Pub Date : 2024-10-01DOI: 10.1016/j.actbio.2024.08.019
Stephan Ritzert , Annabell Rjosk , Hagen Holthusen , Thea Lautenschläger , Christoph Neinhuis , Stefanie Reese
Plant leaves have to deal with various environmental influences. While the mechanical properties of petiole and lamina are generally well studied, only few studies focused on the properties of the transition zone joining petiole and lamina. Especially in peltate leaves, characterised by the attachment of the petiole to the abaxial side of the lamina, the 3D leaf architecture imposes specific mechanical stresses on the petiole and petiole-lamina transition zone. Several principles of internal anatomical organisation have been identified. Since the mechanical characterisation of the transition zone by direct measurements is difficult, we explored the mechanical properties and load-bearing mechanisms by finite-element simulations. We simulate the petiole-lamina transition zone with five different fibre models that were abstracted from CT data. For comparison, three different load cases were defined and tested in the simulation. In the proposed model, the fibres are represented in a smeared sense, where we considered transverse isotropic behavior in elements containing fibres. In a pre-processing step, we determined the fibre content, direction, and dispersion and fed them into our model. The simulations show that initially, matrix and fibres carry the load together. After relaxation of the stresses in the matrix, the fibres carry most of the load. Load dissipation and stiffness differ according to fibre arrangement and depend, among other things, on orientation and cross-linking of the fibres and fibre amount. Even though the presented method is a simplified approach, it is able to show the different load-bearing capacities of the presented fibre arrangements.
Statement of significance
In plant leaves, the petiole-lamina transition zone is an important structural element facilitating water and nutrient transport, as well as load dissipation from the lamina into the petiole. Especially in peltate leaves, the 3D leaf architecture imposes specific mechanical stresses on the petiole-lamina transition zone. This study aims at investigating its mechanical behavior using finite-element simulations. The proposed continuum mechanical anisotropic viscoelastic material model is able to simulate the transition zone under different loads while also considering different fibre arrangements. The simulations highlight the load-bearing mechanisms of different fibre organisations, show the mechanical significance of the petiole-lamina transition zone and can be used in the design of a future biomimetic junction in construction.
{"title":"Mechanical modeling of the petiole-lamina transition zone of peltate leaves","authors":"Stephan Ritzert , Annabell Rjosk , Hagen Holthusen , Thea Lautenschläger , Christoph Neinhuis , Stefanie Reese","doi":"10.1016/j.actbio.2024.08.019","DOIUrl":"10.1016/j.actbio.2024.08.019","url":null,"abstract":"<div><div>Plant leaves have to deal with various environmental influences. While the mechanical properties of petiole and lamina are generally well studied, only few studies focused on the properties of the transition zone joining petiole and lamina. Especially in peltate leaves, characterised by the attachment of the petiole to the abaxial side of the lamina, the 3D leaf architecture imposes specific mechanical stresses on the petiole and petiole-lamina transition zone. Several principles of internal anatomical organisation have been identified. Since the mechanical characterisation of the transition zone by direct measurements is difficult, we explored the mechanical properties and load-bearing mechanisms by finite-element simulations. We simulate the petiole-lamina transition zone with five different fibre models that were abstracted from CT data. For comparison, three different load cases were defined and tested in the simulation. In the proposed model, the fibres are represented in a smeared sense, where we considered transverse isotropic behavior in elements containing fibres. In a pre-processing step, we determined the fibre content, direction, and dispersion and fed them into our model. The simulations show that initially, matrix and fibres carry the load together. After relaxation of the stresses in the matrix, the fibres carry most of the load. Load dissipation and stiffness differ according to fibre arrangement and depend, among other things, on orientation and cross-linking of the fibres and fibre amount. Even though the presented method is a simplified approach, it is able to show the different load-bearing capacities of the presented fibre arrangements.</div></div><div><h3>Statement of significance</h3><div>In plant leaves, the petiole-lamina transition zone is an important structural element facilitating water and nutrient transport, as well as load dissipation from the lamina into the petiole. Especially in peltate leaves, the 3D leaf architecture imposes specific mechanical stresses on the petiole-lamina transition zone. This study aims at investigating its mechanical behavior using finite-element simulations. The proposed continuum mechanical anisotropic viscoelastic material model is able to simulate the transition zone under different loads while also considering different fibre arrangements. The simulations highlight the load-bearing mechanisms of different fibre organisations, show the mechanical significance of the petiole-lamina transition zone and can be used in the design of a future biomimetic junction in construction.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"187 ","pages":"Pages 278-290"},"PeriodicalIF":9.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142037976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1016/j.actbio.2024.08.028
Nicolás Laita , Alejandro Aparici-Gil , Aida Oliván-Viguera , Alba Pérez-Martínez , Miguel Ángel Martínez , Manuel Doblaré , Estefanía Peña
This work provides a comprehensive characterization of porcine myocardial tissue, combining true biaxial (TBx), simple triaxial shear (STS) and confined compression (CC) tests to analyze its elastic behavior under cyclic loads. We expanded this study to different zones of the ventricular free wall, providing insights into the local behavior along the longitudinal and radial coordinates. The aging impact was also assessed by comparing two age groups (4 and 8 months). Resulting data showed that the myocardium exhibits a highly nonlinear hyperelastic and incompressible behavior. We observed an anisotropy ratio of 2-2.4 between averaged peak stresses in TBx tests and 1-0.59-0.40 orthotropy ratios for normalised fiber-sheet-normal peak stresses in STS tests. We obtained a highly incompressible response, reaching volumetric pressures of 2-7 MPa for perfused tissue in CC tests, with notable differences when fluid drainage was allowed, suggesting a high permeability. Regional analysis showed reduced stiffness and anisotropy (20-25%) at the apical region compared to the medial, which we attributed to differences in the fiber field dispersion. Compressibility also increased towards the epicardium and apical regions. Regarding age-related variations, 8-month animals showed stiffer response (at least 25% increase), particularly in directions where the mechanical stress is absorbed by collagenous fibers (more than 90%), as supported by a histological analysis. Although compressibility of perfused tissue remained unchanged, permeability significantly reduced in 8-month-old animals. Our findings offer new insights into myocardial properties, emphasizing on local variations, which can help to get a more realistic understanding of cardiac mechanics in this common animal model.
Statement of significance
In this work, we conducted a comprehensive analysis of the passive mechanical behavior of porcine myocardial tissue through biaxial, triaxial shear, and confined compression tests. Unlike previous research, we investigated the variation in mechanical response across the left ventricular free wall, conventionally assumed homogeneous, revealing differences in terms of stiffness and compressibility. Additionally, we evaluated age-related effects on mechanical properties by comparing two age groups, observing significant variations in stiffness and permeability. To date, there has been no such in-depth exploration of myocardial elastic response and compressibility considering regional variations along the wall and may contribute to a better understanding of the cardiac tissue’s passive mechanical response.
