首页期刊导航|Acta biomaterialia
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Acta biomaterialia
Elsevier
Acta biomaterialia

Elsevier

1742-7061

Acta biomaterialia/Journal Acta biomaterialiaEIISTPSCI
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    A Peptide/MicroRNA-31 nanomedicine within an electrospun biomaterial designed to regenerate wounds in vivo

    Mulholland, E. J.McErlean, E. M.Dunne, N.McCarthy, H. O....
    16页
    查看更多>>摘要：microRNA-31 (miR-31) has been identified to be downregulated in pathologies associated with delayed wound repair. Thus, it was proposed that the delivery of a plasmid encoding miR-31 (pmiR-31) to the skin could hold potential in promoting wound healing. Effective delivery of pmiR-31 was potentiated by encapsulation with the CHAT peptide to form nanocomplexes, this improved cellular entry and elicited a potent increase in miR-31 expression in vitro in both skin human keratinocyte cell line (HaCaT) and human microvascular endothelial cell line (HMEC-1). Transfection efficiencies with CHAT/pEFGP-N1 were significant at 15.2 +/- 8.1% in HMEC-1 cells and > 40% in HaCaT cells. In this study, the CHAT/pmiR-31 nanocomplexes at a N:P ratio of 10 had an average particle size of 74.2 nm with a cationic zeta potential of 9.7 mV. Delivery of CHAT/pmiR-31 to HaCaT and HMEC-1 cells resulted in significant improvements in cell migration capacity and increased angiogenesis. In vivo studies were conducted in C57BL/6 J mice were CHAT/pmiR-31 was delivered via electrospun PVA nanofibres, demonstrating a significant increase in epidermal (increase of similar to 38.2 mu m) and stratum corneum (increase of 8.2 mu m) layers compared to con-trols. Furthermore, treatment in vivo with CHAT/pmiR-31 increased angiogenesis in wounds compared to controls, with a significant increase in vessel diameter by similar to 20.4 mu m compared against a commercial dressing control (DurafiberTM). Together, these data demonstrate that the delivery of CHAT/pmiR-31 nanocomplexes from electrospun PVA nanofibres represent an innovative therapy for wound repair, eliciting a positive therapeutic response across both stromal and epithelial tissue compartments of the skin. Statement of significance This study advances research regarding the development of our unique electrospun nanofibre patch to deliver genetic nanoparticles into wounds in vivo to promote healing. The genetic nanoparticles are comprised of: (a) plasmid micro-RNA31 that has been shown to be downregulated in pathologies with delayed wound repair and (b) a 15 amino acid linear peptide termed CHAT. The CHAT facilitates complexation of miR-31 and cellular uptake. Herein, we report for the first time on the use of CHAT to deliver a therapeutic cargo pmiR-31 for wound healing applications from a nanofibre patch. Application of the nanofibre patch resulted in the controlled delivery of the CHAT/pmiR-31 nanoparticles with a significant increase in both epidermal and stratum corneum layers compared to untreated and commercial controls. (C) 2021 The Authors. Published by Elsevier Ltd on behalf of Acta Materialia Inc.
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    Structural aspects controlling the mechanical and biological properties of tough, double network hydrogels

