Photodynamic therapy (PDT) using aggregation-induced emission photosensitizer (AIE-PS) holds tremendous potential but is limited by its inherent disadvantages and the high concentrations of reduced glutathione (GSH) in tumor cells that can neutralize ROS to weaken PDT. Herein, we designed a nanodelivery system (CM-HSADSP@[PS-Sor]) in which albumin was utilized as a carrier for hydrophobic drug AIE-PS and Sorafenib, cross-linkers with disulfide bonds were introduced to form a nanogel core, and then cancer cell membranes were wrapped on its surface to confer homologous tumor targeting ability. A two-way strategy was employed to disturb redox-homeostasis through blocking GSH synthesis by Sorafenib and consuming excess GSH via abundant disulfide bonds, thereby promoting the depletion of GSH, which in turn increased the ROS levels in cancer cells to amplify the efficacy of ferroptosis and PDT, achieving an efficient in vivo antibreast cancer effect. This study brings a new strategy for ROS-based cancer therapy and expands the application of an albumin-based drug delivery system.
{"title":"Biomimetic Cancer-Targeting Nanoplatform Boosting AIEgens-Based Photodynamic Therapy and Ferroptosis by Disrupting Redox-Homeostasis","authors":"Yu Wan*, Yifei Cao, Dandan Hu, Qiuyue Lai, Yumeng Liu, Yuan Chen, Mingyu Wu* and Shun Feng*, ","doi":"10.1021/acsbiomaterials.4c00376","DOIUrl":"10.1021/acsbiomaterials.4c00376","url":null,"abstract":"<p >Photodynamic therapy (PDT) using aggregation-induced emission photosensitizer (AIE-PS) holds tremendous potential but is limited by its inherent disadvantages and the high concentrations of reduced glutathione (GSH) in tumor cells that can neutralize ROS to weaken PDT. Herein, we designed a nanodelivery system (CM-HSA<sup>DSP</sup>@[PS-Sor]) in which albumin was utilized as a carrier for hydrophobic drug AIE-PS and Sorafenib, cross-linkers with disulfide bonds were introduced to form a nanogel core, and then cancer cell membranes were wrapped on its surface to confer homologous tumor targeting ability. A two-way strategy was employed to disturb redox-homeostasis through blocking GSH synthesis by Sorafenib and consuming excess GSH via abundant disulfide bonds, thereby promoting the depletion of GSH, which in turn increased the ROS levels in cancer cells to amplify the efficacy of ferroptosis and PDT, achieving an efficient in vivo antibreast cancer effect. This study brings a new strategy for ROS-based cancer therapy and expands the application of an albumin-based drug delivery system.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141079804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-23DOI: 10.1021/acsbiomaterials.4c00040
Euisun Song, Jae Won Kwon, Choul Yong Park, Jung-Taek Kang and Kwideok Park*,
Human corneal transplantation is still the only option to restore the function of corneal endothelial cells (CECs). Therefore, there is an urgent need for hCEC delivery systems to replace the human donor cornea. Here, we propose an alginate hydrogel (AH)-based delivery system, where a human fibroblast-derived, decellularized extracellular matrix (ECM) was physically integrated with AH. This AH securely combined with the ECM (ECM-AH) was approximately 50 μm thick, transparent, and permeable. The surface roughness and surface potential provided ECM-AH with a favorable microenvironment for CEC adhesion and growth in vitro. More importantly, ECM-AH could support the structural (ZO-1) and functional (Na+/K+-ATPase) markers of hCECs, as assessed via western blotting and quantitative polymerase chain reaction, which were comparable with those of a ferritic nitrocarburizing (FNC)-coated substrate (a positive control). The cell density per unit area was also significantly better with ECM-AH than the FNC substrate at day 7. A simulation test of cell engraftment in vitro showed that hCECs were successfully transferred into the decellularized porcine corneal tissue, where they were mostly alive. Furthermore, we found out that the endothelial–mesenchymal transition (EnMT)-inductive factors (Smad2 and vimentin) were largely declined with the hCECs grown on ECM-AH, whereas the EnMT inhibitory factor (Smad7) was significantly elevated. The difference was statistically significant compared to that of the FNC substrate. Moreover, we also observed that TGF-β1-treated hCECs showed faster recovery of cell phenotype on the ECM. Taken together, our study demonstrates that ECM-AH is a very promising material for hCEC culture and delivery, which endows an excellent microenvironment for cell function and phenotype maintenance.
