Pub Date : 2024-07-19DOI: 10.3389/fbiom.2024.1455984
Chun Wang, Virginia Brancato
{"title":"Editorial: Celebrating 1 year of frontiers in biomaterials science","authors":"Chun Wang, Virginia Brancato","doi":"10.3389/fbiom.2024.1455984","DOIUrl":"https://doi.org/10.3389/fbiom.2024.1455984","url":null,"abstract":"","PeriodicalId":73067,"journal":{"name":"Frontiers in biomaterials science","volume":" 742","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141823438","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 : 2024-07-15DOI: 10.3389/fbiom.2024.1408748
Eya Ferchichi, Samuel T Stealey, Paige Bogert, S. Zustiak
Three-dimensional (3D) tissue-engineered scaffolds mimic the physiological environment of cells by providing essential structural support, biochemical cues, and the mechanical strength needed for cell adhesion, proliferation, migration, and differentiation. Hydrogels like polyethylene glycol diacrylate (PEGDA) are commonly used biomaterials for cell culture due to their affordability, tunable stiffness, and ability to efficiently transport nutrients and gases. However, PEGDA lacks cell adhesion sites essential for cell proliferation and migration and has limited degradability. Methacrylated gelatin (GelMA) produced from denatured bovine collagen, crosslinks under ultraviolet light (UV) resulting in a degradable hydrogel with cell adhesion sites. Here, we synthesized GelMA with variable degree of methacrylation and crosslinked it with PEGDA to produce cell scaffolds with independently tunable mechanical and biochemical properties by varying the ratios of the two polymers. We determined polymer ratios that resulted in scaffolds with different mechanical properties but the same gelatin concentrations (providing cell adhesion and degradation sites) as well as different gelatin concentrations but the same mechanical properties. With the developed scaffold library, we further used a design of experiments approach to probe the parameter space and perform detailed analysis on chemical composition-scaffold properties as well as scaffold properties-cell behavior correlations. Our findings showed that hydrogel properties such as modulus, swelling, pore size, and permeability, strongly depended on total polymer concentration and not on the GelMA fraction. GelMA significantly influenced cell spreading, while addition of any amount of PEGDA delayed cell spreading significantly. We suggest that such analysis will broaden the utility of the GelMA/PEGDA hydrogels, presenting a versatile platform for mechanosensing research in 3D environments.
{"title":"Tunable gelatin methacrylate polyethylene glycol diacrylate hydrogels for cell mechanosensing applications","authors":"Eya Ferchichi, Samuel T Stealey, Paige Bogert, S. Zustiak","doi":"10.3389/fbiom.2024.1408748","DOIUrl":"https://doi.org/10.3389/fbiom.2024.1408748","url":null,"abstract":"Three-dimensional (3D) tissue-engineered scaffolds mimic the physiological environment of cells by providing essential structural support, biochemical cues, and the mechanical strength needed for cell adhesion, proliferation, migration, and differentiation. Hydrogels like polyethylene glycol diacrylate (PEGDA) are commonly used biomaterials for cell culture due to their affordability, tunable stiffness, and ability to efficiently transport nutrients and gases. However, PEGDA lacks cell adhesion sites essential for cell proliferation and migration and has limited degradability. Methacrylated gelatin (GelMA) produced from denatured bovine collagen, crosslinks under ultraviolet light (UV) resulting in a degradable hydrogel with cell adhesion sites. Here, we synthesized GelMA with variable degree of methacrylation and crosslinked it with PEGDA to produce cell scaffolds with independently tunable mechanical and biochemical properties by varying the ratios of the two polymers. We determined polymer ratios that resulted in scaffolds with different mechanical properties but the same gelatin concentrations (providing cell adhesion and degradation sites) as well as different gelatin concentrations but the same mechanical properties. With the developed scaffold library, we further used a design of experiments approach to probe the parameter space and perform detailed analysis on chemical composition-scaffold properties as well as scaffold properties-cell behavior correlations. Our findings showed that hydrogel properties such as modulus, swelling, pore size, and permeability, strongly depended on total polymer concentration and not on the GelMA fraction. GelMA significantly influenced cell spreading, while addition of any amount of PEGDA delayed cell spreading significantly. We suggest that such analysis will broaden the utility of the GelMA/PEGDA hydrogels, presenting a versatile platform for mechanosensing research in 3D environments.","PeriodicalId":73067,"journal":{"name":"Frontiers in biomaterials science","volume":"51 24","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141648974","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 : 2024-07-12DOI: 10.3389/fbiom.2024.1380153
Cong Wang, Tian Xu, C. Seneviratne, Louis Jun Ye Ong, Yinghong Zhou
Periodontitis is a chronic inflammatory disease associated with dysbiosis in subgingival plaque biofilm, characterised by damage to the periodontal tissues, eventually leading to tooth loss. Hence, the pathophysiology of periodontitis and interaction between subgingival plaque and host tissue under various environmental cues are central to the pathogenesis of periodontitis. Therefore, engineering biofilm models that mimic in vivo pathophysiology is crucial to obtaining a clear insight into the pathology and developing targeted therapeutic methods. In this review, we provide a comprehensive overview of the engineering strategies employed of modelling oral biofilms focusing on surface attachment, fluid microenvironment, gas environment, shear force, microbial-host interaction and offer insights into the ongoing challenges and future perspectives, which will enable the development of novel physiological relevant models for oral biofilms.
