferation and the mechanism of action. Synthesis and thorough characterization of authentic metal complexes of redox-active late 3d-transition metals enabled the validation of antiproliferative activity in liver cancer cells. Notably, (PyIm)<sub>2</sub>Mn(II) (<b>1</b>) and (PyIm)<sub>2</sub>Cu(II) (<b>5</b>) complexes exhibited a good inhibitory profile against liver cancer cells (EC<sub>50</sub>: 4.0 μM for <b>1</b> and 1.7 μM for <b>5</b>) with excellent selectivity over normal kidney cells (Selectivity index, SI = 17 for <b>5</b>). Subsequently, evaluation of these complexes in cancers cell lines from four different sites of origin (liver, breast, blood, and bone) demonstrated a predominant selectivity to liver and a moderate selectivity to breast cancer and leukemia cells over the normal kidney cells. The mechanism of action studies highlighted no expected DNA damage in cells, rather, the enhancement of extracellular and intracellular reactive oxygen species (ROS) resulting in mitochondrial damage leading to oxidative cell death in cancer cells. Notably, these complexes potentiated the antiproliferative effect of commercially used cancer therapeutics (cisplatin, oxaliplatin, doxorubicin, and dasatinib) in liver cancer cells. These findings position redox-active metal complexes for further evaluation as promising candidates for developing anticancer therapeutics and combination therapies.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142143006","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}
Reuniting denuded nerve ends after a long segmental peripheral nerve defect is challenging due to delayed axonal regeneration and incomplete, nonspecific reinnervation, as conventional hollow nerve guides fail to ensure proper fascicular complementation and obstruct axonal guidance across the defects. This study focuses on fabricating multifilament conduits using a plant-derived anionic polysaccharide, pectin, where the abundant availability of carboxylate (COO-) functional groups in pectin facilitates instantaneous sol-gel transition upon interaction with divalent cations. Despite their advantages, pectin hydrogels encounter structural instability under physiological conditions. Hence, pectin is conjugated with light-sensitive methacrylate residues (49.8% methacrylation) to overcome these issues, enabling the fabrication of dual cross-linked multifilament nerve conduits through an ionic interaction-driven, template-free 3D wet writing process, followed by photo-cross-linking at 525 nm. The anatomical equivalence including peri-, epi-, and endoneurium structures of the customized multifilament conduits was confirmed through scanning electron micrographs and micro-CT analysis of rat and goat sciatic nerve tissues. Furthermore, the fabricated multifilament nerve conduits demonstrated cytocompatibility and promoted the expression of neuron-specific intermediate filament protein (NF-200) in PC12 cells and neurite outgrowth of 16.90 ± 1.82 μm on day 14. Micro-CT imaging of an anastomosed native goat sciatic nerve with an 8-filament conduit demonstrated precise fascicular complementation in an ex vivo interpositional goat model. This approach not only eliminates the need for a suture-intensive ligation process but also highlights the customizability of multifilament conduits to meet patient- and injury-specific needs.
{"title":"Fabrication of Anatomically Equivalent Pectin-Based Multifilament Nerve Conduits.","authors":"Preethy Amruthavarshini Ramesh, Swaminathan Sethuraman, Anuradha Subramanian","doi":"10.1021/acsabm.4c00872","DOIUrl":"10.1021/acsabm.4c00872","url":null,"abstract":"<p><p>Reuniting denuded nerve ends after a long segmental peripheral nerve defect is challenging due to delayed axonal regeneration and incomplete, nonspecific reinnervation, as conventional hollow nerve guides fail to ensure proper fascicular complementation and obstruct axonal guidance across the defects. This study focuses on fabricating multifilament conduits using a plant-derived anionic polysaccharide, pectin, where the abundant availability of carboxylate (COO-) functional groups in pectin facilitates instantaneous sol-gel transition upon interaction with divalent cations. Despite their advantages, pectin hydrogels encounter structural instability under physiological conditions. Hence, pectin is conjugated with light-sensitive methacrylate residues (49.8% methacrylation) to overcome these issues, enabling the fabrication of dual cross-linked multifilament nerve conduits through an ionic interaction-driven, template-free 3D wet writing process, followed by photo-cross-linking at 525 nm. The anatomical equivalence including peri-, epi-, and endoneurium structures of the customized multifilament conduits was confirmed through scanning electron micrographs and micro-CT analysis of rat and goat sciatic nerve tissues. Furthermore, the fabricated multifilament nerve conduits demonstrated cytocompatibility and promoted the expression of neuron-specific intermediate filament protein (NF-200) in PC12 cells and neurite outgrowth of 16.90 ± 1.82 μm on day 14. Micro-CT imaging of an anastomosed native goat sciatic nerve with an 8-filament conduit demonstrated precise fascicular complementation in an ex vivo interpositional goat model. This approach not only eliminates the need for a suture-intensive ligation process but also highlights the customizability of multifilament conduits to meet patient- and injury-specific needs.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142330467","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}