{"title":"Alginate Hydrogel Integrated with a Human Fibroblast-Derived Extracellular Matrix Supports Corneal Endothelial Cell Functionality and Suppresses Endothelial–Mesenchymal Transition","authors":"Euisun Song, Jae Won Kwon, Choul Yong Park, Jung-Taek Kang and Kwideok Park*, ","doi":"10.1021/acsbiomaterials.4c00040","DOIUrl":"10.1021/acsbiomaterials.4c00040","url":null,"abstract":"<p >Human corneal transplantation is still the only option to restore the function of corneal endothelial cells (CECs). Therefore, there is an urgent need for hCEC delivery systems to replace the human donor cornea. Here, we propose an alginate hydrogel (AH)-based delivery system, where a human fibroblast-derived, decellularized extracellular matrix (ECM) was physically integrated with AH. This AH securely combined with the ECM (ECM-AH) was approximately 50 μm thick, transparent, and permeable. The surface roughness and surface potential provided ECM-AH with a favorable microenvironment for CEC adhesion and growth in vitro. More importantly, ECM-AH could support the structural (ZO-1) and functional (Na<sup>+</sup>/K<sup>+</sup>-ATPase) markers of hCECs, as assessed via western blotting and quantitative polymerase chain reaction, which were comparable with those of a ferritic nitrocarburizing (FNC)-coated substrate (a positive control). The cell density per unit area was also significantly better with ECM-AH than the FNC substrate at day 7. A simulation test of cell engraftment in vitro showed that hCECs were successfully transferred into the decellularized porcine corneal tissue, where they were mostly alive. Furthermore, we found out that the endothelial–mesenchymal transition (EnMT)-inductive factors (Smad2 and vimentin) were largely declined with the hCECs grown on ECM-AH, whereas the EnMT inhibitory factor (Smad7) was significantly elevated. The difference was statistically significant compared to that of the FNC substrate. Moreover, we also observed that TGF-β1-treated hCECs showed faster recovery of cell phenotype on the ECM. Taken together, our study demonstrates that ECM-AH is a very promising material for hCEC culture and delivery, which endows an excellent microenvironment for cell function and phenotype maintenance.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141079780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-22DOI: 10.1021/acsbiomaterials.4c00259
Chen Guo, Xinbang Jiang, Xiaofang Guo and Lailiang Ou*,
Accumulation of pathogenic factors in the blood may cause irreversible damage and may even be life-threatening. Hemoperfusion is an effective technique for eliminating pathogenic factors, which is widely used in the treatment of various diseases including liver failure, renal failure, sepsis, and others. Hemoperfusion adsorbents are crucial in this process as they specifically bind and remove the target pathogenic factors. This review describes the development of hemoperfusion adsorbents, detailing the different properties exhibited by inorganic materials, organic polymers, and new materials. Advances in natural and synthetic polymers and novel materials manufacturing techniques have driven the expansion of hemoperfusion adsorbents in clinical applications. Stimuli-responsive (smart responsive) adsorbents with controllable molecular binding properties have many promising and environmentally friendly biomedical applications. Knowledge gaps, future research directions, and prospects for hemoperfusion adsorbents are discussed.
