Acta Biomaterialia最新文献

{"title":"Fe-based nanozyme with photothermal activity prepared from polymerization-induced self-assembly assays boosts the recovery of bacteria-infected wounds","authors":"Xuan Nie ,&nbsp;Ling Fu ,&nbsp;An-Pin Guo ,&nbsp;Lei Zhang ,&nbsp;Shao-Hu Huo ,&nbsp;Wen Zhang ,&nbsp;Zhao-Lin Chen ,&nbsp;Xiang Zhan ,&nbsp;Li-Qin Tang ,&nbsp;Fei Wang","doi":"10.1016/j.actbio.2024.11.003","DOIUrl":"10.1016/j.actbio.2024.11.003","url":null,"abstract":"<div><div>Nowadays, the overuse of antibiotics has escalated bacterial infections into an increasingly severe global health threat. Developing non-antibiotic treatments has emerged as a promising strategy for treating bacterial infections. Notably, nanozyme-based composite materials have garnered growing interest. Therefore, the efficient preparation of nanozyme is important. Herein, we have presented an efficient method to prepare Fe-based nanozyme through polymerization-induced self-assembly assay to kill bacteria efficiently, which could significantly enhance the healing of infected wounds. Through polymerization-induced self-assembly assay, a large number of uniformly sized micelles, bearing imidazole groups, could be efficiently prepared. These nanoparticles subsequently chelate with Fe ions, followed by pyrolysis and etching processes, resulting in the production of uniformly small-sized nanozymes with high adsorption activity in the near-infrared region. The composite materials could effectively eradicate bacteria via a synergistic strategy of photothermal and catalytic therapies under infected microenvironments. <em>In vivo</em> animal models with full-thickness wounds showed that combination therapy not only eradicates 98 % of the bacteria but also significantly accelerates wound healing. This work underscores the utility of polymerization-induced self-assembly in the preparation of nanozymes and reveals promising applications of nanozymes in wound healing.</div></div><div><h3>Statement of significance</h3><div>This research introduces a functional nanozyme with photothermal activity, synthesized through polymerization-induced self-assembly, offering a promising non-antibiotic strategy to combat bacterial infections. This strategy enhances wound healing by combining photothermal and catalytic therapies, effectively eradicating drug-resistant bacteria while minimizing damage to healthy tissue. Our findings hold significant implications for the development of advanced antibacterial treatments and offer a robust assay to prepare nanozyme with small sizes. The prepared functional nanoparticles have a potential in wound healing, addressing a critical need in the face of rising antibiotic resistance.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"190 ","pages":"Pages 488-500"},"PeriodicalIF":9.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634074","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}

{"title":"Oxidation of a zirconium nitride multilayer-covered knee implant after two years in clinical use","authors":"Julia S. Rau ,&nbsp;Gustav Eriksson ,&nbsp;Per Malmberg ,&nbsp;Ana Laura Puente Reyna ,&nbsp;Jens Schwiesau ,&nbsp;Martin Andersson ,&nbsp;Mattias Thuvander","doi":"10.1016/j.actbio.2024.10.034","DOIUrl":"10.1016/j.actbio.2024.10.034","url":null,"abstract":"<div><div>The surface composition and microstructure of an up to 5 µm thick multilayer on a knee implant were investigated. When the implant was explanted after approximately two years of clinical use due to failure from aseptic loosening, the topmost ZrN layer was found to be oxidized. Interestingly, only the non-articulating area was visibly oxidized (color change).</div><div>Up until then, the formation and characteristics of the oxide and its influence on the tribological performance remained uncertain. The oxide was thoroughly analyzed using transmission electron microscopy (TEM) and atom probe tomography (APT). The articulating and non-articulating areas were compared with an as-fabricated implant, which served as a reference. The results show that a thin oxide was also present on the articulating surface. All measured oxides were thicker than expected from native oxidation. The oxygen content of the majority of the oxide, measured with energy dispersive X-ray spectroscopy (EDS) and APT, was lower than required for the stable ZrO₂ form. Underneath the oxide, the ZrN layer remained unaffected, demonstrating the oxide's effective passivating behavior against further oxidation. No cobalt from the substrate was detected within the ZrN layer, proving the multilayer's excellent barrier function against ion release from the base metal.