Pub Date : 2024-10-21Epub Date: 2024-10-04DOI: 10.1021/acsabm.4c00559
Francisco José Calero-Castro, Víctor Manuel Perez-Puyana, Imán Laga, Javier Padillo Ruiz, Alberto Romero, Fernando de la Portilla de Juan
The current treatments to restore skeletal muscle defects present several injuries. The creation of scaffolds and implant that allow the regeneration of this tissue is a solution that is reaching the researchers' interest. To achieve this, electrospinning is a useful technique to manufacture scaffolds with nanofibers with different orientation. In this work, polycaprolactone and gelatin solutions were tested to fabricate electrospun scaffolds with two degrees of alignment between their fibers: random and aligned. These scaffolds can be seeded with myoblast C2C12 and then stimulated with a mechanical bioreactor that mimics the physiological conditions of the tissue. Cell viability as well as cytoskeletal morphology and functionality was measured. Myotubes in aligned scaffolds (9.84 ± 1.15 μm) were thinner than in random scaffolds (11.55 ± 3.39 μm; P = 0.001). Mechanical stimulation increased the width of myotubes (12.92 ± 3.29 μm; P < 0.001), nuclear fusion (95.73 ± 1.05%; P = 0.004), and actin density (80.13 ± 13.52%; P = 0.017) in aligned scaffolds regarding the control. Moreover, both scaffolds showed high myotube contractility, which was increased in mechanically stimulated aligned scaffolds. These scaffolds were also electrostimulated at different frequencies and they showed promising results. In general, mechanically stimulated aligned scaffolds allow the regeneration of skeletal muscle, increasing viability, fiber thickness, alignment, nuclear fusion, nuclear differentiation, and functionality.
{"title":"Mechanical Stimulation and Aligned Poly(ε-caprolactone)-Gelatin Electrospun Scaffolds Promote Skeletal Muscle Regeneration.","authors":"Francisco José Calero-Castro, Víctor Manuel Perez-Puyana, Imán Laga, Javier Padillo Ruiz, Alberto Romero, Fernando de la Portilla de Juan","doi":"10.1021/acsabm.4c00559","DOIUrl":"10.1021/acsabm.4c00559","url":null,"abstract":"<p><p>The current treatments to restore skeletal muscle defects present several injuries. The creation of scaffolds and implant that allow the regeneration of this tissue is a solution that is reaching the researchers' interest. To achieve this, electrospinning is a useful technique to manufacture scaffolds with nanofibers with different orientation. In this work, polycaprolactone and gelatin solutions were tested to fabricate electrospun scaffolds with two degrees of alignment between their fibers: random and aligned. These scaffolds can be seeded with myoblast C2C12 and then stimulated with a mechanical bioreactor that mimics the physiological conditions of the tissue. Cell viability as well as cytoskeletal morphology and functionality was measured. Myotubes in aligned scaffolds (9.84 ± 1.15 μm) were thinner than in random scaffolds (11.55 ± 3.39 μm; <i>P</i> = 0.001). Mechanical stimulation increased the width of myotubes (12.92 ± 3.29 μm; <i>P</i> < 0.001), nuclear fusion (95.73 ± 1.05%; <i>P</i> = 0.004), and actin density (80.13 ± 13.52%; <i>P</i> = 0.017) in aligned scaffolds regarding the control. Moreover, both scaffolds showed high myotube contractility, which was increased in mechanically stimulated aligned scaffolds. These scaffolds were also electrostimulated at different frequencies and they showed promising results. In general, mechanically stimulated aligned scaffolds allow the regeneration of skeletal muscle, increasing viability, fiber thickness, alignment, nuclear fusion, nuclear differentiation, and functionality.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142374736","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}
Pub Date : 2024-10-21Epub Date: 2024-10-09DOI: 10.1021/acsabm.4c00586
Ashoka Karunarathne, Günel Nabiyeva, Christopher J Rasmussen, Keven Alkhoury, Naila Assem, Jonathan Bauer, Shawn A Chester, Alexei F Khalizov, Gennady Y Gor
Leather is a product that has been used for millennia. While it is a natural material, its production raises serious environmental and ethical concerns. To mitigate those, the engineering of sustainable biobased leather substitutes has become a trend over the past few years. Among the biobased materials, mycelium, the fungal "root" of a mushroom, is one of the promising alternatives to animal leather, as a material with tunable physicomechanical properties. Understanding the effect of humidity on mycelium-based leather material properties is essential to the production of durable, competitive, and sustainable leather products. To this end, we measured the water sorption isotherms on several samples of mycelium-based leather materials and investigated the effects of water sorption on their elastic properties. The ultrasonic pulse transmission method was used to measure the wave speed through the materials while measuring their sorption isotherms at different humidity levels. Additionally, the material's properties were mechanically tested by performing uniaxial tensile tests under ambient and immersed conditions. An overall reduction in elastic moduli was observed during both absorption and immersion. The changes in the measured longitudinal modulus during water sorption reveal changes in the elasticity of the test materials. The observed irreversible variation of the longitudinal modulus during the initial water sorption can be related to the material production process and the presence of various additives that affect the mechanical properties of the leather materials. Our results presented here should be of interest to material science experts developing a new generation of sustainable leather products.