{"title":"An Evolutionary Review of Hemoperfusion Adsorbents: Materials, Preparation, Functionalization, and Outlook","authors":"Chen Guo, Xinbang Jiang, Xiaofang Guo and Lailiang Ou*, ","doi":"10.1021/acsbiomaterials.4c00259","DOIUrl":"10.1021/acsbiomaterials.4c00259","url":null,"abstract":"<p >Accumulation of pathogenic factors in the blood may cause irreversible damage and may even be life-threatening. Hemoperfusion is an effective technique for eliminating pathogenic factors, which is widely used in the treatment of various diseases including liver failure, renal failure, sepsis, and others. Hemoperfusion adsorbents are crucial in this process as they specifically bind and remove the target pathogenic factors. This review describes the development of hemoperfusion adsorbents, detailing the different properties exhibited by inorganic materials, organic polymers, and new materials. Advances in natural and synthetic polymers and novel materials manufacturing techniques have driven the expansion of hemoperfusion adsorbents in clinical applications. Stimuli-responsive (smart responsive) adsorbents with controllable molecular binding properties have many promising and environmentally friendly biomedical applications. Knowledge gaps, future research directions, and prospects for hemoperfusion adsorbents are discussed.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141079781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-22DOI: 10.1021/acsbiomaterials.4c00546
Xiaojie Cao, Xiaoyan Li, Min Li, Jiawei Sun, Zhaoshuai Gao, Xiaowei Li, Qian Li, Zhifeng Shao, Chunhai Fan, Jielin Sun
Visualizing the whole vascular network system is crucial for understanding the pathogenesis of specific diseases and devising targeted therapeutic interventions. Although the combination of light sheet microscopy and tissue-clearing methods has emerged as a promising approach for investigating the blood vascular network, leveraging the spatial resolution down to the capillary level and the ability to image centimeter-scale samples remains difficult. Especially, as the resolution improves, the issue of photobleaching outside the field of view poses a challenge to image the whole vascular network of adult mice at capillary resolution. Here, we devise a fluorescent microsphere vascular perfusion method to enable labeling of the whole vascular network in adult mice, which overcomes the photobleaching limit during the imaging of large samples. Moreover, by combining the utilization of a large-scale light-sheet microscope and tissue clearing protocols for whole-mouse samples, we achieve the capillary-level imaging resolution (3.2 × 3.2 × 6.5 μm) of the whole vascular network with dimensions of 45 × 15 × 82 mm in adult mice. This method thus holds great potential to deliver mesoscopic resolution images of various tissue organs for whole-animal imaging.
{"title":"Light-Sheet Microscopic Imaging of Whole-Mouse Vascular Network with Fluorescent Microsphere Perfusion.","authors":"Xiaojie Cao, Xiaoyan Li, Min Li, Jiawei Sun, Zhaoshuai Gao, Xiaowei Li, Qian Li, Zhifeng Shao, Chunhai Fan, Jielin Sun","doi":"10.1021/acsbiomaterials.4c00546","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.4c00546","url":null,"abstract":"<p><p>Visualizing the whole vascular network system is crucial for understanding the pathogenesis of specific diseases and devising targeted therapeutic interventions. Although the combination of light sheet microscopy and tissue-clearing methods has emerged as a promising approach for investigating the blood vascular network, leveraging the spatial resolution down to the capillary level and the ability to image centimeter-scale samples remains difficult. Especially, as the resolution improves, the issue of photobleaching outside the field of view poses a challenge to image the whole vascular network of adult mice at capillary resolution. Here, we devise a fluorescent microsphere vascular perfusion method to enable labeling of the whole vascular network in adult mice, which overcomes the photobleaching limit during the imaging of large samples. Moreover, by combining the utilization of a large-scale light-sheet microscope and tissue clearing protocols for whole-mouse samples, we achieve the capillary-level imaging resolution (3.2 × 3.2 × 6.5 μm) of the whole vascular network with dimensions of 45 × 15 × 82 mm in adult mice. This method thus holds great potential to deliver mesoscopic resolution images of various tissue organs for whole-animal imaging.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141074747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Building 3D electrospun macrostructures and monitoring the biological activities inside them are challenging. In this study, 3D fibrous polycaprolactone (PCL) macrostructures were successfully fabricated using in-house 3D electrospinning. The main factors supporting the 3D self-assembled nanofiber fabrication are the H3PO4 additives, flow rate, and initial distance. The effects of solution concentration, solvent, H3PO4 concentration, flow rate, initial distance, voltage, and nozzle speed on the 3D macrostructures were examined. The optimal conditions of 4 mL/h flow rate, 4 cm initial nozzle-collector distance, 14 kV voltage, and 1 mm/s nozzle speed provided a rapid buildup of cylinder macrostructures with 6 cm of diameter, reaching a final height of 16.18 ± 2.58 mm and a wall thickness of 3.98 ± 1.01 mm on one perimeter with uniform diameter across different sections (1.40 ± 1.10 μm average). Oxygen plasma treatment with 30-50 W for 5 min significantly improved the hydrophilicity of the PCL macrostructures, proving a suitable scaffold for in vitro cell cultures. Additionally, 3D images obtained by synchrotron radiation X-ray tomographic microscopy (SRXTM) presented cell penetration and cell growth within the scaffolds. This breakthrough in 3D electrospinning surpasses current scaffold fabrication limitations, opening new possibilities in various fields.