{"title":"A comprehensive experimental analysis of the local passive response across the healthy porcine left ventricle","authors":"Nicolás Laita , Alejandro Aparici-Gil , Aida Oliván-Viguera , Alba Pérez-Martínez , Miguel Ángel Martínez , Manuel Doblaré , Estefanía Peña","doi":"10.1016/j.actbio.2024.08.028","DOIUrl":"10.1016/j.actbio.2024.08.028","url":null,"abstract":"<div><div>This work provides a comprehensive characterization of porcine myocardial tissue, combining true biaxial (TBx), simple triaxial shear (STS) and confined compression (CC) tests to analyze its elastic behavior under cyclic loads. We expanded this study to different zones of the ventricular free wall, providing insights into the local behavior along the longitudinal and radial coordinates. The aging impact was also assessed by comparing two age groups (4 and 8 months). Resulting data showed that the myocardium exhibits a highly nonlinear hyperelastic and incompressible behavior. We observed an anisotropy ratio of 2-2.4 between averaged peak stresses in TBx tests and 1-0.59-0.40 orthotropy ratios for normalised fiber-sheet-normal peak stresses in STS tests. We obtained a highly incompressible response, reaching volumetric pressures of 2-7 MPa for perfused tissue in CC tests, with notable differences when fluid drainage was allowed, suggesting a high permeability. Regional analysis showed reduced stiffness and anisotropy (20-25%) at the apical region compared to the medial, which we attributed to differences in the fiber field dispersion. Compressibility also increased towards the epicardium and apical regions. Regarding age-related variations, 8-month animals showed stiffer response (at least 25% increase), particularly in directions where the mechanical stress is absorbed by collagenous fibers (more than 90%), as supported by a histological analysis. Although compressibility of perfused tissue remained unchanged, permeability significantly reduced in 8-month-old animals. Our findings offer new insights into myocardial properties, emphasizing on local variations, which can help to get a more realistic understanding of cardiac mechanics in this common animal model.</div></div><div><h3>Statement of significance</h3><div>In this work, we conducted a comprehensive analysis of the passive mechanical behavior of porcine myocardial tissue through biaxial, triaxial shear, and confined compression tests. Unlike previous research, we investigated the variation in mechanical response across the left ventricular free wall, conventionally assumed homogeneous, revealing differences in terms of stiffness and compressibility. Additionally, we evaluated age-related effects on mechanical properties by comparing two age groups, observing significant variations in stiffness and permeability. To date, there has been no such in-depth exploration of myocardial elastic response and compressibility considering regional variations along the wall and may contribute to a better understanding of the cardiac tissue’s passive mechanical response.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"187 ","pages":"Pages 261-277"},"PeriodicalIF":9.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142074748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<div><div>The present study adopts a multi-facet approach to design bio inspired concentrated alloys for potential application as articulating surfaces in joint replacements. A series of equiatomic, Nb rich and Ti rich TiMoNbZr based medium entropy alloys (MEAs) were processed via arc melting and their mechanical, <em>in-vitro</em> corrosion, wear, and <em>in vitro</em> and <em>in vivo</em> biocompatibility were investigated. Equiatomic MEA had primarily bcc with minor hcp phases where the single bcc was achieved with the addition of Nb. The single bcc Nb rich alloy resulted in 13 % elongation, much higher than equiatomic or Ti rich alloy. All the MEAs showed comparatively higher yield strength due to the climb of edge dislocations which is the main rate limiting mechanism at 300 K, as evident molecular dynamics (MD) simulation. The locally fluctuating energy landscape promotes kinks on edge dislocation, and at local minima nanoscale segments gets pinned. Upon yielding the entangled kink leaves a trail of vacancies/interstitials and escapes via climb motion to render high yield strength. The higher corrosion and pitting resistance of Nb enriched alloys can be attributed to the stable ZrO<sub>2</sub>, Nb<sub>2</sub>O<sub>5</sub>, TiO<sub>2</sub>, and MoO<sub>3</sub> oxides, high polarization resistance (10<sup>6</sup>–10<sup>5</sup> Ωcm<sup>−2</sup>), and low defect densities (10<sup>16</sup>–10<sup>18</sup>). <em>In vitro</em> cell-materials interaction using MC3T3-E1 showed bioinert but cytocompatible nature of the MEAs. The wear rate of the MEAs was in the range of 7–9 × 10<sup>−5</sup> mm<sup>3</sup>N<sup>−1</sup>m<sup>−1</sup>. The wear debris did not show any tissue necrosis when implanted in rabbit femur rather new bone regeneration can be seen around the particles.</div></div><div><h3>Statement of significance</h3><div>In the present work, a noble Nb enriched MEAs with superior mechanical, <em>in vitro</em> wear, corrosion and cytocompatibility properties was designed for articulating surfaces in joint replacement.<ul><li><span>•</span><span><div>Single bcc in Nb enriched MEAs resulted in 13 % elongation with high hardness and yield strength.</div></span></li><li><span>•</span><span><div>Climb of entangled edge segment is the rate limiting mechanism in controlling high yield strength of MEAs at 300 K.</div></span></li><li><span>•</span><span><div>High polarization resistance (10<sup>6</sup>–10<sup>5</sup> Ωcm<sup>−2</sup>), and low defect densities (10<sup>16</sup>–10<sup>18</sup>) attributes to ZrO<sub>2</sub>, Nb<sub>2</sub>O<sub>5</sub>, TiO<sub>2</sub>, and MoO<sub>3</sub> oxides enriched passive film.</div></span></li><li><span>•</span><span><div>Wet sliding wear rate ranged in order 7–9 × 10<sup>−5</sup> mm<sup>3</sup>N<sup>−1</sup>m<sup>−1</sup>. <em>In-situ</em> generated wear debris when implanted in rabbit femur did not show any tissue necrosis rather new bone regeneration was observed around debris.</div></span></li></ul></div><
本研究采用一种多面方法来设计受生物启发的浓缩合金，以便将其用作关节置换的关节面。研究人员通过电弧熔化法加工了一系列等原子、富铌和富钛的 TiMoNbZr 基中熵合金 (MEA)，并对其机械性能、体外腐蚀、磨损、体外和体内生物相容性进行了研究。等原子 MEA 主要具有 bcc 相和少量 hcp 相，其中单一 bcc 相是通过添加铌实现的。单一 bcc 富铌合金的伸长率为 13%，远高于等原子或富钛合金。分子动力学（MD）模拟显示，由于边缘位错的攀升，所有 MEA 的屈服强度都相对较高，而边缘位错攀升是 300 K 时的主要速率限制机制。局部波动的能量分布促进了边缘位错的扭结，在局部最小值处，纳米级的区段被钉住。屈服时，缠结的扭结会留下空位/间隙的痕迹，并通过爬升运动逃逸，从而产生较高的屈服强度。富含铌的合金具有更高的耐腐蚀性和抗点蚀性，这要归功于稳定的 ZrO2、Nb2O5、TiO2 和 MoO3 氧化物、高极化电阻（106-105 Ωcm-2）和低缺陷密度（1016-1018）。使用 MC3T3-E1 进行的体外细胞-材料相互作用表明，MEAs 具有生物惰性和细胞相容性。MEA 的磨损率在 7-9×10-5 mm3N-1m-1 之间。将磨损碎片植入兔子股骨后，未发现任何组织坏死，反而可以看到颗粒周围有新的骨再生。意义说明：在本研究中，我们设计了一种具有优异机械性能、体外磨损性能、腐蚀性能和细胞相容性能的高贵铌富集 MEAs，用于关节置换中的关节表面。-富含铌的 MEAs 中的单一铍可产生 13% 的伸长率，并具有较高的硬度和屈服强度。-缠结边段的爬升是控制 300 K 时 MEA 高屈服强度的速率限制机制。-高极化电阻（106-105 Ωcm-2）和低缺陷密度（1016-1018）归因于富含 ZrO2、Nb2O5、TiO2 和 MoO3 氧化物的被动薄膜。-湿滑动磨损率约为 7-9×10-5 mm3N-1m-1。将原位生成的磨损碎片植入兔子股骨后，未发现任何组织坏死，反而观察到碎片周围有新的骨再生。