</div></div><div><h3>Statement of significance</h3><div>In our aging society, the use of artificial knee implants is widespread. Implant failure is not only costly, but often connected with pain for the patient and inevitably involves the implantation of a new joint. Hence, understanding the origin of joint failure is of high importance to extend the lifetime of the implant. In this research, we investigate the influence of a surface oxide, formed on an explant which failed after ∼ 2 years, on the multilayer stability. As a novelty, we focus not on the wear of the polyethylene gliding surface but on the formed oxide. The use of high-resolution analysis techniques allowed us to get a glimpse on the ongoing mechanisms at the explants surface.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"190 ","pages":"Pages 593-604"},"PeriodicalIF":9.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514434","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}

{"title":"Targeted no-releasing L-arginine-induced hesperetin self-assembled nanoparticles for ulcerative colitis intervention","authors":"Xuesong Chi ,&nbsp;Tao Chen ,&nbsp;Fengxian Luo ,&nbsp;Runan Zhao ,&nbsp;Yangjing Li ,&nbsp;Shumeng Hu ,&nbsp;Yanfei Li ,&nbsp;Wen Jiang ,&nbsp;LiHang Chen ,&nbsp;Di Wu ,&nbsp;Yinan Du ,&nbsp;Jiangning Hu","doi":"10.1016/j.actbio.2024.10.037","DOIUrl":"10.1016/j.actbio.2024.10.037","url":null,"abstract":"<div><div>Overproduction of reactive oxygen species (ROS) plays a crucial role in initiating and advancing ulcerative colitis (UC), and the persistent cycle between ROS and inflammation accelerates disease development. Therefore, developing strategies that can effectively scavenge ROS and provide targeted intervention are crucial for the management of UC. In this study, we synthesized natural carrier-free nanoparticles (HST-Arg NPs) using the Mannich reaction and π-π stacking for the intervention of UC. HST-Arg NPs are an oral formulation that exhibit good antioxidant capabilities and gastrointestinal stability. Benefiting from the negatively charged characteristics, HST-Arg NPs can specifically accumulate in positively charged inflamed regions of the colon. Furthermore, in the oxidative microenvironment of colonic inflammation, HST-Arg NPs respond to ROS by releasing nitric oxide (NO). In mice model of UC induced by dextran sulfate sodium (DSS), HST-Arg NPs significantly mitigated colonic injury by modulating oxidative stress, lowering pro-inflammatory cytokines, and repairing intestinal barrier integrity. In summary, this convenient and targeted oral nanoparticle can effectively scavenge ROS at the site of inflammation and achieve gas intervention, offering robust theoretical support for the development of subsequent oral formulations in related inflammatory interventions.</div></div><div><h3>Statement of significance</h3><div>Nanotechnology has been extensively explored in the biomedical field, but the application of natural carrier-free nanotechnology in this area remains relatively rare. In this study, we developed a natural nanoparticle system based on hesperetin (HST), L-arginine (L-Arg), and vanillin (VA) to scavenge ROS and alleviate inflammation. In the context of ulcerative colitis (UC), the synthesized nanoparticles exhibited excellent intervention effects, effectively protecting the colon from damage. Consequently, these nanoparticles provide a promising and precise nutritional intervention strategy by addressing both oxidative stress and inflammatory pathways simultaneously, demonstrating significant potential for application.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"190 ","pages":"Pages 560-578"},"PeriodicalIF":9.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514436","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}

{"title":"Exploring tissue permeability of brain tumours in different grades: Insights from pore-scale fluid dynamics analysis","authors":"Yi Yang ,&nbsp;Tian Yuan ,&nbsp;Ciprian Panaitescu ,&nbsp;Rui Li ,&nbsp;Kejian Wu ,&nbsp;Yingfang Zhou ,&nbsp;Dubravka Pokrajac ,&nbsp;Daniele Dini ,&nbsp;Wenbo Zhan","doi":"10.1016/j.actbio.2024.11.005","DOIUrl":"10.1016/j.actbio.2024.11.005","url":null,"abstract":"<div><div>Interstitial fluid (ISF) flow is identified as an essential physiological process that plays an important role in the development and progression of brain tumours. However, the relationship between the permeability of the tumour tissue, a complex porous medium, and the interstitial fluid flow around the tumour cells at the