{"title":"Effects of Humidity on Mycelium-Based Leather.","authors":"Ashoka Karunarathne, Günel Nabiyeva, Christopher J Rasmussen, Keven Alkhoury, Naila Assem, Jonathan Bauer, Shawn A Chester, Alexei F Khalizov, Gennady Y Gor","doi":"10.1021/acsabm.4c00586","DOIUrl":"10.1021/acsabm.4c00586","url":null,"abstract":"<p><p>Leather is a product that has been used for millennia. While it is a natural material, its production raises serious environmental and ethical concerns. To mitigate those, the engineering of sustainable biobased leather substitutes has become a trend over the past few years. Among the biobased materials, mycelium, the fungal \"root\" of a mushroom, is one of the promising alternatives to animal leather, as a material with tunable physicomechanical properties. Understanding the effect of humidity on mycelium-based leather material properties is essential to the production of durable, competitive, and sustainable leather products. To this end, we measured the water sorption isotherms on several samples of mycelium-based leather materials and investigated the effects of water sorption on their elastic properties. The ultrasonic pulse transmission method was used to measure the wave speed through the materials while measuring their sorption isotherms at different humidity levels. Additionally, the material's properties were mechanically tested by performing uniaxial tensile tests under ambient and immersed conditions. An overall reduction in elastic moduli was observed during both absorption and immersion. The changes in the measured longitudinal modulus during water sorption reveal changes in the elasticity of the test materials. The observed irreversible variation of the longitudinal modulus during the initial water sorption can be related to the material production process and the presence of various additives that affect the mechanical properties of the leather materials. Our results presented here should be of interest to material science experts developing a new generation of sustainable leather products.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142386335","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}
Pub Date : 2024-10-21Epub Date: 2024-10-07DOI: 10.1021/acsabm.4c00988
Khaled AbouAitah, Ramadan A Geioushy, Shaimaa A Nour, Maha T H Emam, Mohammed A Zakaria, Osama A Fouad, Yasser M Shaker, Beom Soo Kim
Microbial combating is one of the hot research topics, and finding an alternative strategy is considerably required nowadays. Here, we report on a developed combined chemo- and photodynamic delivery system with a core of zinc oxide nanoparticles (ZnO NPs), porphyrin photosensitizer (POR) connected to alginate polymer (ALG), and berberine (alkaloid natural agent, BER) with favorable antimicrobial effects. According to the achieved main designs, the results demonstrated that the loading capacity and entrapment efficiency reached 22.2 wt % and 95.2%, respectively, for ZnO@ALG-POR/BER nanoformulation (second design) compared to 5.88 wt % and 45.1% for ZnOBER@ALG-POR design (first design). Importantly, when the intended nanoformulations were combined with laser irradiation for 10 min, they showed effective antifungal and antibacterial action against Candida albicans, Escherichia coli, and Staphylococcus aureus. Comparing these treatments to ZnO NPs and free BER, a complete (100%) suppression of bacterial and fungal growth was observed by ZnO@ALG-POR/BER nanoformulation treated E. coli, and by ZnOBER treated C. albicans. Also, after laser treatments, most data showed that E. coli was more sensitive to treatments using nanoformulations than S. aureus. The nanoformulations like ZnOBER@ALG-POR were highly comparable to traditional antibiotics against C. albicans and E. coli before laser application. The results of the cytotoxicity assessment demonstrated that the nanoformulations exhibited moderate biocompatibility on normal human immortalized retinal epithelial (RPE1) cells. Notably, the most biocompatible nanoformulation was ZnOBER@ALG-POR, which possessed ∼9% inhibition of RPE1 cells compared to others. High binding affinities were found between all three microbial strains' receptor proteins and ligands in the molecular docking interaction between the receptor proteins and the ligand molecules (mostly BER and POR). In conclusion, our findings point to the possible use of hybrid nanoplatform delivery systems that combine natural agents and photodynamic therapy into a single therapeutic agent, effectively combating microbial infections. Therapeutic efficiency correlates with nanoformulation design and microorganisms, demonstrating possible optimization for further development.