{"title":"Modelling periodontitis in vitro: engineering strategies and biofilm model development","authors":"Cong Wang, Tian Xu, C. Seneviratne, Louis Jun Ye Ong, Yinghong Zhou","doi":"10.3389/fbiom.2024.1380153","DOIUrl":"https://doi.org/10.3389/fbiom.2024.1380153","url":null,"abstract":"Periodontitis is a chronic inflammatory disease associated with dysbiosis in subgingival plaque biofilm, characterised by damage to the periodontal tissues, eventually leading to tooth loss. Hence, the pathophysiology of periodontitis and interaction between subgingival plaque and host tissue under various environmental cues are central to the pathogenesis of periodontitis. Therefore, engineering biofilm models that mimic in vivo pathophysiology is crucial to obtaining a clear insight into the pathology and developing targeted therapeutic methods. In this review, we provide a comprehensive overview of the engineering strategies employed of modelling oral biofilms focusing on surface attachment, fluid microenvironment, gas environment, shear force, microbial-host interaction and offer insights into the ongoing challenges and future perspectives, which will enable the development of novel physiological relevant models for oral biofilms.","PeriodicalId":73067,"journal":{"name":"Frontiers in biomaterials science","volume":"38 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141653868","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 : 2024-05-22DOI: 10.3389/fbiom.2024.1399448
Jodi Graf, Kartik Bomb, Michael Trautmann-Rodriguez, Bader M. Jarai, Nicole Gill, April M. Kloxin, C. Fromen
Macrophages are phagocytic innate immune cells capable of phenotypical switching in response to the local microenvironment. Studies often use either primary macrophages or immortalized cell lines for hypothesis testing, therapeutic assessment, and biomaterial evaluation without carefully considering the potential effects of cell source and tissue of origin, which strongly influence macrophage response. Surprisingly, limited information is available about how, under similar stimuli, immortalized cell lines and primary cells respond in both phenotypical and functional changes. To address this need, in this work, we cultured immortalized macrophage cell lines derived from different origins (i.e., blood, lung, peritoneal) to understand and compare macrophage phenotypical responses, including polarization and plasticity, morphological changes, and phagocytic functionalities, as well as compared primary macrophages extracted from peritoneal and bone marrow to their immortalized cell line counterparts. We found significant differences in baseline expression of different markers (e.g., CD86, MHCII, CD206, and EGR2) amongst different cell lines, which further influence both polarization and repolarization of the cells, in addition to their phagocytic functionality. Additionally, we observed that, while RAW 264.7 cells behave similarly to the primary bone marrow-derived macrophages, there are noticeable phenotypical and functional differences in cell line (IC-21) and primary peritoneal macrophages, highlighting tissue-specific differences in macrophage response amongst cell lines and primary cells. Moving to three-dimensional (3D) culture in well-defined biomaterials, blood-derived primary and cell line macrophages were encapsulated within hydrogel-based synthetic extracellular matrices and their polarization profiles and cell morphologies were compared. Macrophages exhibited less pronounced polarization during 3D culture in these compliant, soft materials compared to two-dimensional (2D) culture on rigid, tissue culture plastic plates. Overall, our findings highlight origin-specific differences in macrophage response, and therefore, careful considerations must be made to identify the appropriate cell source for the application of interest.