microscale is not well understood. To shed light on this issue, and in the absence of experimental techniques that can provide direct measurements, we develop a computational model to predict the tissue permeability of brain tumours in different grades by analysing the ISF flow at the pore scale. The 3-D geometrical models of tissue extracellular spaces are digitally reconstructed for each grade tumour based on their morphological properties measured from microscopic images. The predictive accuracy of the framework is validated by experimental results reported in the literature. Our results indicate that high-grade brain tumours are less permeable despite their higher porosity, whereas necrotic areas of glioblastoma are more permeable than the viable tumour areas. This implies that tissue permeability is primarily governed by both tissue porosity and the deposition of hyaluronic acid (HA), a key component of the extracellular matrix, while the HA deposition can have a greater effect than macro-level porosity. Parametric studies show that tissue permeability falls exponentially with increasing HA concentration in all grades of brain tumours, and this can be captured using an empirically derived relationship in a quantitative manner. These findings provide an improved understanding of the hydraulic properties of brain tumours and their intrinsic links to tumour microstructure. This work can be used to reveal the intratumoural physiochemical processes that rely on fluid flow and offer a powerful tool to tune textured and porous biomaterials for desired transport properties.</div></div><div><h3>Statement of Significance</h3><div>Interstitial fluid flow in the extracellular space of brain tumours plays a crucial role in their progression, development, and response to drug treatments. However, the mechanisms of interstitial fluid transport around tumour cells and the characterization of these microscale transports at the tissue scale to meet clinical requirements are largely unknown. In the absence of advanced experimental techniques to capture these pore-scale transport phenomena, we have developed and validated a computational framework to successfully reveal these phenomena across all grades of brain tumours. For the first time, we have quantitatively determined the tissue permeability of all grades of brain tumours as a function of the concentration of hyaluronic acid, a key component of the extracellular matrix. This framework will enhance our ability to capture the intratumoural physicochemical processes in brain tumours and correlate them with tumour tissue-scale behaviours.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"190 ","pages":"Pages 398-409"},"PeriodicalIF":9.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634061","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}

{"title":"Insights into heat treatments of biodegradable Mg-Y-Nd-Zr alloys in clinical settings: Unveiling roles of β' and β1 nanophases and latent in vivo hydrogen evolution","authors":"Matthew Dargusch ,&nbsp;Yuan Wang ,&nbsp;Chuhan Sha ,&nbsp;Nan Yang ,&nbsp;Xingrui Chen ,&nbsp;Jeffrey Venezuela ,&nbsp;Joseph Otte ,&nbsp;Sean Johnston ,&nbsp;Cora Lau ,&nbsp;Rachel Allavena ,&nbsp;Karine Mardon ,&nbsp;Ingrid McCaroll ,&nbsp;Julie Cairney","doi":"10.1016/j.actbio.2024.10.047","DOIUrl":"10.1016/j.actbio.2024.10.047","url":null,"abstract":"<div><div>Heat treatment serves as a viable strategy to effectively mitigate the intense corrosion of biodegradable WE43 alloys. However, limited comprehension of the passivation mechanisms underlying heat treatment and the dilemma to quantitatively examine the evolution of hydrogen gas <em>in vivo</em> introduce uncertainties in designing heat treatments for developing clinically applicable WE43. This work aims to advance this knowledge by applying cutting-edge atom probe tomography to provide atomic-scale insights into the passivation roles of rare earth (RE)-rich β₁ (Mg₃(Y, Nd)) and β' (Mg₁₂NdY) nanophases induced by T6 heat treatment at 250 °C, and employing machine learning-based image analysis techniques to quantitatively unveil WE43’s <em>in vivo</em> gas evolution during a 12-week implantation. It was found that nanosized β₁ and β' phases can effectively improve WE43′s corrosion resistance by inducing an accelerated passivation effect on the surface and confining the distribution of hydrogen ions in the matrix. Female rats presented slightly higher corrosion rates than male rats in weeks 1 and 4 but lower hydrogen gas volumes <em>in vivo</em>, while male rats possessed a superior ability to metabolise hydrogen gas <em>in vivo</em>. Notably, latent gas evolution against the corrosion rates was found which peaked at week 4 and subsided at week 12 despite the gradually decreased corrosion rates from week 1 to 12. This study offers insights for engineering heat treatments to develop clinically applicable WE43 with acceptable corrosion rates and <em>in vivo</em> gas generation at various implantation stages.