{"title":"Fabrication of 3D Polycaprolactone Macrostructures by 3D Electrospinning.","authors":"Atchara Chinnakorn, Yanawarut Soi-Ngoen, Oratai Weeranantanapan, Phakkhananan Pakawanit, Santi Maensiri, Kriettisak Srisom, Pattanaphong Janphuang, Norbert Radacsi, Wiwat Nuansing","doi":"10.1021/acsbiomaterials.4c00302","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.4c00302","url":null,"abstract":"<p><p>Building 3D electrospun macrostructures and monitoring the biological activities inside them are challenging. In this study, 3D fibrous polycaprolactone (PCL) macrostructures were successfully fabricated using in-house 3D electrospinning. The main factors supporting the 3D self-assembled nanofiber fabrication are the H<sub>3</sub>PO<sub>4</sub> additives, flow rate, and initial distance. The effects of solution concentration, solvent, H<sub>3</sub>PO<sub>4</sub> concentration, flow rate, initial distance, voltage, and nozzle speed on the 3D macrostructures were examined. The optimal conditions of 4 mL/h flow rate, 4 cm initial nozzle-collector distance, 14 kV voltage, and 1 mm/s nozzle speed provided a rapid buildup of cylinder macrostructures with 6 cm of diameter, reaching a final height of 16.18 ± 2.58 mm and a wall thickness of 3.98 ± 1.01 mm on one perimeter with uniform diameter across different sections (1.40 ± 1.10 μm average). Oxygen plasma treatment with 30-50 W for 5 min significantly improved the hydrophilicity of the PCL macrostructures, proving a suitable scaffold for in vitro cell cultures. Additionally, 3D images obtained by synchrotron radiation X-ray tomographic microscopy (SRXTM) presented cell penetration and cell growth within the scaffolds. This breakthrough in 3D electrospinning surpasses current scaffold fabrication limitations, opening new possibilities in various fields.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141079806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-20DOI: 10.1021/acsbiomaterials.4c00228
Huanhuan Qiu, Huacui Xiong, Jiafu Zheng, Yuqi Peng, Chunhui Wang, Qing Hu, Fujian Zhao* and Ke Chen*,
The repair of critical-sized bone defects continues to pose a challenge in clinics. Strontium (Sr), recognized for its function in bone metabolism regulation, has shown potential in bone repair. However, the underlying mechanism through which Sr2+ guided favorable osteogenesis by modulating macrophages remains unclear, limiting their application in the design of bone biomaterials. Herein, Sr-incorporated bioactive glass (SrBG) was synthesized for further investigation. The release of Sr ions enhanced the immunomodulatory properties and osteogenic potential by modulating the polarization of macrophages toward the M2 phenotype. In vivo, a 3D-printed SrBG scaffold was fabricated and showed consistently improved bone regeneration by creating a prohealing immunological microenvironment. RNA sequencing was performed to explore the underlying mechanisms. It was found that Sr ions might enhance the mitochondrial function of macrophage by activating PI3K/AKT/mTOR signaling, thereby favoring osteogenesis. Our findings demonstrate the relationship between the immunomodulatory role of Sr ions and the mitochondrial function of macrophages. By focusing on the mitochondrial function of macrophages, Sr2+-mediated immunomodulation sheds light on the future design of biomaterials for tissue regenerative engineering.