巨噬细胞是一种吞噬性先天性免疫细胞,能够根据局部微环境的变化进行表型转换。研究通常使用原代巨噬细胞或永生化细胞系进行假设检验、治疗评估和生物材料评价,而没有仔细考虑细胞来源和原发组织的潜在影响,因为它们对巨噬细胞的反应有很大影响。令人惊讶的是,关于在类似刺激下,永生化细胞系和原代细胞如何在表型和功能变化方面做出反应的信息非常有限。为了满足这一需求,在这项工作中,我们培养了来自不同来源(如血液、肺、腹膜)的永生化巨噬细胞系,以了解和比较巨噬细胞的表型反应,包括极化和可塑性、形态变化和吞噬功能,并将从腹膜和骨髓中提取的原代巨噬细胞与其永生化细胞系进行比较。我们发现,不同细胞系之间不同标记物(如 CD86、MHCII、CD206 和 EGR2)的基线表达存在明显差异,这进一步影响了细胞的极化和再极化,以及它们的吞噬功能。此外,我们还观察到,虽然 RAW 264.7 细胞的行为与原代骨髓巨噬细胞相似,但细胞系(IC-21)和原代腹膜巨噬细胞在表型和功能上存在明显差异,这突显了细胞系和原代细胞之间巨噬细胞反应的组织特异性差异。在定义明确的生物材料中进行三维(3D)培养时,将源自血液的原代巨噬细胞和细胞系巨噬细胞封装在基于水凝胶的合成细胞外基质中,并比较它们的极化特征和细胞形态。与在刚性组织培养塑料板上进行二维(2D)培养相比,巨噬细胞在这些顺应性软材料的三维培养过程中表现出的极化不那么明显。总之,我们的研究结果凸显了巨噬细胞反应的来源特异性差异,因此必须仔细考虑为相关应用确定合适的细胞来源。
{"title":"Macrophage variance: investigating how macrophage origin influences responses to soluble and physical cues with immortalized vs. primary cells in 2D and 3D culture","authors":"Jodi Graf, Kartik Bomb, Michael Trautmann-Rodriguez, Bader M. Jarai, Nicole Gill, April M. Kloxin, C. Fromen","doi":"10.3389/fbiom.2024.1399448","DOIUrl":"https://doi.org/10.3389/fbiom.2024.1399448","url":null,"abstract":"Macrophages are phagocytic innate immune cells capable of phenotypical switching in response to the local microenvironment. Studies often use either primary macrophages or immortalized cell lines for hypothesis testing, therapeutic assessment, and biomaterial evaluation without carefully considering the potential effects of cell source and tissue of origin, which strongly influence macrophage response. Surprisingly, limited information is available about how, under similar stimuli, immortalized cell lines and primary cells respond in both phenotypical and functional changes. To address this need, in this work, we cultured immortalized macrophage cell lines derived from different origins (i.e., blood, lung, peritoneal) to understand and compare macrophage phenotypical responses, including polarization and plasticity, morphological changes, and phagocytic functionalities, as well as compared primary macrophages extracted from peritoneal and bone marrow to their immortalized cell line counterparts. We found significant differences in baseline expression of different markers (e.g., CD86, MHCII, CD206, and EGR2) amongst different cell lines, which further influence both polarization and repolarization of the cells, in addition to their phagocytic functionality. Additionally, we observed that, while RAW 264.7 cells behave similarly to the primary bone marrow-derived macrophages, there are noticeable phenotypical and functional differences in cell line (IC-21) and primary peritoneal macrophages, highlighting tissue-specific differences in macrophage response amongst cell lines and primary cells. Moving to three-dimensional (3D) culture in well-defined biomaterials, blood-derived primary and cell line macrophages were encapsulated within hydrogel-based synthetic extracellular matrices and their polarization profiles and cell morphologies were compared. Macrophages exhibited less pronounced polarization during 3D culture in these compliant, soft materials compared to two-dimensional (2D) culture on rigid, tissue culture plastic plates. Overall, our findings highlight origin-specific differences in macrophage response, and therefore, careful considerations must be made to identify the appropriate cell source for the application of interest.","PeriodicalId":73067,"journal":{"name":"Frontiers in biomaterials science","volume":"68 23","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141110194","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 : 2024-05-10DOI: 10.3389/fbiom.2024.1323763
Lu Luo, Kerime Ebrar Okur, P. Bagnaninchi, Alicia J. El Haj
The mechanical performance of tissue-engineered grafts is crucial in determining their functional properties, integration with native tissue and long-term repair outcome post-implantation. To date, most approaches for testing the mechanical properties of tissue-engineered grafts are non-sterile and invasive. There is an urgent need to develop novel sterile approaches for online monitoring mechanical properties of engineered tissues in order to ensure these engineered products meet the desired mechanical strength prior to implantation. In this paper, we overview various approaches for mechanical testing of engineered tissues, which span from traditional methods to medical imaging concepts in magnetic resonance elastography, ultrasound elastography, and optical coherence elastography. We focused on the applicability of these methods to the manufacturing of tissue-engineered products online, e.g., if such approach provides a sterile monitoring capacity and is capable of defining mechanical heterogeneity in engineered tissues throughout their growth in vitro in real-time. The review delves into various imaging modalities that employ distinct methods for inducing displacement within the sample, utilizing either strain-based or shear wave-based approaches. This displacement can be achieved through external stimulation or by harnessing ambient vibrations. Subsequently, the imaging process captures and visualizes the resultant displacement. We specifically highlight the advantages of novel non-invasive imaging methods such as ultrasound elastography and optical coherence elastography to assess the mechanical properties of engineered tissues in vitro, as well as their potential applications in cancer study, drug screening and the in vivo evaluation of the engineered tissues.