</div></div><div><h3>Statement of Significance</h3><div>The study aimed to reveal the role of β₁ and β' nanophases on the good corrosion resistance of WE43. The influence of these nanophases on WE43′s corrosion performance has not been totally understood. Similarly, the understanding of hydrogen gas evolution as it relates to the magnesium implant's corrosion rate lacks clarity. Atom probe tomography (APT) indicates β₁ and β' nanophases trap hydrogen, removing H₂ from the lattice and disabling its catalytic role in Mg oxidation. Machine learning-aided analyses of computed tomography (CT) scan images indicate latent gas evolution, contradicting the monotonic <em>in vivo</em> H₂ evolution that is widely accepted.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"190 ","pages":"Pages 605-622"},"PeriodicalIF":9.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634247","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}

{"title":"Medium-entropy Zr–Nb–Ti alloys with low magnetic susceptibility, high yield strength, and low elastic modulus through spinodal decomposition for bone-implant applications","authors":"Zhaolin Hua ,&nbsp;Dechuang Zhang ,&nbsp;Lin Guo ,&nbsp;Sihan Lin ,&nbsp;Yuncang Li ,&nbsp;Cuie Wen","doi":"10.1016/j.actbio.2024.11.001","DOIUrl":"10.1016/j.actbio.2024.11.001","url":null,"abstract":"<div><div>Medium-entropy Zr–Nb–Ti (ZNT) alloys are being extensively investigated as load-bearing implant materials because of their exceptional biocompatibility and corrosion resistance, and low magnetic susceptibility. Nevertheless, enhancing their yield strength while simultaneously decreasing their elastic modulus presents a formidable obstacle, significantly constraining their broader utilization as metallic biomaterials. In this study, three medium-entropy ZNT alloys, i.e., Zr₄₅Nb₄₅Ti₁₀, Zr_42.5Nb_42.5Ti₁₅, and Zr₄₀Nb₄₀Ti₂₀ (denoted ZNT₁₀, ZNT₁₅, and ZNT₂₀, respectively), were designed based on the miscibility gap in the ZNT phase diagram and prepared by annealing of cold-rolled ingots. Their microstructures, mechanical properties, wear resistance, corrosion resistance, magnetic susceptibility, and biocompatibility were systematically studied. Spinodal decomposition occurred in the cold-rolled ZNT₁₀ and ZNTi₁₅ after annealing at 650 °C for 2 h and resulted in nanoscale Zr-rich β₁ and (Nb, Ti)-rich β₂ phases, which significantly improved their yield strength and reduced their elastic modulus. The wear resistance of the alloys decreased with an increase in Ti content. Dense ZrO₂, Nb₂O₅, and TiO₂ oxide layers were formed during the polarization process in Hanks’ solution, which enhanced the corrosion resistance of the alloys. These ZNT alloys exhibited significantly lower magnetic susceptibility than medical Ti alloys. The ZNT alloys showed a cell viability of more than 94 % toward MG-63 cells after culturing for 3 d Overall, the spinodal ZNT₁₅ showed the best combination of mechanical properties, wear resistance, corrosion resistance, low magnetic susceptibility, and sufficient biocompatibility among the three alloys.</div></div><div><h3>Statement of significance</h3><div>This work reports on medium-entropy Zr–Nb–Ti (ZNT) alloys with heterostructure. Spinodal decomposition significantly improved their mechanical strength and reduced the elastic modulus of the alloys. The wear resistance of the ZNT alloys decreased with an increase in Ti content. Dense ZrO₂, Nb₂O₅, and TiO₂ oxide layers were formed during the polarization process in Hanks’ solution, which enhanced the corrosion resistance of the alloys. The ZNT alloys exhibited significantly lower magnetic susceptibility than medical Ti alloys. The ZNT alloys showed a cell viability of &gt;94 % toward MG-63 cells after culturing for 3 d The results demonstrate that spinodal ZNT alloys have enormous potential as bone-implant materials due to their outstanding overall mechanical properties, high corrosion resistance, wear resistance, low magnetic susceptibility, and sufficient biocompatibility.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"190 ","pages":"Pages 623-641"},"PeriodicalIF":9.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634262","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}