{"title":"Functional medium entropy alloys for joint replacement: An atomistic perspective of material deformation and a correlation to wear, corrosion, and biocompatibility","authors":"Avinash Chavan , Indu Avula , Satyabrata Nigamananda Sahoo , Sankalp Biswal , Santanu Mandal , Madud Musthafa , Subhasis Roy , Samit Kumar Nandi , Sankha Mukherjee , Mangal Roy","doi":"10.1016/j.actbio.2024.08.031","DOIUrl":"10.1016/j.actbio.2024.08.031","url":null,"abstract":"<div><div>The present study adopts a multi-facet approach to design bio inspired concentrated alloys for potential application as articulating surfaces in joint replacements. A series of equiatomic, Nb rich and Ti rich TiMoNbZr based medium entropy alloys (MEAs) were processed via arc melting and their mechanical, <em>in-vitro</em> corrosion, wear, and <em>in vitro</em> and <em>in vivo</em> biocompatibility were investigated. Equiatomic MEA had primarily bcc with minor hcp phases where the single bcc was achieved with the addition of Nb. The single bcc Nb rich alloy resulted in 13 % elongation, much higher than equiatomic or Ti rich alloy. All the MEAs showed comparatively higher yield strength due to the climb of edge dislocations which is the main rate limiting mechanism at 300 K, as evident molecular dynamics (MD) simulation. The locally fluctuating energy landscape promotes kinks on edge dislocation, and at local minima nanoscale segments gets pinned. Upon yielding the entangled kink leaves a trail of vacancies/interstitials and escapes via climb motion to render high yield strength. The higher corrosion and pitting resistance of Nb enriched alloys can be attributed to the stable ZrO<sub>2</sub>, Nb<sub>2</sub>O<sub>5</sub>, TiO<sub>2</sub>, and MoO<sub>3</sub> oxides, high polarization resistance (10<sup>6</sup>–10<sup>5</sup> Ωcm<sup>−2</sup>), and low defect densities (10<sup>16</sup>–10<sup>18</sup>). <em>In vitro</em> cell-materials interaction using MC3T3-E1 showed bioinert but cytocompatible nature of the MEAs. The wear rate of the MEAs was in the range of 7–9 × 10<sup>−5</sup> mm<sup>3</sup>N<sup>−1</sup>m<sup>−1</sup>. The wear debris did not show any tissue necrosis when implanted in rabbit femur rather new bone regeneration can be seen around the particles.</div></div><div><h3>Statement of significance</h3><div>In the present work, a noble Nb enriched MEAs with superior mechanical, <em>in vitro</em> wear, corrosion and cytocompatibility properties was designed for articulating surfaces in joint replacement.<ul><li><span>•</span><span><div>Single bcc in Nb enriched MEAs resulted in 13 % elongation with high hardness and yield strength.</div></span></li><li><span>•</span><span><div>Climb of entangled edge segment is the rate limiting mechanism in controlling high yield strength of MEAs at 300 K.</div></span></li><li><span>•</span><span><div>High polarization resistance (10<sup>6</sup>–10<sup>5</sup> Ωcm<sup>−2</sup>), and low defect densities (10<sup>16</sup>–10<sup>18</sup>) attributes to ZrO<sub>2</sub>, Nb<sub>2</sub>O<sub>5</sub>, TiO<sub>2</sub>, and MoO<sub>3</sub> oxides enriched passive film.</div></span></li><li><span>•</span><span><div>Wet sliding wear rate ranged in order 7–9 × 10<sup>−5</sup> mm<sup>3</sup>N<sup>−1</sup>m<sup>−1</sup>. <em>In-situ</em> generated wear debris when implanted in rabbit femur did not show any tissue necrosis rather new bone regeneration was observed around debris.</div></span></li></ul></div><","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"187 ","pages":"Pages 451-470"},"PeriodicalIF":9.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142074749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1016/j.actbio.2024.08.040
Iris G. Mercer , Karen Yu , Alexander J. Devanny , Melissa B. Gordon , Laura J. Kaufman
The extracellular matrix protein collagen I has been used extensively in the field of biomaterials due to its inherent biocompatibility and unique viscoelastic and mechanical properties. Collagen I self-assembly into fibers and networks is environmentally sensitive to gelation conditions such as temperature, resulting in gels with distinct network architectures and mechanical properties. Despite this, collagen gels are not suitable for many applications given their relatively low storage modulus. We have prepared collagen-poly(ethylene glycol) [PEG] interpenetrating network (IPN) hydrogels to reinforce the collagen network, which also induces changes to network plasticity, a recent focus of study in cell-matrix interactions. Here, we prepare collagen/PEG IPNs, varying collagen concentration and collagen gelation temperature to assess changes in microarchitecture and mechanical properties of these networks. By tuning these parameters, IPNs with a range of stiffness, plasticity and pore size are obtained. Cell studies suggest that matrix plasticity is a key determinant of cell behavior, including cell elongation, on these gels. This work presents a natural/synthetic biocompatible matrix that retains the unique structural properties of collagen networks with increased storage modulus and tunable plasticity. The described IPN materials will be of use for applications in which control of cell spreading is desirable, as only minimal changes in sample preparation lead to changes in cell spreading and circularity. Additionally, this study contributes to our understanding of the connection between collagen self-assembly conditions and matrix structural and mechanical properties and presents them as useful tools for the design of other collagen based biomaterials.
Statement of significance
We developed a collagen-poly(ethylene glycol) interpenetrating network (IPN) platform that retains native collagen architecture and biocompatibility but provides higher stiffness and tunable plasticity. With minor changes in collagen gelation temperature or concentration, IPN gels with a range of plasticity, storage modulus, and pore size can be obtained. The tunable plasticity of the gels is shown to modulate cell spreading, with a greater proportion of elongated cells on the most plastic of IPNs, supporting the assertion that matrix plasticity is a key determinant of cell spreading. The material can be of use for situations where control of cell spreading is desired with minimal intervention, and the findings herein may be used to develop similar collagen based IPN platforms.