{"title":"A Combined Phyto- and Photodynamic Delivery Nanoplatform Enhances Antimicrobial Therapy: Design, Preparation, In Vitro Evaluation, and Molecular Docking.","authors":"Khaled AbouAitah, Ramadan A Geioushy, Shaimaa A Nour, Maha T H Emam, Mohammed A Zakaria, Osama A Fouad, Yasser M Shaker, Beom Soo Kim","doi":"10.1021/acsabm.4c00988","DOIUrl":"10.1021/acsabm.4c00988","url":null,"abstract":"<p><p>Microbial combating is one of the hot research topics, and finding an alternative strategy is considerably required nowadays. Here, we report on a developed combined chemo- and photodynamic delivery system with a core of zinc oxide nanoparticles (ZnO NPs), porphyrin photosensitizer (POR) connected to alginate polymer (ALG), and berberine (alkaloid natural agent, BER) with favorable antimicrobial effects. According to the achieved main designs, the results demonstrated that the loading capacity and entrapment efficiency reached 22.2 wt % and 95.2%, respectively, for ZnO@ALG-POR/BER nanoformulation (second design) compared to 5.88 wt % and 45.1% for ZnOBER@ALG-POR design (first design). Importantly, when the intended nanoformulations were combined with laser irradiation for 10 min, they showed effective antifungal and antibacterial action against <i>Candida albicans</i>, <i>Escherichia coli</i>, and <i>Staphylococcus aureus</i>. Comparing these treatments to ZnO NPs and free BER, a complete (100%) suppression of bacterial and fungal growth was observed by ZnO@ALG-POR/BER nanoformulation treated <i>E. coli</i>, and by ZnOBER treated <i>C. albicans</i>. Also, after laser treatments, most data showed that <i>E. coli</i> was more sensitive to treatments using nanoformulations than <i>S. aureus</i>. The nanoformulations like ZnOBER@ALG-POR were highly comparable to traditional antibiotics against <i>C. albicans</i> and <i>E. coli</i> before laser application. The results of the cytotoxicity assessment demonstrated that the nanoformulations exhibited moderate biocompatibility on normal human immortalized retinal epithelial (RPE1) cells. Notably, the most biocompatible nanoformulation was ZnOBER@ALG-POR, which possessed ∼9% inhibition of RPE1 cells compared to others. High binding affinities were found between all three microbial strains' receptor proteins and ligands in the molecular docking interaction between the receptor proteins and the ligand molecules (mostly BER and POR). In conclusion, our findings point to the possible use of hybrid nanoplatform delivery systems that combine natural agents and photodynamic therapy into a single therapeutic agent, effectively combating microbial infections. Therapeutic efficiency correlates with nanoformulation design and microorganisms, demonstrating possible optimization for further development.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142386369","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}
Expanded polytetrafluoroethylene (ePTFE) failed to achieve clinical application in the field of small-diameter blood vessels due to its lack of elasticity in the circumferential direction and high stiffness. Excellent multidirectional elasticity and dynamic compliance matching with natural blood vessels are important means to solve the problem of acute thrombosis and poor long-term patency. Herein, novel PTFE spinning blood vessels were prepared by the PTFE emulsion electrospinning process, which not only presented good bidirectional elasticity but also promoted the adhesion and proliferation of endothelial cells and induced the contractile expression of SMCs. And, a PTFE-shish and aminated polycaprolactone (PCL)-kebab structure has been developed that converted the chemically inert PTFE surface into a drug-loading platform for the multifunctionalization of PTFE vascular grafts. It provides novel preparation methods for the application of new bidirectional elastic small-diameter artificial blood vessels and their surface functionalization construction.