{"title":"Comparing continuum and direct fiber models of soft tissues: An ocular biomechanics example reveals that continuum models may artificially disrupt the strains at both the tissue and fiber levels","authors":"Xuehuan He ,&nbsp;Mohammad R. Islam ,&nbsp;Fengting Ji ,&nbsp;Bingrui Wang ,&nbsp;Ian A. Sigal","doi":"10.1016/j.actbio.2024.10.019","DOIUrl":"10.1016/j.actbio.2024.10.019","url":null,"abstract":"<div><div>Collagen fibers are the main load-bearing component of soft tissues but difficult to incorporate into models. Whilst simplified homogenization models suffice for some applications, a thorough mechanistic understanding requires accurate prediction of fiber behavior, including both detailed fiber-level strains and long-distance transmission. Our goal was to compare the performance of a continuum model of the optic nerve head (ONH) built using conventional techniques with a fiber model we recently introduced which explicitly incorporates the complex 3D organization and interaction of collagen fiber bundles [<span><span>1</span></span>]. To ensure a fair comparison, we constructed the continuum model with identical geometrical, structural, and boundary specifications as for the fiber model. We found that: 1) although both models accurately matched the intraocular pressure (IOP)-induced globally averaged displacement responses observed in experiments, they diverged significantly in their ability to replicate specific 3D tissue-level strain patterns. Notably, the fiber model faithfully replicated the experimentally observed depth-dependent variability of radial strain, the ring-like pattern of meridional strain, and the radial pattern of circumferential strain, whereas the continuum model failed to do so; 2) the continuum model disrupted the strain transmission along each fiber, a feature captured well by the fiber model. These results demonstrate limitations of the conventional continuum models that rely on homogenization and affine deformation assumptions, which render them incapable of capturing some complex tissue-level and fiber-level deformations. Our results show that the strengths of explicit fiber modeling help capture intricate ONH biomechanics. They potentially also help modeling other fibrous tissues.</div></div><div><h3>Statement of significance</h3><div>Understanding the mechanics of fibrous tissues is crucial for advancing knowledge of various diseases. This study uses the ONH as a test case to compare conventional continuum models with fiber models that explicitly account for the complex fiber structure. We found that the fiber model captured better the biomechanical behaviors at both the tissue level and the fiber level. The insights gained from this study demonstrate the significant potential of fiber models to advance our understanding of not only glaucoma pathophysiology but also other conditions involving fibrous soft tissues. This can contribute to the development of therapeutic strategies across a wide range of applications.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"190 ","pages":"Pages 317-328"},"PeriodicalIF":9.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482758","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}

{"title":"Rupture mechanics of blood clots: Influence of fibrin network structure on the rupture resistance","authors":"Ranjini K. Ramanujam ,&nbsp;Farkhad Maksudov ,&nbsp;Rebecca A. Risman ,&nbsp;Rustem I. Litvinov ,&nbsp;John W. Weisel ,&nbsp;John L. Bassani ,&nbsp;Valeri Barsegov ,&nbsp;Prashant K. Purohit ,&nbsp;Valerie Tutwiler","doi":"10.1016/j.actbio.2024.10.004","DOIUrl":"10.1016/j.actbio.2024.10.004","url":null,"abstract":"<div><div>Embolization is a leading cause of mortality, yet we know little about clot rupture mechanics. Fibrin provides the main structural and mechanical stability to blood clots. Previous studies have shown that altering the concentration of coagulation activators (thrombin or tissue factor (TF)) has a significant impact on fibrin structure and viscoelastic properties, but their effects on rupture properties are mostly unknown. Toughness, which corresponds to the ability to resist rupture, is independent of viscoelastic properties. We used varying TF concentrations to alter the structure and toughness of human plasma clots. We performed single-edge notch rupture tests to examine fibrin toughness under a constant strain rate and we assessed viscoelastic mechanics using rheology. We utilized fluorescent confocal and scanning electron microscopy (SEM) to quantify the fibrin network