{"title":"Sr-Incorporated Bioactive Glass Remodels the Immunological Microenvironment by Enhancing the Mitochondrial Function of Macrophage via the PI3K/AKT/mTOR Signaling Pathway","authors":"Huanhuan Qiu, Huacui Xiong, Jiafu Zheng, Yuqi Peng, Chunhui Wang, Qing Hu, Fujian Zhao* and Ke Chen*, ","doi":"10.1021/acsbiomaterials.4c00228","DOIUrl":"10.1021/acsbiomaterials.4c00228","url":null,"abstract":"<p >The repair of critical-sized bone defects continues to pose a challenge in clinics. Strontium (Sr), recognized for its function in bone metabolism regulation, has shown potential in bone repair. However, the underlying mechanism through which Sr<sup>2+</sup> guided favorable osteogenesis by modulating macrophages remains unclear, limiting their application in the design of bone biomaterials. Herein, Sr-incorporated bioactive glass (SrBG) was synthesized for further investigation. The release of Sr ions enhanced the immunomodulatory properties and osteogenic potential by modulating the polarization of macrophages toward the M2 phenotype. <i>In vivo</i>, a 3D-printed SrBG scaffold was fabricated and showed consistently improved bone regeneration by creating a prohealing immunological microenvironment. RNA sequencing was performed to explore the underlying mechanisms. It was found that Sr ions might enhance the mitochondrial function of macrophage by activating PI3K/AKT/mTOR signaling, thereby favoring osteogenesis. Our findings demonstrate the relationship between the immunomodulatory role of Sr ions and the mitochondrial function of macrophages. By focusing on the mitochondrial function of macrophages, Sr<sup>2+</sup>-mediated immunomodulation sheds light on the future design of biomaterials for tissue regenerative engineering.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141064261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-16DOI: 10.1021/acsbiomaterials.4c00457
Jiaxin Hu, Jiawei Wei, Jiangshan Liu, Li Yuan, Yongzhi Li, Xue Luo, Yubao Li and Jidong Li*,
Due to the decomposition temperature of Polyamide 66 (PA66) in the environment is close to its thermoforming temperature, it is difficult to construct porous scaffolds of PA66/nanohydroxyapatite (PA66/HAp) by fused deposition modeling (FDM) three-dimensional (3D) printing. In this study, we demonstrated for the first time a method for 3D printing PA66/HAp composites at room temperature, prepared PA66/HAp printing ink using a mixed solvent of formic acid/dichloromethane (FA/DCM), and constructed a series of composite scaffolds with varying HAp content. This printing system can print composite materials with a high HAp content of 60 wt %, which is close to the mineral content in natural bone. The physicochemical evaluation presented that the hydroxyapatite was uniformly distributed within the PA66 matrix, and the PA66/HAp composite scaffold with 30 wt % HAp content exhibited optimal mechanical properties and printability. The results of in vitro cell culture experiments indicated that the incorporation of HAp into the PA66 matrix significantly improved the cell adhesion, proliferation, and osteogenic differentiation of bone marrow stromal cells (BMSCs) cultured on the scaffold. In vivo animal experiments suggested that the PA66/HAp composite material with 30 wt % HAp content had the best structural maintenance and osteogenic performance. The three-dimensional PA66/HAp composite scaffold prepared by low temperature printing in the current study holds great potential for the repair of large-area bone defects.
{"title":"A Novel Strategy for Fabrication of Polyamide 66/Nanohydroxyapatite Composite Bone Repair Scaffolds by Low-Temperature Three-Dimensional Printing","authors":"Jiaxin Hu, Jiawei Wei, Jiangshan Liu, Li Yuan, Yongzhi Li, Xue Luo, Yubao Li and Jidong Li*, ","doi":"10.1021/acsbiomaterials.4c00457","DOIUrl":"10.1021/acsbiomaterials.4c00457","url":null,"abstract":"<p >Due to the decomposition temperature of Polyamide 66 (PA66) in the environment is close to its thermoforming temperature, it is difficult to construct porous scaffolds of PA66/nanohydroxyapatite (PA66/HAp) by fused deposition modeling (FDM) three-dimensional (3D) printing. In this study, we demonstrated for the first time a method for 3D printing PA66/HAp composites at room temperature, prepared PA66/HAp printing ink using a mixed solvent of formic acid/dichloromethane (FA/DCM), and constructed a series of composite scaffolds with varying HAp content. This printing system can print composite materials with a high HAp content of 60 wt %, which is close to the mineral content in natural bone. The physicochemical