细胞外基质蛋白质胶原蛋白 I 因其固有的生物相容性和独特的粘弹性及机械特性，已被广泛应用于生物材料领域。胶原蛋白 I 自组装成纤维和网络对温度等凝胶化条件的环境敏感，从而形成具有独特网络结构和机械性能的凝胶。尽管如此，由于胶原蛋白凝胶的储存模量相对较低，因此并不适用于许多应用领域。我们制备了胶原蛋白-聚乙二醇（PEG）互穿网络（IPN）水凝胶来增强胶原蛋白网络，这也诱导了网络可塑性的变化，这是细胞-基质相互作用的最新研究重点。在此，我们制备了不同胶原浓度和胶原凝胶化温度的胶原/PEG IPN，以评估这些网络的微观结构和机械性能的变化。通过调整这些参数，可获得具有不同硬度、可塑性和孔径的 IPN。细胞研究表明，基质可塑性是决定细胞在这些凝胶上的行为（包括细胞伸长）的关键因素。这项研究提出了一种天然/合成的生物相容性基质，它保留了胶原蛋白网络的独特结构特性，并增加了储存模量和可调塑性。所描述的 IPN 材料将用于需要控制细胞铺展的应用中，因为样品制备中的微小变化就会导致细胞铺展和圆度的变化。此外，这项研究还有助于我们理解胶原蛋白自组装条件与基质结构和机械性能之间的联系，并将其作为设计其他基于胶原蛋白的生物材料的有用工具。意义说明：我们开发了一种胶原蛋白-聚乙二醇互穿网络（IPN）平台，它保留了原生胶原蛋白的结构和生物相容性，但具有更高的硬度和可调可塑性。只需稍稍改变胶原蛋白的凝胶化温度或浓度，就能获得具有不同可塑性、储存模量和孔径的 IPN 凝胶。研究表明，凝胶的可调可塑性可调节细胞的扩散，在可塑性最强的 IPN 上，伸长细胞的比例更大，这支持了基质可塑性是细胞扩散的关键决定因素这一观点。这种材料可用于需要以最小干预控制细胞扩散的情况，本文的研究结果可用于开发类似的基于胶原蛋白的 IPN 平台。
{"title":"Plasticity variable collagen-PEG interpenetrating networks modulate cell spreading","authors":"Iris G. Mercer , Karen Yu , Alexander J. Devanny , Melissa B. Gordon , Laura J. Kaufman","doi":"10.1016/j.actbio.2024.08.040","DOIUrl":"10.1016/j.actbio.2024.08.040","url":null,"abstract":"<div><div>The extracellular matrix protein collagen I has been used extensively in the field of biomaterials due to its inherent biocompatibility and unique viscoelastic and mechanical properties. Collagen I self-assembly into fibers and networks is environmentally sensitive to gelation conditions such as temperature, resulting in gels with distinct network architectures and mechanical properties. Despite this, collagen gels are not suitable for many applications given their relatively low storage modulus. We have prepared collagen-poly(ethylene glycol) [PEG] interpenetrating network (IPN) hydrogels to reinforce the collagen network, which also induces changes to network plasticity, a recent focus of study in cell-matrix interactions. Here, we prepare collagen/PEG IPNs, varying collagen concentration and collagen gelation temperature to assess changes in microarchitecture and mechanical properties of these networks. By tuning these parameters, IPNs with a range of stiffness, plasticity and pore size are obtained. Cell studies suggest that matrix plasticity is a key determinant of cell behavior, including cell elongation, on these gels. This work presents a natural/synthetic biocompatible matrix that retains the unique structural properties of collagen networks with increased storage modulus and tunable plasticity. The described IPN materials will be of use for applications in which control of cell spreading is desirable, as only minimal changes in sample preparation lead to changes in cell spreading and circularity. Additionally, this study contributes to our understanding of the connection between collagen self-assembly conditions and matrix structural and mechanical properties and presents them as useful tools for the design of other collagen based biomaterials.</div></div><div><h3>Statement of significance</h3><div>We developed a collagen-poly(ethylene glycol) interpenetrating network (IPN) platform that retains native collagen architecture and biocompatibility but provides higher stiffness and tunable plasticity. With minor changes in collagen gelation temperature or concentration, IPN gels with a range of plasticity, storage modulus, and pore size can be obtained. The tunable plasticity of the gels is shown to modulate cell spreading, with a greater proportion of elongated cells on the most plastic of IPNs, supporting the assertion that matrix plasticity is a key determinant of cell spreading. The material can be of use for situations where control of cell spreading is desired with minimal intervention, and the findings herein may be used to develop similar collagen based IPN platforms.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"187 ","pages":"Pages 242-252"},"PeriodicalIF":9.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142115792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Although immunogenic cell death (ICD) induced by lysosomal membrane permeabilization (LMP) evidently enhance the effectiveness of antitumor immunity for triple-negative breast cancer (TNBC) with poor immunogenicity, their potential is increasingly restricted by the development of other death pathways and the repair of lysosomes by endoplasmic reticulum (ER) during LMP induction. Herein, a polydopamine nanocomposite with i-motif DNA modified and BNN6 loaded is prepared toward boosting LMP and immunotherapy of TNBC by synergy of spatially confined photoacoustic (PA) effects and nitric oxide. Combining the high-frequency pulsed laser (4000 kHz) with the intra-lysosomal assembly of nanocomposites produced spatially confined and significantly boosted PA effects (4.8-fold higher than the individually dispersed particles extracellular), suppressing damage to other cellular components and selectively reducing lysosomal integrity to 19.2 %. Simultaneously, the releasing of nitric oxide inhibited the repair of lysosomes by ER stress, causing exacerbated LMP. Consequently, efficient immune activation was achieved, including the abundant releasing of CRT/HMGB1 (5.93–6.8-fold), the increasing maturation of dendritic cells (3.41-fold), and the fostered recruitment of CD4+/CD8+T cells (3.99–3.78-fold) in vivo. The study paves a new avenue for the rational design and synergy of confined energy conversion and responsive nanostructures to achieve the treatment of low immunogenicity tumors.
Statement of significance
A strategy of boosting lysosomal membrane permeabilization (LMP) and concomitantly preventing the repair was developed to address the immunotherapy challenge of triple-negative breast cancer. Spatially confined and significantly enhanced photoacoustic (PA) effects were achieved through DNA-guided pH-responsive assembly of polydopamine nanocomposites in lysosomes and application of a high-frequency pulsed laser. Efficient immunogenic cell death was guaranteed by selective and powerful damage of lysosomal membranes through the significant contrast of PA intensities for dispersed/assembled particles and nitric oxide release induced endoplasmic reticulum stress. The study paves a new avenue for the rational design and synergy of confined energy conversion and responsive nanostructures to achieve the treatment of low immunogenicity tumors.