structure under varying TF concentrations. Our results revealed that increased TF concentration resulted in increased number of fibrin fibers with a reduction in network pore size, thinner and shorter fibrin fibers. Increasing TF concentration yielded a maximum toughness at mid-TF concentration, such that fibrin diameter and number of fibers underlie a complex role in influencing the rupture resistance of blood clots, resulting in a nonmonotonic relationship between TF and toughness. A simple mechanical model, built on our findings from our Fluctuating Spring (FS) computational model, adopted to estimate the fracture toughness (critical energy release rate) as a function of TF predicts trends that are in good agreement with experiments. The differences in mechanical responses point to the importance of studying the structure-function relationships of fibrin networks, which may be predictive of the tendency for embolization.</div></div><div><h3>Statement of significance</h3><div>Fibrin, a naturally occurring biomaterial, is the main mechanical and structural scaffold of blood clots that provides the necessary strength and stability to the clot, ensuring effective stemming of bleeding. The rupture of blood clots can result in the blockage of downstream vessels thereby blocking blood flow and oxygen supply. The fibrin network structure has been shown to influence the viscoelastic mechanical properties of clots, but has not been explored for fracture mechanics. Here, we modulate the fibrin network structure by varying the concentration of Tissue Factor (TF). Interestingly, the association between TF concentration and maximum toughness of the clots is non-monotonic. The variations in mechanical responses highlight the importance of studying the structure-function relationships of fibrin networks, as these may predict the tendency for embolization.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"190 ","pages":"Pages 329-343"},"PeriodicalIF":9.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482776","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}

{"title":"Nanofibrous 3D scaffolds capable of individually controlled BMP and FGF release for the regulation of bone regeneration","authors":"Kunal J. Rambhia ,&nbsp;Hongli Sun ,&nbsp;Kai Feng ,&nbsp;Rahasudha Kannan ,&nbsp;Yasmine Doleyres ,&nbsp;Jeremy M. Holzwarth ,&nbsp;Mikayla Doepker ,&nbsp;Renny T Franceschi ,&nbsp;Peter X Ma","doi":"10.1016/j.actbio.2024.10.044","DOIUrl":"10.1016/j.actbio.2024.10.044","url":null,"abstract":"<div><div>The current clinical applications of bone morphogenetic proteins (BMPs) are limited to only a few specific indications. Locally controlled delivery of combinations of growth factors can be a promising strategy to improve BMP-based bone repair. However, the success of this approach requires the development of an effective release system and the correct choice of growth factors capable of enhancing BMP activity. Basic fibroblast growth factor (bFGF, also known as FGF-2) has shown promise in promoting bone repair, although conflicting results have been reported. Considering the complex biological activities of FGF-2, we hypothesized that FGF-2 can promote BMP-induced bone regeneration only if the dosage and kinetic parameters of the two factors are individually tailored. In this study, we conducted systematic in vitro studies on cell proliferation, differentiation, and mineralization in response to factor dose, delivery mode (sequential or simultaneous), and release rate. Subsequently, we designed individually controlled BMP-7 and FGF-2 release poly(lactide-co-glycolide) (PLGA) nanospheres attached to the poly(<span>l</span>-lactic acid) (PLLA) nanofibrous scaffolds. The data showed that BMP-7-induced bone formation was accelerated by a relatively higher FGF-2 dose (100 ng/scaffold) delivered at a faster release rate, or by a relatively lower FGF-2 dose (10 ng/scaffold) at a slower release rate in an in vivo bone regeneration model. In contrast, a very high dose of FGF-2 (1000 ng/scaffold) inhibited bone regeneration under all conditions. In vitro and in vivo data suggest that FGF-2 improved BMP-7-induced bone regeneration by coordinating FGF-2 dosage and release kinetics to enhance stem cell migration, proliferation, and angiogenesis.