{"title":"Current challenges in imaging the mechanical properties of tissue engineered grafts","authors":"Lu Luo, Kerime Ebrar Okur, P. Bagnaninchi, Alicia J. El Haj","doi":"10.3389/fbiom.2024.1323763","DOIUrl":"https://doi.org/10.3389/fbiom.2024.1323763","url":null,"abstract":"The mechanical performance of tissue-engineered grafts is crucial in determining their functional properties, integration with native tissue and long-term repair outcome post-implantation. To date, most approaches for testing the mechanical properties of tissue-engineered grafts are non-sterile and invasive. There is an urgent need to develop novel sterile approaches for online monitoring mechanical properties of engineered tissues in order to ensure these engineered products meet the desired mechanical strength prior to implantation. In this paper, we overview various approaches for mechanical testing of engineered tissues, which span from traditional methods to medical imaging concepts in magnetic resonance elastography, ultrasound elastography, and optical coherence elastography. We focused on the applicability of these methods to the manufacturing of tissue-engineered products online, e.g., if such approach provides a sterile monitoring capacity and is capable of defining mechanical heterogeneity in engineered tissues throughout their growth in vitro in real-time. The review delves into various imaging modalities that employ distinct methods for inducing displacement within the sample, utilizing either strain-based or shear wave-based approaches. This displacement can be achieved through external stimulation or by harnessing ambient vibrations. Subsequently, the imaging process captures and visualizes the resultant displacement. We specifically highlight the advantages of novel non-invasive imaging methods such as ultrasound elastography and optical coherence elastography to assess the mechanical properties of engineered tissues in vitro, as well as their potential applications in cancer study, drug screening and the in vivo evaluation of the engineered tissues.","PeriodicalId":73067,"journal":{"name":"Frontiers in biomaterials science","volume":" 19","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140993894","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 : 2024-04-03DOI: 10.3389/fbiom.2024.1358508
Nikhith Kalkunte, Jorge Cisneros, Edward Castillo, Janet Zoldan
Cardiac tissue engineering (CTE) holds promise in addressing the clinical challenges posed by cardiovascular disease, the leading global cause of mortality. Human induced pluripotent stem cells (hiPSCs) are pivotal for cardiac regeneration therapy, offering an immunocompatible, high density cell source. However, hiPSC-derived cardiomyocytes (hiPSC-CMs) exhibit vital functional deficiencies that are not yet well understood, hindering their clinical deployment. We argue that machine learning (ML) can overcome these challenges, by improving the phenotyping and functionality of these cells via robust mathematical models and predictions. This review paper explores the transformative role of ML in advancing CTE, presenting a primer on relevant ML algorithms. We focus on how ML has recently addressed six key address six key challenges in CTE: cell differentiation, morphology, calcium handling and cell-cell coupling, contraction, and tissue assembly. The paper surveys common ML models, from tree-based and probabilistic to neural networks and deep learning, illustrating their applications to better understand hiPSC-CM behavior. While acknowledging the challenges associated with integrating ML, such as limited biomedical datasets, computational costs of learning data, and model interpretability and reliability, we examine suggestions for improvement, emphasizing the necessity for more extensive and diverse datasets that incorporate temporal and imaging data, augmented by synthetic generative models. By integrating ML with mathematical models and existing expert knowledge, we foresee a fruitful collaboration that unites innovative data-driven models with biophysics-informed models, effectively closing the gaps within CTE.
心脏组织工程(CTE)有望应对心血管疾病这一全球主要死亡原因所带来的临床挑战。人类诱导多能干细胞(hiPSC)是心脏再生治疗的关键,它提供了一种免疫兼容的高密度细胞来源。然而,hiPSC 衍生的心肌细胞(hiPSC-CMs)表现出重要的功能缺陷,这些缺陷尚未得到很好的了解,阻碍了其临床应用。我们认为,机器学习(ML)可以通过强大的数学模型和预测改善这些细胞的表型和功能,从而克服这些挑战。本综述论文探讨了 ML 在推动 CTE 方面的变革性作用,并介绍了相关的 ML 算法。我们重点关注 ML 最近是如何解决 CTE 中的六个关键难题的:细胞分化、形态、钙处理和细胞-细胞耦合、收缩和组织组装。论文介绍了常见的 ML 模型,从基于树的模型、概率模型到神经网络和深度学习模型,说明了它们在更好地理解 hiPSC-CM 行为方面的应用。我们承认整合 ML 所面临的挑战,如有限的生物医学数据集、学习数据的计算成本以及模型的可解释性和可靠性等,同时我们还研究了改进建议,强调需要更广泛、更多样的数据集,其中包括时间和成像数据,并通过合成生成模型加以扩充。通过将 ML 与数学模型和现有的专家知识相结合,我们预见到将创新的数据驱动模型与生物物理学信息模型结合起来的合作会取得丰硕成果,从而有效缩小 CTE 的差距。