尽管溶酶体膜通透性（LMP）诱导的免疫原性细胞死亡（ICD）能明显提高免疫原性较差的三阴性乳腺癌（TNBC）的抗肿瘤免疫效果，但由于其他死亡途径的发展以及LMP诱导过程中内质网（ER）对溶酶体的修复，其潜力正日益受到限制。本文制备了一种修饰了i-motif DNA并负载了BNN6的聚多巴胺纳米复合材料，通过空间约束光声（PA）效应和一氧化氮的协同作用，促进LMP和TNBC的免疫治疗。将高频脉冲激光（4000 kHz）与纳米复合材料在溶酶体内的组装相结合，产生了空间致密且显著增强的光声效应（比单独分散在细胞外的颗粒高出4.8倍），抑制了对其他细胞成分的损伤，并选择性地将溶酶体完整性降低至19.2%。同时，一氧化氮的释放抑制了ER应激对溶酶体的修复，导致LMP加剧。因此，在体内实现了高效的免疫激活，包括大量释放 CRT/HMGB1（5.93-6.8 倍）、提高树突状细胞的成熟度（3.41 倍）以及促进 CD4+/CD8+ T 细胞的招募（3.99-3.78 倍）。这项研究为合理设计和协同利用封闭能量转换和响应性纳米结构治疗低免疫原性肿瘤开辟了一条新途径。意义说明：为应对三阴性乳腺癌的免疫疗法挑战，我们开发了一种提高溶酶体膜通透性（LMP）并同时防止修复的策略。通过 DNA 引导的溶酶体中多多巴胺纳米复合材料的 pH 响应组装以及高频脉冲激光的应用，实现了空间限制和显著增强的光声（PA）效应。通过分散/组装颗粒的 PA 强度与一氧化氮释放诱导的内质网应激的显著对比，对溶酶体膜造成了选择性的强力破坏，从而保证了高效的免疫性细胞死亡。这项研究为合理设计和协同利用封闭能量转换和响应性纳米结构治疗低免疫原性肿瘤开辟了一条新途径。
{"title":"Spatially confined photoacoustic effects of responsive nanoassembly boosts lysosomal membrane permeabilization and immunotherapy of triple-negative breast cancer","authors":"Kunlin Li, Lin Li, Xiyue Xie, Jing Zhu, Daqing Xia, Lunli Xiang, Kaiyong Cai, Jixi Zhang","doi":"10.1016/j.actbio.2024.08.021","DOIUrl":"10.1016/j.actbio.2024.08.021","url":null,"abstract":"<div><div>Although immunogenic cell death (ICD) induced by lysosomal membrane permeabilization (LMP) evidently enhance the effectiveness of antitumor immunity for triple-negative breast cancer (TNBC) with poor immunogenicity, their potential is increasingly restricted by the development of other death pathways and the repair of lysosomes by endoplasmic reticulum (ER) during LMP induction. Herein, a polydopamine nanocomposite with i-motif DNA modified and BNN6 loaded is prepared toward boosting LMP and immunotherapy of TNBC by synergy of spatially confined photoacoustic (PA) effects and nitric oxide. Combining the high-frequency pulsed laser (4000 kHz) with the intra-lysosomal assembly of nanocomposites produced spatially confined and significantly boosted PA effects (4.8-fold higher than the individually dispersed particles extracellular), suppressing damage to other cellular components and selectively reducing lysosomal integrity to 19.2 %. Simultaneously, the releasing of nitric oxide inhibited the repair of lysosomes by ER stress, causing exacerbated LMP. Consequently, efficient immune activation was achieved, including the abundant releasing of CRT/HMGB1 (5.93–6.8-fold), the increasing maturation of dendritic cells (3.41-fold), and the fostered recruitment of CD4<sup>+</sup>/CD8<sup>+</sup> <em>T</em> cells (3.99–3.78-fold) <em>in vivo</em>. The study paves a new avenue for the rational design and synergy of confined energy conversion and responsive nanostructures to achieve the treatment of low immunogenicity tumors.</div></div><div><h3>Statement of significance</h3><div>A strategy of boosting lysosomal membrane permeabilization (LMP) and concomitantly preventing the repair was developed to address the immunotherapy challenge of triple-negative breast cancer. Spatially confined and significantly enhanced photoacoustic (PA) effects were achieved through DNA-guided pH-responsive assembly of polydopamine nanocomposites in lysosomes and application of a high-frequency pulsed laser. Efficient immunogenic cell death was guaranteed by selective and powerful damage of lysosomal membranes through the significant contrast of PA intensities for dispersed/assembled particles and nitric oxide release induced endoplasmic reticulum stress. The study paves a new avenue for the rational design and synergy of confined energy conversion and responsive nanostructures to achieve the treatment of low immunogenicity tumors.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"187 ","pages":"Pages 381-395"},"PeriodicalIF":9.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142115794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1016/j.actbio.2024.08.043
Yikang Xu , K. Scott Phillips , Dacheng Ren
Many medical devices implanted in patients to mitigate diseases and medical conditions have different types of topographic features. While appropriate textures can promote the integration of host cells and reduce scar tissue formation, some textured implants with inappropriate topographies have been associated with inflammation, bacterial colonization, or even malignant complications. To better understand how surface topography affects host immune response to colonizing bacteria, a protocol was developed to investigate phagocytosis of bacterial cells attached on polydimethylsiloxane (PDMS) surfaces with different square-shaped recessive patterns. The interaction between activated RAW 264.7 macrophages and Escherichia coli in recessive wells was visualized in 3D using multiple fluorescent markers. The results revealed that there is a threshold dimension of topography, below which phagocytosis of attached bacterial cells is significantly impeded. Specifically, under our experimental condition, up to 100-fold reduction in phagocytosis was observed in square-shaped patterns with 5 µm side length and 10 µm depth compared to the flat control and patterns with 10 µm or longer side length. The spacing between wells also showed significant effects; e.g., phagocytosis in the wells further decreased when spacing increased to 50 µm. These results are helpful for understanding how undesired topographies may contribute to bacterial colonization and thus infection and other associated complications.
Statement of significance
Surface topography plays an important role in bacteria-material infections and thus the safety of implantable medical devices. Undesired topographic features can cause biofilm formation and related complications. However, how surface topography affects the capability of host immune cells to clear colonizing bacteria is not well understood. In this study, the interaction between macrophage RAW264.7 and colonizing E. coli cells on polydimethylsiloxane (PDMS) with recessive features is investigated. It was discovered that the size of recessive features and the spacing between these features have significant effects on phagocytosis of bacteria by macrophages. These new results are helpful for understanding the complex interaction among host cells, bacteria, and implanted biomaterials, which will help guide the rational design of safer medical devices.