{"title":"Bidirectional Elastic PTFE Small Diameter Artificial Blood Vessel Grafts and Surface Antithrombotic Functionalized Construction.","authors":"Siqi Zhou, Yulu Liu, Xueke Yu, Dongfang Wang, Xiaofeng Wang, Qian Li","doi":"10.1021/acsabm.4c01098","DOIUrl":"10.1021/acsabm.4c01098","url":null,"abstract":"<p><p>Expanded polytetrafluoroethylene (ePTFE) failed to achieve clinical application in the field of small-diameter blood vessels due to its lack of elasticity in the circumferential direction and high stiffness. Excellent multidirectional elasticity and dynamic compliance matching with natural blood vessels are important means to solve the problem of acute thrombosis and poor long-term patency. Herein, novel PTFE spinning blood vessels were prepared by the PTFE emulsion electrospinning process, which not only presented good bidirectional elasticity but also promoted the adhesion and proliferation of endothelial cells and induced the contractile expression of SMCs. And, a PTFE-shish and aminated polycaprolactone (PCL)-kebab structure has been developed that converted the chemically inert PTFE surface into a drug-loading platform for the multifunctionalization of PTFE vascular grafts. It provides novel preparation methods for the application of new bidirectional elastic small-diameter artificial blood vessels and their surface functionalization construction.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142386368","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}
In this study, we synthesized polyelectrolyte complexed nanoparticles using an ion exchange reaction between poly(hexamethylene guanidine hydrochloride) and sodium caffeate. The morphology of the obtained antiparticle was observed by scanning electron microscopy, and FT-IR and XPS were employed for the structural characterization. The antimicrobial properties of E. coli and S. aureus were characterized through minimum inhibitory concentration (MIC), growth curve analysis, plate colony counting method, and crystal violet method. Notably, the sample showed a 100% bactericidal rate against E. coli at 0.095 μg/mL and against S. aureus at 0.375 μg/mL within 1 h, demonstrating excellent antimicrobial performance against E. coli and S. aureus. The CA-PHMG-containing acrylic resin coatings exhibited exceptional antimicrobial and antiadhesive properties when examined under an inverted fluorescence microscope, particularly at a 4% weight concentration of the antibacterial agent. This study holds vast potential for development in the field of antimicrobial coatings.
{"title":"Preparation and Antibacterial Properties of Polyelectrolyte Complexed Nanoparticles Aggregated from PHMG and Sodium Caffeate.","authors":"Mingyuan Tang, Xiaoxian Hao, Yuanyuan Kang, Xiaofeng He, Haichao Zhao","doi":"10.1021/acsabm.4c00584","DOIUrl":"10.1021/acsabm.4c00584","url":null,"abstract":"<p><p>In this study, we synthesized polyelectrolyte complexed nanoparticles using an ion exchange reaction between poly(hexamethylene guanidine hydrochloride) and sodium caffeate. The morphology of the obtained antiparticle was observed by scanning electron microscopy, and FT-IR and XPS were employed for the structural characterization. The antimicrobial properties of <i>E. coli</i> and <i>S. aureus</i> were characterized through minimum inhibitory concentration (MIC), growth curve analysis, plate colony counting method, and crystal violet method. Notably, the sample showed a 100% bactericidal rate against <i>E. coli</i> at 0.095 μg/mL and against <i>S. aureus</i> at 0.375 μg/mL within 1 h, demonstrating excellent antimicrobial performance against <i>E. coli</i> and <i>S. aureus.</i> The CA-PHMG-containing acrylic resin coatings exhibited exceptional antimicrobial and antiadhesive properties when examined under an inverted fluorescence microscope, particularly at a 4% weight concentration of the antibacterial agent. This study holds vast potential for development in the field of antimicrobial coatings.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142138552","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}