evaluation presented that the hydroxyapatite was uniformly distributed within the PA66 matrix, and the PA66/HAp composite scaffold with 30 wt % HAp content exhibited optimal mechanical properties and printability. The results of in vitro cell culture experiments indicated that the incorporation of HAp into the PA66 matrix significantly improved the cell adhesion, proliferation, and osteogenic differentiation of bone marrow stromal cells (BMSCs) cultured on the scaffold. In vivo animal experiments suggested that the PA66/HAp composite material with 30 wt % HAp content had the best structural maintenance and osteogenic performance. The three-dimensional PA66/HAp composite scaffold prepared by low temperature printing in the current study holds great potential for the repair of large-area bone defects.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140943008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-16DOI: 10.1021/acsbiomaterials.3c01740
Pinky, Aarushi Sharma, Varun Arora, E. P. Rao, Sudheer Arava, A. Agrawal, M. Jassal, Sujata Mohanty
There is an arising need for effective wound dressings that retain the bioactivity of a cellular treatment, but without the high costs and complexities associated with manufacturing, storing, and applying cell-based products. As skin wound recovery is a dynamic and complicated process, a significant obstacle to the healing of skin wounds is the lack of an appropriate wound dressing that can imitate the microenvironment of healthy skin and prevent bacterial infection. It requires the well-orchestrated integration of biological and molecular events. In this study, we have fabricated full-thickness skin graft biocomposite membranes to target full-thickness skin excision wounds. We reinforced human amniotic membrane (hAM) with electrospun polycaprolactone (PCL) to develop composite membranes, namely, PCL/hAM and PCL/hAM/PCL. Composite membranes were compared for physical, biological, and mechanical properties with the native counterpart. PCL/hAM and PCL/hAM/PCL displayed improved stability and delayed degradation, which further synergically improved the rapid wound healing property of hAM, driven primarily by wound closure analysis and histological assessment. Moreover, PCL/hAM displayed a comparable cellular interaction to hAM. On application as a wound dressing, histological analysis demonstrated that hAM and PCL/hAM promoted early epidermis and dermis formation. Studies on in vivo wound healing revealed that although hAM accelerates cell development, the overall wound healing process is similar in PCL/hAM. This finding is further supported by the immunohistochemical analysis of COL-1/COL-3, CD-31, and TGF-β. Overall, this conjugated PCL and hAM-based membrane has considerable potential to be applied in skin wound healing. The facile fabrication of the PCL/hAM composite membrane provided the self-regenerating wound dressing with the desired mechanical strength as an ideal regenerative property for skin tissue regeneration.
目前需要一种有效的伤口敷料,既能保持细胞治疗的生物活性,又能避免制造、储存和应用细胞产品所带来的高成本和复杂性。由于皮肤伤口的恢复是一个动态而复杂的过程,皮肤伤口愈合的一个重要障碍是缺乏一种合适的伤口敷料,既能模仿健康皮肤的微环境,又能防止细菌感染。这需要对生物和分子事件进行精心策划的整合。在这项研究中,我们针对全厚皮肤切除伤口制作了全厚皮肤移植生物复合膜。我们用电纺聚己内酯(PCL)增强了人羊膜(hAM),从而开发出复合膜,即 PCL/hAM 和 PCL/hAM/PCL。复合膜的物理、生物和机械性能与原生膜进行了比较。PCL/hAM 和 PCL/hAM/PCL 显示出更高的稳定性和延迟降解性,这进一步协同改善了 hAM 的快速伤口愈合特性,这主要是通过伤口闭合分析和组织学评估来实现的。此外,PCL/hAM 显示出与 hAM 相似的细胞相互作用。在用作伤口敷料时,组织学分析表明 hAM 和 PCL/hAM 促进了早期表皮和真皮的形成。对体内伤口愈合的研究表明,虽然 hAM 能加速细胞发育,但 PCL/hAM 的整体伤口愈合过程与之相似。对 COL-1/COL-3、CD-31 和 TGF-β 的免疫组化分析进一步证实了这一结论。总之,这种基于 PCL 和 hAM 的共轭膜在皮肤伤口愈合方面具有相当大的应用潜力。PCL/hAM 复合膜的简易制备为自再生伤口敷料提供了所需的机械强度,这是皮肤组织再生的理想再生特性。
{"title":"Modulating the hAM/PCL Biocomposite for Expedited Wound Healing: A Chemical-Free Approach for Boosting Regenerative Potential.","authors":"Pinky, Aarushi Sharma, Varun Arora, E. P. Rao, Sudheer Arava, A. Agrawal, M. Jassal, Sujata Mohanty","doi":"10.1021/acsbiomaterials.3c01740","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.3c01740","url":null,"abstract":"There is an arising need for effective wound dressings that retain the bioactivity of a cellular treatment, but without the high costs and complexities associated with manufacturing, storing, and applying cell-based products. As skin wound recovery is a dynamic and complicated process, a significant obstacle to the healing of skin wounds is the lack of an appropriate wound dressing that can imitate the microenvironment of healthy skin and prevent bacterial infection. It requires the well-orchestrated integration of biological and molecular events. In this study, we have fabricated full-thickness skin