{"title":"A review on machine learning approaches in cardiac tissue engineering","authors":"Nikhith Kalkunte, Jorge Cisneros, Edward Castillo, Janet Zoldan","doi":"10.3389/fbiom.2024.1358508","DOIUrl":"https://doi.org/10.3389/fbiom.2024.1358508","url":null,"abstract":"Cardiac tissue engineering (CTE) holds promise in addressing the clinical challenges posed by cardiovascular disease, the leading global cause of mortality. Human induced pluripotent stem cells (hiPSCs) are pivotal for cardiac regeneration therapy, offering an immunocompatible, high density cell source. However, hiPSC-derived cardiomyocytes (hiPSC-CMs) exhibit vital functional deficiencies that are not yet well understood, hindering their clinical deployment. We argue that machine learning (ML) can overcome these challenges, by improving the phenotyping and functionality of these cells via robust mathematical models and predictions. This review paper explores the transformative role of ML in advancing CTE, presenting a primer on relevant ML algorithms. We focus on how ML has recently addressed six key address six key challenges in CTE: cell differentiation, morphology, calcium handling and cell-cell coupling, contraction, and tissue assembly. The paper surveys common ML models, from tree-based and probabilistic to neural networks and deep learning, illustrating their applications to better understand hiPSC-CM behavior. While acknowledging the challenges associated with integrating ML, such as limited biomedical datasets, computational costs of learning data, and model interpretability and reliability, we examine suggestions for improvement, emphasizing the necessity for more extensive and diverse datasets that incorporate temporal and imaging data, augmented by synthetic generative models. By integrating ML with mathematical models and existing expert knowledge, we foresee a fruitful collaboration that unites innovative data-driven models with biophysics-informed models, effectively closing the gaps within CTE.","PeriodicalId":73067,"journal":{"name":"Frontiers in biomaterials science","volume":"67 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140747647","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 : 2024-04-03DOI: 10.3389/fbiom.2024.1360443
Emmanuel Einyat Opolot, Haochen Wang, J. Capadona, Horst A. von Recum, Hoda Amani Hamedani
Introduction: Implantable medical devices continue to be vulnerable to bacterial infections. The unrelenting formation of antibiotic resistant bacterial strains not only exacerbates these infections but also renders the current treatment strategies impotent. The need is greater than ever for innovative and effective approaches to counteract drug-resistant bacteria. This study examines the innate antibacterial properties of TiO2 nanotube arrays (TNAs) and their ability to locally deliver antibiotics to inactivate gram-positive and gram-negative bacteria, in vitro.Methods: Using a two-step electrochemical anodization process, TNAs with a diameter of ∼100 nm and a length of ∼5 µm were grown on titanium substrates.Results and Discussion: After 24 h of incubation, as-fabricated TNAs showed 100% clearance of Escherichia coli, and 97% clearance of Staphylococcus aureus growth. The antibiotic-loaded TNAs demonstrated sustained slow-release of cefotaxime and imipenem measured over 14 days. In vitro bacterial studies revealed the capability of cefotaxime- and imipenem-loaded TNAs in completely inhibiting the growth with 100% clearance of Klebsiella pneumoniae after 24 and 48 h of incubation. Bacterial inhibition assay revealed a significantly enlarged inhibition zone difference of 18 mm around the imipenem-loaded TNAs against K. pneumoniae compared to the as-fabricated TNAs which was maintained for 7 days with ∼10 μgmL−1 of antibiotic released from the TNAs which was found to be lower than the dose required to completely eradicate multidrug resistant bacteria when used in conjunction with the antibacterial TNAs. The results of our study highlight the potential of TNAs as a versatile platform for addressing treatment strategies related to bacterial infections and antibiotic resistance in implantable medical devices.