    Huang, YuwanJayathilaka, Pavithra B.Islam, Md SharifulTanaka, Carina B....
    12页
    查看更多>>摘要：Anticipating an increasing demand for hybrid double network (DN) hydrogels in biomedicine and biotech-nology, this study evaluated the effects of each network on the mechanical and biological properties. Polyethylene glycol (PEG) (meth)acrylate hydrogels with varied monomer molecular weights and archi-tectures (linear vs. 4-arm) were produced with and without an added ionically bonded alginate network and their mechanical properties were characterized using compression testing. The results showed that while some mechanical properties of PEG single network (SN) hydrogels decreased or changed negligibly with increasing molecular weight, the compressive modulus, strength, strain to failure, and toughness of DN hydrogels all significantly increased with increased PEG monomer molecular weight. At a fixed molec-ular weight (10 kDa), 4-arm PEG SN hydrogels exhibited better overall mechanical performance; however, this benefit was diminished for the corresponding DN hydrogels with comparable strength and toughness and lower strain to failure for the 4-arm case. Regardless of the PEG monomer structure, the alginate network made a relatively larger contribution to the overall DN mechanical properties when the covalent PEG network was looser with a larger mesh size (e.g., for larger monomer molecular weight and/or linear architecture) which presumably enabled more ionic crosslinking. Considering the biological performance, adipose derived stem cell cultures demonstrated monotonically increasing cell area and Yes-associated protein related mechanosensing with increasing amounts of alginate from 0 to 2 wt.%, demonstrating the possibility for using DN hydrogels in guiding musculoskeletal differentiation. These findings will be use-ful to design suitable hydrogels with controllable mechanical and biological properties for mechanically demanding applications. Statement of significance Hydrogels are widely used in commercial applications, and recently developed hybrid double network hydrogels have enhanced strength and toughness that will enable further expansion into more mechani-cally demanding applications (e.g., medical implants, etc.). The significance of this work is that it uncovers some key principles regarding monomer molecular weight, architecture, and concentration for developing strong and tough hybrid double network hydrogels that would not be predicted from their single net -work counterparts or a linear combination of the two networks. Additionally, novel insight is given into the biological performance of hybrid double network hydrogels in the presence of adipose derived stem cell cultures which suggests new scope for using double network hydrogels in guiding musculoskeletal differentiation. (c) 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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    Tungsten disulfide nanotubes enhance flow-induced crystallization and radio-opacity of polylactide without adversely affecting in vitro toxicity

    Ramachandran, KarthikShao, ZixuanDi Luccio, TizianaShen, Bo...
    14页
    查看更多>>摘要：Treatment of vascular disease, from peripheral ischemia to coronary heart disease (CHD), is poised for transformation with the introduction of transient implants designed to "scaffold" regeneration of blood vessels and ultimately leave nothing behind. Improved materials could expand the use of these devices. Here, we examine one of the leading polymers for bioresorbable scaffolds (BRS), polylactide (PLA), as the matrix of nanocomposites with tungsten disulfide (WS2) nanotubes (WSNT), which may provide mechanical reinforcement and enhance radio-opacity. We evaluate in vitro cytotoxicity using vascular cells, flow-induced crystallization and radio-opacity of PLA-WSNT nanocomposites at low WSNT concentration. A small amount of WSNT (0.1 wt%) can effectively promote oriented crystallization of PLA without compromising molecular weight. And radio-opacity improves significantly: as little as 0.5 to 1 wt% WSNT doubles the radio-opacity of PLA-WSNT relative to PLA at 17 keV. The results suggest that a single component, WSNT, has the potential to increase the strength of BRS to enable thinner devices and increase radio-opacity to improve intraoperative visualization. The in vitro toxicity results indicate that PLA-WSNT nanocomposites are worthy of investigation in vivo . Although substantial further preclinical studies are needed, PLA-WSNT nanocomposites may provide a complement of material properties that may improve BRS and expand the range of lesions that can be treated using transient implants. Statement of significance Bioresorbable Scaffolds (BRSs) support regeneration of arteries without permanent mechanical constraint. Poly-L-lactide (PLLA) is the structural material of the first approved BRS for coronary heart disease (ABSORB BVS), withdrawn due to adverse events in years 1-3. Here, we examine tungsten disulfide (WS2) nanotubes (WSNT) in PLA to address two contributors to early complications: (1) reinforce PLLA (enable thinner BRS), and (2) increase radiopacity (provide intraoperative visibility). For BRS, it is significant that WSNT disperse, remain dispersed, reduce friction and improve mechanical properties without additional chemicals or surface modifications. Like WS2 nanospheres, bare WSNT and PLA-WSNT nanocomposites show low cytotoxicity in vitro . PLA-WSNT show enhanced flow-induced crystallization relative to PLA, motivating future study of the processing behavior and strength of these materials. (C) 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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    • NSTL
    • Elsevier