graft biocomposite membranes to target full-thickness skin excision wounds. We reinforced human amniotic membrane (hAM) with electrospun polycaprolactone (PCL) to develop composite membranes, namely, PCL/hAM and PCL/hAM/PCL. Composite membranes were compared for physical, biological, and mechanical properties with the native counterpart. PCL/hAM and PCL/hAM/PCL displayed improved stability and delayed degradation, which further synergically improved the rapid wound healing property of hAM, driven primarily by wound closure analysis and histological assessment. Moreover, PCL/hAM displayed a comparable cellular interaction to hAM. On application as a wound dressing, histological analysis demonstrated that hAM and PCL/hAM promoted early epidermis and dermis formation. Studies on in vivo wound healing revealed that although hAM accelerates cell development, the overall wound healing process is similar in PCL/hAM. This finding is further supported by the immunohistochemical analysis of COL-1/COL-3, CD-31, and TGF-β. Overall, this conjugated PCL and hAM-based membrane has considerable potential to be applied in skin wound healing. The facile fabrication of the PCL/hAM composite membrane provided the self-regenerating wound dressing with the desired mechanical strength as an ideal regenerative property for skin tissue regeneration.","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140968837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-16DOI: 10.1021/acsbiomaterials.3c01740
Pinky, Aarushi Sharma, Varun Arora, E Pranshu Rao, Sudheer Arava, Ashwini K Agrawal, Manjeet Jassal and Sujata Mohanty*,
There is an arising need for effective wound dressings that retain the bioactivity of a cellular treatment, but without the high costs and complexities associated with manufacturing, storing, and applying cell-based products. As skin wound recovery is a dynamic and complicated process, a significant obstacle to the healing of skin wounds is the lack of an appropriate wound dressing that can imitate the microenvironment of healthy skin and prevent bacterial infection. It requires the well-orchestrated integration of biological and molecular events. In this study, we have fabricated full-thickness skin graft biocomposite membranes to target full-thickness skin excision wounds. We reinforced human amniotic membrane (hAM) with electrospun polycaprolactone (PCL) to develop composite membranes, namely, PCL/hAM and PCL/hAM/PCL. Composite membranes were compared for physical, biological, and mechanical properties with the native counterpart. PCL/hAM and PCL/hAM/PCL displayed improved stability and delayed degradation, which further synergically improved the rapid wound healing property of hAM, driven primarily by wound closure analysis and histological assessment. Moreover, PCL/hAM displayed a comparable cellular interaction to hAM. On application as a wound dressing, histological analysis demonstrated that hAM and PCL/hAM promoted early epidermis and dermis formation. Studies on in vivo wound healing revealed that although hAM accelerates cell development, the overall wound healing process is similar in PCL/hAM. This finding is further supported by the immunohistochemical analysis of COL-1/COL-3, CD-31, and TGF-β. Overall, this conjugated PCL and hAM-based membrane has considerable potential to be applied in skin wound healing. The facile fabrication of the PCL/hAM composite membrane provided the self-regenerating wound dressing with the desired mechanical strength as an ideal regenerative property for skin tissue regeneration.
目前需要一种有效的伤口敷料,既能保持细胞治疗的生物活性,又能避免制造、储存和应用细胞产品所带来的高成本和复杂性。由于皮肤伤口的恢复是一个动态而复杂的过程,皮肤伤口愈合的一个重要障碍是缺乏一种合适的伤口敷料,既能模仿健康皮肤的微环境,又能防止细菌感染。这需要对生物和分子事件进行精心策划的整合。在这项研究中,我们针对全厚皮肤切除伤口制作了全厚皮肤移植生物复合膜。我们用电纺聚己内酯(PCL)增强了人羊膜(hAM),从而开发出复合膜,即 PCL/hAM 和 PCL/hAM/PCL。复合膜的物理、生物和机械性能与原生膜进行了比较。PCL/hAM 和 PCL/hAM/PCL 显示出更高的稳定性和延迟降解性,这进一步协同改善了 hAM 的快速伤口愈合特性,这主要是通过伤口闭合分析和组织学评估来实现的。此外,PCL/hAM 显示出与 hAM 相似的细胞相互作用。在用作伤口敷料时,组织学分析表明 hAM 和 PCL/hAM 促进了早期表皮和真皮的形成。对体内伤口愈合的研究表明,虽然 hAM 能加速细胞发育,但 PCL/hAM 的整体伤口愈合过程与之相似。对 COL-1/COL-3、CD-31 和 TGF-β 的免疫组化分析进一步证实了这一结论。总之,这种基于 PCL 和 hAM 的共轭膜在皮肤伤口愈合方面具有相当大的应用潜力。PCL/hAM 复合膜的简易制备为自再生伤口敷料提供了所需的机械强度,这是皮肤组织再生的理想再生特性。