{"title":"Synergistic antibacterial activity and inhibition of TiO2 nanotube arrays and loaded antibiotics against gram-positive and gram-negative bacteria","authors":"Emmanuel Einyat Opolot, Haochen Wang, J. Capadona, Horst A. von Recum, Hoda Amani Hamedani","doi":"10.3389/fbiom.2024.1360443","DOIUrl":"https://doi.org/10.3389/fbiom.2024.1360443","url":null,"abstract":"Introduction: Implantable medical devices continue to be vulnerable to bacterial infections. The unrelenting formation of antibiotic resistant bacterial strains not only exacerbates these infections but also renders the current treatment strategies impotent. The need is greater than ever for innovative and effective approaches to counteract drug-resistant bacteria. This study examines the innate antibacterial properties of TiO2 nanotube arrays (TNAs) and their ability to locally deliver antibiotics to inactivate gram-positive and gram-negative bacteria, in vitro.Methods: Using a two-step electrochemical anodization process, TNAs with a diameter of ∼100 nm and a length of ∼5 µm were grown on titanium substrates.Results and Discussion: After 24 h of incubation, as-fabricated TNAs showed 100% clearance of Escherichia coli, and 97% clearance of Staphylococcus aureus growth. The antibiotic-loaded TNAs demonstrated sustained slow-release of cefotaxime and imipenem measured over 14 days. In vitro bacterial studies revealed the capability of cefotaxime- and imipenem-loaded TNAs in completely inhibiting the growth with 100% clearance of Klebsiella pneumoniae after 24 and 48 h of incubation. Bacterial inhibition assay revealed a significantly enlarged inhibition zone difference of 18 mm around the imipenem-loaded TNAs against K. pneumoniae compared to the as-fabricated TNAs which was maintained for 7 days with ∼10 μgmL−1 of antibiotic released from the TNAs which was found to be lower than the dose required to completely eradicate multidrug resistant bacteria when used in conjunction with the antibacterial TNAs. The results of our study highlight the potential of TNAs as a versatile platform for addressing treatment strategies related to bacterial infections and antibiotic resistance in implantable medical devices.","PeriodicalId":73067,"journal":{"name":"Frontiers in biomaterials science","volume":"227 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140746558","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 : 2024-03-27DOI: 10.3389/fbiom.2024.1347324
Lorna Westwood, Iain J. Nixon, Elaine Emmerson, Anthony Callanan
Cancer affects tens of millions of the world’s population each year with a stark mortality rate. It is well established that in order to be effective in treating solid tumor cancers, the current treatment methods used often sacrifice surrounding healthy tissue and cause damage at the site of treatment, inducing changes to the surrounding microenvironment. These changes to the microenvironment can lead to adverse side effects as well as long-term damage which continues to have a detrimental impact on the patient’s quality of life, even after remission. It is believed that by modulating the tumor microenvironment (TME) post-treatment, not only may the efficacy of current treatments be improved, but such associated negative side effects, as well as further complications arising from treatment, including metastasis, have the potential to be reduced. Mediating the microenvironment is also considered to aid in repairing the damaged site post-treatment, subsequently making the conditions more favourable for promoting regenerative processes. This review provides a brief overview of the alterations in the TME resulting from the three main cancer treatments–chemotherapy, radiation therapy and surgery–and the most common tissue engineering methods currently used in an attempt to mediate the TME post-cancer therapy. Furthermore, it investigates new emerging technologies within this field and the progress of such methods in terms of reaching the clinical setting.
{"title":"The road after cancer: biomaterials and tissue engineering approaches to mediate the tumor microenvironment post-cancer treatment","authors":"Lorna Westwood, Iain J. Nixon, Elaine Emmerson, Anthony Callanan","doi":"10.3389/fbiom.2024.1347324","DOIUrl":"https://doi.org/10.3389/fbiom.2024.1347324","url":null,"abstract":"Cancer affects tens of millions of the world’s population each year with a stark mortality rate. It is well established that in order to be effective in treating solid tumor cancers, the current treatment methods used often sacrifice surrounding healthy tissue and cause damage at the site of treatment, inducing changes to the surrounding microenvironment. These changes to the microenvironment can lead to adverse side effects as well as long-term damage which continues to have a detrimental impact on the patient’s quality of life, even after remission. It is believed that by modulating the tumor microenvironment (TME) post-treatment, not only may the efficacy of current treatments be improved, but such associated negative side effects, as well as further complications arising from treatment, including metastasis, have the potential to be reduced. Mediating the microenvironment is also considered to aid in repairing the damaged site post-treatment, subsequently making the conditions more favourable for promoting regenerative processes. This review provides a brief overview of the alterations in the TME resulting from the three main cancer treatments–chemotherapy, radiation therapy and surgery–and the most common tissue engineering methods currently used in an attempt to mediate the TME post-cancer therapy. Furthermore, it investigates new emerging technologies within this field and the progress of such methods in terms of reaching the clinical setting.","PeriodicalId":73067,"journal":{"name":"Frontiers in biomaterials science","volume":"85 19","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140376156","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 : 2024-02-06DOI: 10.3389/fbiom.2024.1331032