</div></div><div><h3>Statement of significance</h3><div>Bone morphogenetic proteins (BMPs) are the most potent growth/differentiation factors in bone development and regeneration. However, the clinical applications of BMPs have been limited to only a few specific indications due to the required supraphysiological dosages with the current BMP products and their side effects. Locally controlled delivery of BMPs and additional growth factors that can enhance their osteogenic potency are highly desired. However, different growth factors act with different mechanisms. Here we report a nanofibrous scaffold that mimics collagen in size and geometry and is immobilized with biodegradable nanospheres to achieve local and distinct release profiles of BMP7 and FGF2. Systematic studies demonstrated low dose BMP7 and FGF2 with different temporal release profiles can optimally enhance bone regeneration.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"190 ","pages":"Pages 50-63"},"PeriodicalIF":9.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142565054","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}

{"title":"Cell mediated reactions create TGF-β delivery limitations in engineered cartilage","authors":"Sedat Dogru,&nbsp;Gabriela M. Alba,&nbsp;Kirk C. Pierce,&nbsp;Tianbai Wang,&nbsp;Danial Sharifi Kia,&nbsp;Michael B. Albro","doi":"10.1016/j.actbio.2024.10.032","DOIUrl":"10.1016/j.actbio.2024.10.032","url":null,"abstract":"&lt;div&gt;&lt;div&gt;During native cartilage development, endogenous TGF-β activity is tightly regulated by cell-mediated chemical reactions in the extracellular milieu (e.g., matrix and receptor binding), providing spatiotemporal control in a manner that is localized and short acting. These regulatory paradigms appear to be at odds with TGF-β delivery needs in tissue engineering (TE) where administered TGF-β is required to transport long distances or reside in tissues for extended durations. In this study, we perform a novel examination of the influence of cell-mediated reactions on the spatiotemporal distribution of administered TGF-β in cartilage TE applications. Reaction rates of TGF-β binding to cell-deposited ECM and TGF-β internalization by cell receptors are experimentally characterized in bovine chondrocyte-seeded tissue constructs. TGF-β binding to the construct ECM exhibits non-linear Brunauer–Emmett–Teller (BET) adsorption behavior, indicating that as many as seven TGF-β molecules can aggregate at a binding site. Cell-mediated TGF-β internalization rates exhibit a biphasic trend, following a Michaelis–Menten relation (&lt;span&gt;&lt;math&gt;&lt;msub&gt;&lt;mi&gt;V&lt;/mi&gt;&lt;mrow&gt;&lt;mi&gt;m&lt;/mi&gt;&lt;mi&gt;a&lt;/mi&gt;&lt;mi&gt;x&lt;/mi&gt;&lt;/mrow&gt;&lt;/msub&gt;&lt;/math&gt;&lt;/span&gt; = 2.4 molecules cell&lt;sup&gt;-1&lt;/sup&gt; s&lt;sup&gt;-1&lt;/sup&gt;, &lt;span&gt;&lt;math&gt;&lt;msub&gt;&lt;mi&gt;K&lt;/mi&gt;&lt;mi&gt;m&lt;/mi&gt;&lt;/msub&gt;&lt;/math&gt;&lt;/span&gt; = 1.7 ng mL&lt;sup&gt;-1&lt;/sup&gt;) at low ligand doses (≤130 ng/mL), but exhibit an unanticipated non-saturating power trend at higher doses (≥130 ng/mL). Computational models are developed to illustrate the influence of these reactions on TGF-β spatiotemporal delivery profiles for conventional TGF-β administration platforms. For TGF-β delivery via supplementation in culture medium, these reactions give rise to pronounced steady state TGF-β spatial gradients; TGF-β concentration decays by ∼90 % at a depth of only 500 μm from the media-exposed surface. For TGF-β delivery via heparin-conjugated affinity scaffolds, cell mediated internalization reactions significantly reduce the TGF-β scaffold retention time (160–360-fold reduction) relative to acellular heparin scaffolds. This work establishes the significant limitations that cell-mediated chemical reactions engender for TGF-β delivery and highlights the need for novel delivery platforms that account for these reactions to achieve optimal TGF-β exposure profiles.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Statement of significance&lt;/h3&gt;&lt;div&gt;During native cartilage development, endogenous TGF-β activity is tightly regulated by cell-mediated chemical reactions in the extracellular milieu (e.g., matrix and receptor binding), providing spatiotemporal control in a manner that is localized and short acting. However, the effect of these reactions on the delivery of exogenous TGF-β to engineered cartilage tissues remains not well understood. In this study, we demonstrate that cell-mediated reactions significantly restrict the delivery of TGF-β to cells in engineered cartilage tissue constructs. For delivery via media supplem","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"190 ","pages":"Pages 178-190"},"PeriodicalIF":9.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514418","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}