{"title":"Modulating the hAM/PCL Biocomposite for Expedited Wound Healing: A Chemical-Free Approach for Boosting Regenerative Potential","authors":"Pinky, Aarushi Sharma, Varun Arora, E Pranshu Rao, Sudheer Arava, Ashwini K Agrawal, Manjeet Jassal and Sujata Mohanty*, ","doi":"10.1021/acsbiomaterials.3c01740","DOIUrl":"10.1021/acsbiomaterials.3c01740","url":null,"abstract":"<p >There is an arising need for effective wound dressings that retain the bioactivity of a cellular treatment, but without the high costs and complexities associated with manufacturing, storing, and applying cell-based products. As skin wound recovery is a dynamic and complicated process, a significant obstacle to the healing of skin wounds is the lack of an appropriate wound dressing that can imitate the microenvironment of healthy skin and prevent bacterial infection. It requires the well-orchestrated integration of biological and molecular events. In this study, we have fabricated full-thickness skin graft biocomposite membranes to target full-thickness skin excision wounds. We reinforced human amniotic membrane (hAM) with electrospun polycaprolactone (PCL) to develop composite membranes, namely, PCL/hAM and PCL/hAM/PCL. Composite membranes were compared for physical, biological, and mechanical properties with the native counterpart. PCL/hAM and PCL/hAM/PCL displayed improved stability and delayed degradation, which further synergically improved the rapid wound healing property of hAM, driven primarily by wound closure analysis and histological assessment. Moreover, PCL/hAM displayed a comparable cellular interaction to hAM. On application as a wound dressing, histological analysis demonstrated that hAM and PCL/hAM promoted early epidermis and dermis formation. Studies on <i>in vivo</i> wound healing revealed that although hAM accelerates cell development, the overall wound healing process is similar in PCL/hAM. This finding is further supported by the immunohistochemical analysis of COL-1/COL-3, CD-31, and TGF-β. Overall, this conjugated PCL and hAM-based membrane has considerable potential to be applied in skin wound healing. The facile fabrication of the PCL/hAM composite membrane provided the self-regenerating wound dressing with the desired mechanical strength as an ideal regenerative property for skin tissue regeneration.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140961494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-16DOI: 10.1021/acsbiomaterials.3c01579
Simone A. Douglas-Green, Juan A. Aleman and Paula T. Hammond*,
Improving the clinical translation of nanomedicine requires better knowledge about how nanoparticles interact with biological environments. As researchers are recognizing the importance of understanding the protein corona and characterizing how nanocarriers respond in biological systems, new tools and techniques are needed to analyze nanocarrier–protein interactions, especially for smaller size (<10 nm) nanoparticles like polyamidoamine (PAMAM) dendrimers. Here, we developed a streamlined, semiquantitative approach to assess dendrimer–protein interactions using a nondenaturing electrophoresis technique combined with mass spectrometry. With this protocol, we detect fluorescently tagged dendrimers and proteins simultaneously, enabling us to analyze when dendrimers migrate with proteins. We found that PAMAM dendrimers mostly interact with complement proteins, particularly C3 and C4a, which aligns with previously published data, verifying that our approach can be used to isolate and identify dendrimer–protein interactions.
{"title":"Electrophoresis-Based Approach for Characterizing Dendrimer–Protein Interactions: A Proof-of-Concept Study","authors":"Simone A. Douglas-Green, Juan A. Aleman and Paula T. Hammond*, ","doi":"10.1021/acsbiomaterials.3c01579","DOIUrl":"10.1021/acsbiomaterials.3c01579","url":null,"abstract":"<p >Improving the clinical translation of nanomedicine requires better knowledge about how nanoparticles interact with biological environments. As researchers are recognizing the importance of understanding the protein corona and characterizing how nanocarriers respond in biological systems, new tools and techniques are needed to analyze nanocarrier–protein interactions, especially for smaller size (<10 nm) nanoparticles like polyamidoamine (PAMAM) dendrimers. Here, we developed a streamlined, semiquantitative approach to assess dendrimer–protein interactions using a nondenaturing electrophoresis technique combined with mass spectrometry. With this protocol, we detect fluorescently tagged dendrimers and proteins simultaneously, enabling us to analyze when dendrimers migrate with proteins. We found that PAMAM dendrimers mostly interact with complement proteins, particularly C3 and C4a, which aligns with previously published data, verifying that our approach can be used to isolate and identify dendrimer–protein interactions.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140961493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}