G. Lindberg, A. Norberg, B. Soliman, T. Jüngst, K. Lim, G. Hooper, J. Groll, T. Woodfield
The intricate nature of native cartilage, characterized by zonal variations in oxygen levels and ECM composition, poses a challenge for existing hydrogel-based tissue models. Consequently, these 3D models often present simplified renditions of the native tissue, failing to fully capture its heterogenous nature. The combined effects of hydrogel components, network properties, and structural designs on cellular responses are often overlooked. In this work, we aim to establish more physiological cartilage models through biofabrication of photopolymerizable allylated-gelatin (GelAGE) and Thiolated Heparin (HepSH) constructs with tailorable matrix stiffness and customized architectures. This involves systematically studying how the native glycosaminoglycan Heparin together with hydrogel stiffness, and oxygen availability within 3D structures influence chondrogenic differentiation and regional heterogeneity. A comprehensive library of 3D hydrogel constructs was successfully developed, encompassing GelAGE-HepSH hydrogels with three distinct stiffness levels: 12, 55 and 121 kPa, and three unique geometries: spheres, discs, and square lattices. In soft GelAGE-HepSH hydrogels, the localization of differentiating cells was observed to be irregular, while stiff hydrogels restricted the overall secretion of ECM components. The medium-stiff hydrogels were found to be most applicable, supporting both uniform tissue formation and maintained shape fidelity. Three different 3D architectures were explored, where biofabrication of smaller GelAGE-HepSH spheres without oxygen gradients induced homogenous, hyaline cartilage tissue formation. Conversely, fabrication of larger constructs (discs and lattices) with oxygen gradients could be utilized to design heterogenous cartilage tissue models. Similarly, temporal oxygen gradients were observed to drive interconnected deposition of glycosaminoglycans (GAGs). Control samples of GelAGE without HepSH did not exhibit any notable changes in chondrogenesis as a function of stiffness, architectures, or oxygen concentrations. Overall, the incorporation of HepSH within GelAGE hydrogels was observed to serve as an amplifier for the biological effects from both stiffness and oxygen cues. In conclusion, fabrication of GelAGE-HepSH constructs designed to impose limitations on oxygen availability induce more zone-specific cartilage tissue alignment. This systematic study of matrix components, network stiffness, and oxygen levels in 3D biofabricated structures contributes to the development of more physiologically relevant cartilage models while further enhancing our overall understanding of cartilage tissue engineering.
{"title":"Fabrication of gelatin-heparin based cartilage models: enhancing spatial complexity through refinement of stiffness properties and oxygen availability","authors":"G. Lindberg, A. Norberg, B. Soliman, T. Jüngst, K. Lim, G. Hooper, J. Groll, T. Woodfield","doi":"10.3389/fbiom.2024.1331032","DOIUrl":"https://doi.org/10.3389/fbiom.2024.1331032","url":null,"abstract":"The intricate nature of native cartilage, characterized by zonal variations in oxygen levels and ECM composition, poses a challenge for existing hydrogel-based tissue models. Consequently, these 3D models often present simplified renditions of the native tissue, failing to fully capture its heterogenous nature. The combined effects of hydrogel components, network properties, and structural designs on cellular responses are often overlooked. In this work, we aim to establish more physiological cartilage models through biofabrication of photopolymerizable allylated-gelatin (GelAGE) and Thiolated Heparin (HepSH) constructs with tailorable matrix stiffness and customized architectures. This involves systematically studying how the native glycosaminoglycan Heparin together with hydrogel stiffness, and oxygen availability within 3D structures influence chondrogenic differentiation and regional heterogeneity. A comprehensive library of 3D hydrogel constructs was successfully developed, encompassing GelAGE-HepSH hydrogels with three distinct stiffness levels: 12, 55 and 121 kPa, and three unique geometries: spheres, discs, and square lattices. In soft GelAGE-HepSH hydrogels, the localization of differentiating cells was observed to be irregular, while stiff hydrogels restricted the overall secretion of ECM components. The medium-stiff hydrogels were found to be most applicable, supporting both uniform tissue formation and maintained shape fidelity. Three different 3D architectures were explored, where biofabrication of smaller GelAGE-HepSH spheres without oxygen gradients induced homogenous, hyaline cartilage tissue formation. Conversely, fabrication of larger constructs (discs and lattices) with oxygen gradients could be utilized to design heterogenous cartilage tissue models. Similarly, temporal oxygen gradients were observed to drive interconnected deposition of glycosaminoglycans (GAGs). Control samples of GelAGE without HepSH did not exhibit any notable changes in chondrogenesis as a function of stiffness, architectures, or oxygen concentrations. Overall, the incorporation of HepSH within GelAGE hydrogels was observed to serve as an amplifier for the biological effects from both stiffness and oxygen cues. In conclusion, fabrication of GelAGE-HepSH constructs designed to impose limitations on oxygen availability induce more zone-specific cartilage tissue alignment. This systematic study of matrix components, network stiffness, and oxygen levels in 3D biofabricated structures contributes to the development of more physiologically relevant cartilage models while further enhancing our overall understanding of cartilage tissue engineering.","PeriodicalId":73067,"journal":{"name":"Frontiers in biomaterials science","volume":"43 29","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139798296","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 : 2024-02-06DOI: 10.3389/fbiom.2024.1331032