{"title":"Micron-scale topographies affect phagocytosis of bacterial cells on polydimethylsiloxane surfaces","authors":"Yikang Xu , K. Scott Phillips , Dacheng Ren","doi":"10.1016/j.actbio.2024.08.043","DOIUrl":"10.1016/j.actbio.2024.08.043","url":null,"abstract":"<div><div>Many medical devices implanted in patients to mitigate diseases and medical conditions have different types of topographic features. While appropriate textures can promote the integration of host cells and reduce scar tissue formation, some textured implants with inappropriate topographies have been associated with inflammation, bacterial colonization, or even malignant complications. To better understand how surface topography affects host immune response to colonizing bacteria, a protocol was developed to investigate phagocytosis of bacterial cells attached on polydimethylsiloxane (PDMS) surfaces with different square-shaped recessive patterns. The interaction between activated RAW 264.7 macrophages and <em>Escherichia coli</em> in recessive wells was visualized in 3D using multiple fluorescent markers. The results revealed that there is a threshold dimension of topography, below which phagocytosis of attached bacterial cells is significantly impeded. Specifically, under our experimental condition, up to 100-fold reduction in phagocytosis was observed in square-shaped patterns with 5 µm side length and 10 µm depth compared to the flat control and patterns with 10 µm or longer side length. The spacing between wells also showed significant effects; e.g., phagocytosis in the wells further decreased when spacing increased to 50 µm. These results are helpful for understanding how undesired topographies may contribute to bacterial colonization and thus infection and other associated complications.</div></div><div><h3>Statement of significance</h3><div>Surface topography plays an important role in bacteria-material infections and thus the safety of implantable medical devices. Undesired topographic features can cause biofilm formation and related complications. However, how surface topography affects the capability of host immune cells to clear colonizing bacteria is not well understood. In this study, the interaction between macrophage RAW264.7 and colonizing <em>E. coli</em> cells on polydimethylsiloxane (PDMS) with recessive features is investigated. It was discovered that the size of recessive features and the spacing between these features have significant effects on phagocytosis of bacteria by macrophages. These new results are helpful for understanding the complex interaction among host cells, bacteria, and implanted biomaterials, which will help guide the rational design of safer medical devices.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"187 ","pages":"Pages 253-260"},"PeriodicalIF":9.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142115777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1016/j.actbio.2024.08.051
Haijun Hu , Huan Gao , Kai Wang , Zeyuan Jin , Weiwei Zheng , Qiaoxuan Wang , Yufang Yang , Chaonan Yu , Kedi Xu , Changyou Gao
Traumatic brain injury (TBI) is an incurable and overwhelming disease accompanied with serve disability and huge financial burden, where the overproduced reactive oxygen species (ROS) can exacerbate the secondary injury, leading to massive apoptosis of neurons. In this study, β-cyclodextrin (CD)-capped hyperbranched polymers containing selenium element (HSE-CD) were crosslinked with CD-modified hyaluronic acid (HA-CD) and amantadine-modified hyaluronic acid (HA-AD) to obtain a ROS-responsive ointment (R-O). The structures of synthesized polymers were characterized with 1H nuclear magnetic resonance, and the properties of ointment were investigated with rheology and antioxidation. Compared to non-ROS-responsive ointment (N-O), the R-O ointment had stronger efficiency in decreasing the ROS level in BV2 cells in vitro. In a controlled rat cortical impact (CCI) model, the R-O ointment could relieve the DNA damage and decrease apoptosis in injured area via reducing the ROS level. Besides, after the R-O treatment, the rats showed significantly less activated astrocytes and microglia, a lower level of pro-inflammatory cytokines and a higher ratio of M2/M1 macrophage and microglia. Moreover, compared to the TBI group the R-O ointment promoted the doublecortin (DCX) expression and tissue structure integrity around the cavity, and promoted the recovery of nerve function post TBI.
Statement of significance
Traumatic brain injury (TBI) is an incurable and overwhelming disease, leading to severe disability and huge social burden, where reactive oxygen species (ROS) are considered as one of the most significant factors in the secondary injury of TBI. A ROS responsive supramolecular ointment containing di-selenide bonds was injected in rats with controlled cortical impact. It relieved the DNA damage and decreased apoptosis in the injured area via reducing the ROS levels, downregulated neuroinflammation, and improved neurological recovery of TBI in vivo. This designed self-adaptive biomaterial effectively regulated the pathological microenvironment in injured tissue, and achieved better therapeutic effect.
{"title":"Effective treatment of traumatic brain injury by injection of a selenium-containing ointment","authors":"Haijun Hu , Huan Gao , Kai Wang , Zeyuan Jin , Weiwei Zheng , Qiaoxuan Wang , Yufang Yang , Chaonan Yu , Kedi Xu , Changyou Gao","doi":"10.1016/j.actbio.2024.08.051","DOIUrl":"10.1016/j.actbio.2024.08.051","url":null,"abstract":"<div><div>Traumatic brain injury (TBI) is an incurable and overwhelming disease accompanied with serve disability and huge financial burden, where the overproduced reactive oxygen species (ROS) can exacerbate the secondary injury, leading to massive apoptosis of neurons. In this study, β-cyclodextrin (CD)-capped hyperbranched polymers containing selenium element (HSE-CD) were crosslinked with CD-modified hyaluronic acid (HA-CD) and amantadine-modified hyaluronic acid (HA-AD) to obtain a ROS-responsive ointment (R-O). The structures of synthesized polymers were characterized with <sup>1</sup>H nuclear magnetic resonance, and the properties of ointment were investigated with rheology and antioxidation. Compared to non-ROS-responsive ointment (N-O), the R-O ointment had stronger efficiency in decreasing the ROS level in BV2 cells <em>in vitro</em>. In a controlled rat cortical impact (CCI) model, the R-O ointment could relieve the DNA damage and decrease apoptosis in injured area via reducing the ROS level. Besides, after the R-O treatment, the rats showed significantly less activated astrocytes and microglia, a lower level of pro-inflammatory cytokines and a higher ratio of M2/M1 macrophage and microglia. Moreover, compared to the TBI group the R-O ointment promoted the doublecortin (DCX) expression and tissue structure integrity around the cavity, and promoted the recovery of nerve function post TBI.</div></div><div><h3>Statement of significance</h3><div>Traumatic brain injury (TBI) is an incurable and overwhelming disease, leading to severe disability and huge social burden, where reactive oxygen species (ROS) are considered as one of the most significant factors in the secondary injury of TBI. A ROS responsive supramolecular ointment containing di-selenide bonds was injected in rats with controlled cortical impact. It relieved the DNA damage and decreased apoptosis in the injured area via reducing the ROS levels, downregulated neuroinflammation, and improved neurological recovery of TBI <em>in vivo</em>. This designed self-adaptive biomaterial effectively regulated the pathological microenvironment in injured tissue, and achieved better therapeutic effect.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"187 ","pages":"Pages 161-171"},"PeriodicalIF":9.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142141998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1016/j.actbio.2024.08.020
Wei Gao , Xinyuan Yu , Chunpeng Zhang , Haoyang Du , Shiya Yang , Hao Wang , Jiuxin Zhu , Yakun Luo , Manjie Zhang
Balancing biocompatibility and drug-loading efficiency in nanoparticles presents a significant challenge. In this study, we describe the facile fabrication of poly (acrylic acid)-mesoporous zinc phosphate/polydopamine (PAA-mZnP/PDA) Janus nanoparticles (JNPs). The PDA half-shell itself can serve as a photothermal agent for photothermal therapy (PTT), as well as to offers sites for polyethylene glycol (PEG) to enhance biocompatibility. Concurrently, the mesoporous ZnP core allows high loading of doxorubicin (DOX) for chemotherapy and the Cy5.5 dye for fluorescence imaging. The resultant PAA-mZnP/PDA-PEG JNPs exhibit exceptional biocompatibility, efficient drug loading (0.5 mg DOX/1 mg JNPs), and dual pH/NIR-responsive drug release properties. We demonstrate the JNPs’ satisfactory anti-cancer efficacy, highlighting the synergistic effects of chemotherapy and PTT. Furthermore, the potential for synergistic fluorescence imaging-guided chemo-phototherapy in cancer treatment is illustrated. Thus, this work exemplifies the development of biosafe, multifunctional JNPs for advanced applications in cancer theranostics.