G. Lindberg, A. Norberg, B. Soliman, T. Jüngst, K. Lim, G. Hooper, J. Groll, T. Woodfield
The intricate nature of native cartilage, characterized by zonal variations in oxygen levels and ECM composition, poses a challenge for existing hydrogel-based tissue models. Consequently, these 3D models often present simplified renditions of the native tissue, failing to fully capture its heterogenous nature. The combined effects of hydrogel components, network properties, and structural designs on cellular responses are often overlooked. In this work, we aim to establish more physiological cartilage models through biofabrication of photopolymerizable allylated-gelatin (GelAGE) and Thiolated Heparin (HepSH) constructs with tailorable matrix stiffness and customized architectures. This involves systematically studying how the native glycosaminoglycan Heparin together with hydrogel stiffness, and oxygen availability within 3D structures influence chondrogenic differentiation and regional heterogeneity. A comprehensive library of 3D hydrogel constructs was successfully developed, encompassing GelAGE-HepSH hydrogels with three distinct stiffness levels: 12, 55 and 121 kPa, and three unique geometries: spheres, discs, and square lattices. In soft GelAGE-HepSH hydrogels, the localization of differentiating cells was observed to be irregular, while stiff hydrogels restricted the overall secretion of ECM components. The medium-stiff hydrogels were found to be most applicable, supporting both uniform tissue formation and maintained shape fidelity. Three different 3D architectures were explored, where biofabrication of smaller GelAGE-HepSH spheres without oxygen gradients induced homogenous, hyaline cartilage tissue formation. Conversely, fabrication of larger constructs (discs and lattices) with oxygen gradients could be utilized to design heterogenous cartilage tissue models. Similarly, temporal oxygen gradients were observed to drive interconnected deposition of glycosaminoglycans (GAGs). Control samples of GelAGE without HepSH did not exhibit any notable changes in chondrogenesis as a function of stiffness, architectures, or oxygen concentrations. Overall, the incorporation of HepSH within GelAGE hydrogels was observed to serve as an amplifier for the biological effects from both stiffness and oxygen cues. In conclusion, fabrication of GelAGE-HepSH constructs designed to impose limitations on oxygen availability induce more zone-specific cartilage tissue alignment. This systematic study of matrix components, network stiffness, and oxygen levels in 3D biofabricated structures contributes to the development of more physiologically relevant cartilage models while further enhancing our overall understanding of cartilage tissue engineering.
{"title":"Fabrication of gelatin-heparin based cartilage models: enhancing spatial complexity through refinement of stiffness properties and oxygen availability","authors":"G. Lindberg, A. Norberg, B. Soliman, T. Jüngst, K. Lim, G. Hooper, J. Groll, T. Woodfield","doi":"10.3389/fbiom.2024.1331032","DOIUrl":"https://doi.org/10.3389/fbiom.2024.1331032","url":null,"abstract":"The intricate nature of native cartilage, characterized by zonal variations in oxygen levels and ECM composition, poses a challenge for existing hydrogel-based tissue models. Consequently, these 3D models often present simplified renditions of the native tissue, failing to fully capture its heterogenous nature. The combined effects of hydrogel components, network properties, and structural designs on cellular responses are often overlooked. In this work, we aim to establish more physiological cartilage models through biofabrication of photopolymerizable allylated-gelatin (GelAGE) and Thiolated Heparin (HepSH) constructs with tailorable matrix stiffness and customized architectures. This involves systematically studying how the native glycosaminoglycan Heparin together with hydrogel stiffness, and oxygen availability within 3D structures influence chondrogenic differentiation and regional heterogeneity. A comprehensive library of 3D hydrogel constructs was successfully developed, encompassing GelAGE-HepSH hydrogels with three distinct stiffness levels: 12, 55 and 121 kPa, and three unique geometries: spheres, discs, and square lattices. In soft GelAGE-HepSH hydrogels, the localization of differentiating cells was observed to be irregular, while stiff hydrogels restricted the overall secretion of ECM components. The medium-stiff hydrogels were found to be most applicable, supporting both uniform tissue formation and maintained shape fidelity. Three different 3D architectures were explored, where biofabrication of smaller GelAGE-HepSH spheres without oxygen gradients induced homogenous, hyaline cartilage tissue formation. Conversely, fabrication of larger constructs (discs and lattices) with oxygen gradients could be utilized to design heterogenous cartilage tissue models. Similarly, temporal oxygen gradients were observed to drive interconnected deposition of glycosaminoglycans (GAGs). Control samples of GelAGE without HepSH did not exhibit any notable changes in chondrogenesis as a function of stiffness, architectures, or oxygen concentrations. Overall, the incorporation of HepSH within GelAGE hydrogels was observed to serve as an amplifier for the biological effects from both stiffness and oxygen cues. In conclusion, fabrication of GelAGE-HepSH constructs designed to impose limitations on oxygen availability induce more zone-specific cartilage tissue alignment. This systematic study of matrix components, network stiffness, and oxygen levels in 3D biofabricated structures contributes to the development of more physiologically relevant cartilage models while further enhancing our overall understanding of cartilage tissue engineering.","PeriodicalId":73067,"journal":{"name":"Frontiers in biomaterials science","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139858235","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}