Statement of significance
Facile fabrication of monodispersed nanomedicine with multi-cancer killing modalities organically integrated is nontrivial and becomes more challenging under the biocompatibility requirement that is necessary for the practical applications of nanomedicines. In this study, we creatively designed PAA-mZnP/PDA JNPs and fabricated them under mild conditions. Our method reliably yields uniform JNPs with excellent monodispersity. To maximize functionalities, we achieve fourfold advantages including efficient drug/fluorescent dye loading, PTT, pH/NIR dual-responsive properties, and optimal biocompatibility. The as-fabricated JNPs exhibit satisfactory anti-cancer performance both in vitro and in vivo, and demonstrate the potential of JNPs in fluorescence imaging-guided synergistic cancer chemo-phototherapy. Overall, our research establishes a pathway in versatile inorganic/polymer JNPs for enhanced cancer diagnosis and therapy.
{"title":"Facile fabrications of poly (acrylic acid)-mesoporous zinc phosphate/polydopamine Janus nanoparticles as a biosafe photothermal therapy agent and a pH/NIR-responsive drug carrier","authors":"Wei Gao , Xinyuan Yu , Chunpeng Zhang , Haoyang Du , Shiya Yang , Hao Wang , Jiuxin Zhu , Yakun Luo , Manjie Zhang","doi":"10.1016/j.actbio.2024.08.020","DOIUrl":"10.1016/j.actbio.2024.08.020","url":null,"abstract":"<div><div>Balancing biocompatibility and drug-loading efficiency in nanoparticles presents a significant challenge. In this study, we describe the facile fabrication of poly (acrylic acid)-mesoporous zinc phosphate/polydopamine (PAA-mZnP/PDA) Janus nanoparticles (JNPs). The PDA half-shell itself can serve as a photothermal agent for photothermal therapy (PTT), as well as to offers sites for polyethylene glycol (PEG) to enhance biocompatibility. Concurrently, the mesoporous ZnP core allows high loading of doxorubicin (DOX) for chemotherapy and the Cy5.5 dye for fluorescence imaging. The resultant PAA-mZnP/PDA-PEG JNPs exhibit exceptional biocompatibility, efficient drug loading (0.5 mg DOX/1 mg JNPs), and dual pH/NIR-responsive drug release properties. We demonstrate the JNPs’ satisfactory anti-cancer efficacy, highlighting the synergistic effects of chemotherapy and PTT. Furthermore, the potential for synergistic fluorescence imaging-guided chemo-phototherapy in cancer treatment is illustrated. Thus, this work exemplifies the development of biosafe, multifunctional JNPs for advanced applications in cancer theranostics.</div></div><div><h3>Statement of significance</h3><div>Facile fabrication of monodispersed nanomedicine with multi-cancer killing modalities organically integrated is nontrivial and becomes more challenging under the biocompatibility requirement that is necessary for the practical applications of nanomedicines. In this study, we creatively designed PAA-mZnP/PDA JNPs and fabricated them under mild conditions. Our method reliably yields uniform JNPs with excellent monodispersity. To maximize functionalities, we achieve fourfold advantages including efficient drug/fluorescent dye loading, PTT, pH/NIR dual-responsive properties, and optimal biocompatibility. The as-fabricated JNPs exhibit satisfactory anti-cancer performance both <em>in vitro</em> and <em>in vivo</em>, and demonstrate the potential of JNPs in fluorescence imaging-guided synergistic cancer chemo-phototherapy. Overall, our research establishes a pathway in versatile inorganic/polymer JNPs for enhanced cancer diagnosis and therapy.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"187 ","pages":"Pages 328-339"},"PeriodicalIF":9.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142047626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The meniscus tissue is crucial for knee joint biomechanics and is frequently susceptible to injuries resulting in early-onset osteoarthritis. Consequently, the need for meniscal substitutes spurs ongoing development. The meniscus is a composite tissue reinforced with circumferential and radial collagenous fibers; the mechanical role of the latter has yet to be fully unveiled.
Here, we investigated the role of radial fibers using a synergistic methodology combining meniscal tissue structure imaging, a computational knee joint model, and the fabrication of simple biomimetic composite laminates. These laminates mimic the basic structural units of the meniscus, utilizing longitudinal and transverse fibers equivalent to the circumferential and radial fibers in meniscal tissue.
In the computational model, the absence of radial fibers resulted in stress concentration within the meniscus matrix and up to 800 % greater area at the same stress level. Furthermore, the contact pressure on the tibial cartilage increased drastically, affecting up to 322 % larger areas. Conversely, in models with radial fibers, we observed up to 25 % lower peak contact pressures and width changes of less than 0.1 %. Correspondingly, biomimetic composite laminates containing transverse fibers exhibited minor transverse deformations and smaller Poisson's ratios. They demonstrated structural shielding ability, maintaining their mechanical performance with the reduced amount of fibers in the loading direction, similar to the ability of the torn meniscus to carry and transfer loads to some extent. These results indicate that radial fibers are essential to distribute contact pressure and tensile stresses and prevent excessive deformations, suggesting the importance of incorporating them in novel designs of meniscal substitutes.
Statement of significance
The organization of the collagen fibers in the meniscus tissue is crucial to its biomechanical function. Radially oriented fibers are an important structural element of the meniscus and greatly affect its mechanical behavior. However, despite their importance to the meniscus mechanical function, radially oriented fibers receive minor attention in meniscal substitute designs. Here, we used a synergistic methodology that combines imaging of the meniscal tissue structure, a structural computational model of the knee joint, and the fabrication of simplistic biomimetic composite laminates that mimic the basic structural units of the meniscus. Our findings highlight the importance of the radially oriented fibers, their mechanical role in the meniscus tissue, and their importance as a crucial element in engineering novel meniscal substitutes.
{"title":"Unveiling the mechanical role of radial fibers in meniscal tissue: Toward structural biomimetics","authors":"Adi Aharonov , Shachar Sofer , Hod Bruck , Udi Sarig , Mirit Sharabi","doi":"10.1016/j.actbio.2024.08.024","DOIUrl":"10.1016/j.actbio.2024.08.024","url":null,"abstract":"<div><div>The meniscus tissue is crucial for knee joint biomechanics and is frequently susceptible to injuries resulting in early-onset osteoarthritis. Consequently, the need for meniscal substitutes spurs ongoing development. The meniscus is a composite tissue reinforced with circumferential and radial collagenous fibers; the mechanical role of the latter has yet to be fully unveiled.</div><div>Here, we investigated the role of radial fibers using a synergistic methodology combining meniscal tissue structure imaging, a computational knee joint model, and the fabrication of simple biomimetic composite laminates. These laminates mimic the basic structural units of the meniscus, utilizing longitudinal and transverse fibers equivalent to the circumferential and radial fibers in meniscal tissue.</div><div>In the computational model, the absence of radial fibers resulted in stress concentration within the meniscus matrix and up to 800 % greater area at the same stress level. Furthermore, the contact pressure on the tibial cartilage increased drastically, affecting up to 322 % larger areas. Conversely, in models with radial fibers, we observed up to 25 % lower peak contact pressures and width changes of less than 0.1 %. Correspondingly, biomimetic composite laminates containing transverse fibers exhibited minor transverse deformations and smaller Poisson's ratios. They demonstrated structural shielding ability, maintaining their mechanical performance with the reduced amount of fibers in the loading direction, similar to the ability of the torn meniscus to carry and transfer loads to some extent. These results indicate that radial fibers are essential to distribute contact pressure and tensile stresses and prevent excessive deformations, suggesting the importance of incorporating them in novel designs of meniscal substitutes.</div></div><div><h3>Statement of significance</h3><div>The organization of the collagen fibers in the meniscus tissue is crucial to its biomechanical function. Radially oriented fibers are an important structural element of the meniscus and greatly affect its mechanical behavior. However, despite their importance to the meniscus mechanical function, radially oriented fibers receive minor attention in meniscal substitute designs. Here, we used a synergistic methodology that combines imaging of the meniscal tissue structure, a structural computational model of the knee joint, and the fabrication of simplistic biomimetic composite laminates that mimic the basic structural units of the meniscus. Our findings highlight the importance of the radially oriented fibers, their mechanical role in the meniscus tissue, and their importance as a crucial element in engineering novel meniscal substitutes.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"187 ","pages":"Pages 199-211"},"PeriodicalIF":9.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142057492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1016/j.actbio.2024.08.037
Luna Gade , Ben J. Boyd , Martin Malmsten , Andrea Heinz
Inflammatory skin conditions highly influence the quality of life of the patients suffering from these disorders. Symptoms include red, itchy and painful skin lesions, which are visible to the rest of the world, causing stigmatization and a significantly lower mental health of the patients. Treatment options are often unsatisfactory, as they suffer from either low patient adherence or the risk of severe side effects. Considering this, there is a need for new treatments, and notably of new ways of delivering the drugs. Stimuli-responsive drug delivery systems are able to deliver their drug cargo in response to a given stimulus and are, thus, promising for the treatment of inflammatory skin conditions. For example, the use of external stimuli such as ultraviolet light, near infrared radiation, or alteration of magnetic field enables drug release to be precisely controlled in space and time. On the other hand, internal stimuli induced by the pathological condition, including pH alteration in the skin or upregulation of reactive oxygen species or enzymes, can be utilized to create drug delivery systems that specifically target the diseased skin to achieve a better efficacy and safety. In the latter context, however, it is of key importance to match the trigger mechanism of the drug delivery system to the actual pathological features of the specific skin condition. Hence, the focus of this article is placed not only on reviewing stimuli-responsive drug delivery systems developed to treat specific inflammatory skin conditions, but also on critically evaluating their efficacy in the context of specific skin diseases.
Statement of significance
Skin diseases affect one-third of the world's population, significantly lowering the quality of life of the patients, who deal with symptoms such as painful and itchy skin lesions, as well as stigmatization due to the visibility of their symptoms. Current treatments for inflammatory skin conditions are often hampered by low patient adherence or serious drug side effects. Therefore, more emphasis should be placed on developing innovative formulations that provide better efficacy and safety for patients. Stimuli-responsive drug delivery systems hold considerable promise in this regard, as they can deliver their cargo precisely where and when it is needed, reducing adverse effects and potentially offering better treatment outcomes.
{"title":"Stimuli-responsive drug delivery systems for inflammatory skin conditions","authors":"Luna Gade , Ben J. Boyd , Martin Malmsten , Andrea Heinz","doi":"10.1016/j.actbio.2024.08.037","DOIUrl":"10.1016/j.actbio.2024.08.037","url":null,"abstract":"<div><div>Inflammatory skin conditions highly influence the quality of life of the patients suffering from these disorders. Symptoms include red, itchy and painful skin lesions, which are visible to the rest of the world, causing stigmatization and a significantly lower mental health of the patients. Treatment options are often unsatisfactory, as they suffer from either low patient adherence or the risk of severe side effects. Considering this, there is a need for new treatments, and notably of new ways of delivering the drugs. Stimuli-responsive drug delivery systems are able to deliver their drug cargo in response to a given stimulus and are, thus, promising for the treatment of inflammatory skin conditions. For example, the use of external stimuli such as ultraviolet light, near infrared radiation, or alteration of magnetic field enables drug release to be precisely controlled in space and time. On the other hand, internal stimuli induced by the pathological condition, including pH alteration in the skin or upregulation of reactive oxygen species or enzymes, can be utilized to create drug delivery systems that specifically target the diseased skin to achieve a better efficacy and safety. In the latter context, however, it is of key importance to match the trigger mechanism of the drug delivery system to the actual pathological features of the specific skin condition. Hence, the focus of this article is placed not only on reviewing stimuli-responsive drug delivery systems developed to treat specific inflammatory skin conditions, but also on critically evaluating their efficacy in the context of specific skin diseases.</div></div><div><h3>Statement of significance</h3><div>Skin diseases affect one-third of the world's population, significantly lowering the quality of life of the patients, who deal with symptoms such as painful and itchy skin lesions, as well as stigmatization due to the visibility of their symptoms. Current treatments for inflammatory skin conditions are often hampered by low patient adherence or serious drug side effects. Therefore, more emphasis should be placed on developing innovative formulations that provide better efficacy and safety for patients. Stimuli-responsive drug delivery systems hold considerable promise in this regard, as they can deliver their cargo precisely where and when it is needed, reducing adverse effects and potentially offering better treatment outcomes.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"187 ","pages":"Pages 1-19"},"PeriodicalIF":9.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142115795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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