    Centrifugally concentric ring-patterned drug-loaded polymeric coating as an intraocular lens surface modification for efficient prevention of posterior capsular opacification

    Lu, DuoduoHan, YuemeiLiu, DongChen, Siqi...
    15页
    查看更多>>摘要：Posterior capsular opacification (PCO) is the main postoperative complication after intraocular lens (IOL) implantation in cataract surgery, because of the proliferation of the residual lens epithelial cells (LECs) in the lens capsule. Drug-eluting IOLs, aimed to develop an in situ drug delivery device, are the promising concept in recent years. As IOLs are optical devices other than implants, the feasibility and applicability remain a challenge for drug-eluting coatings. In this investigation, a centrifugally concentric ring patterned drug-loaded poly(lactide-co-glycolic acid) (PLGA) coating was designed and fabricated by the spin coating technique. The concentric ring-patterned morphologies and the drug loading and release properties were carefully investigated, and the spin coating parameters were optimized. A concentric annular coating with a thin center and thick periphery was obtained, which was particularly suitable for the surface modification of IOLs, as the visual pathway of the intraocular light transmission greatly requires good light transmittance of the IOLs. IOLs with the immunosuppressant cyclosporin A (CsA)-loaded coating (CsA @ PLGA) modification were then fabricated for PCO prevention. The in vitro LECs culture results showed that the CsA @ PLGA coating-modified IOLs significantly inhibited cell proliferation and induced cell death. Western blot analysis showed that the efficient cell inhibition behavior of CsA was due to the autophagy-mediated cell death pathway. The in vivo intraocular implantation results confirmed the desired PCO inhibition effect. Thus, the centrifugally concentric ring-patterned drug-loaded PLGA coating obtained by the spin coating technique provides a simple yet effective alternative of IOL modification for PCO prevention. Statement of Significance center dot Concentric ring-patterned polymer coating, specifically for drug-eluting IOL fabrication, was developed by the spin coating technique. center dot The immunosuppressant CsA inhibited LEC proliferation through the autophagy-mediated cell death pathway. center dot Concentric ring-patterned CsA-eluting IOLs exhibited reliable in vivo PCO prevention. center dot The drug-eluting IOLs fabricated by the simple and economical spin coating technique have a great potential in clinical translation. (c) 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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    • Elsevier

    High-plex expression profiling reveals that implants drive spatiotemporal protein production and innate immune activation for tissue repair

    Gong, JingjingKolling, Fred W.Hoopes, P. JackWegst, Ulrike G. K....
    9页
    查看更多>>摘要：Surprisingly little clarity exists concerning effects of biomaterial properties on spatially localized protein expression, which drives implant success. Wound healing and tissue regeneration must be optimally supported by the implant, adsorbed proteins, immune cells, and fibroblasts; cells determine repair and functional recovery through protein production and regulation. However, not yet fully understood is how implants differentially drive spatial quantities of individual proteins both within the implant interior and the tissue surrounding it. Here we apply GeoMx (R) digital spatial profiling to site-specifically investigate protein production in porous implants. Data is collected on the location and quantity of 40 + proteins from formalin-fixed, paraffin-embedded tissue slides of anisotropic tissue scaffolds ( n = 18) with differing pore sizes (35 mu m, 53 mu m) and implantation durations (2, 14, 28 days); matching bulk gene expression data (700 + genes) is measured for identical implants. Notably, we discover fundamental spatial relationships in protein localization that in both the implant interior and the exterior are either uniquely independent or dependent of implant microstructure: dendritic cell marker CD11c and fibronectin significantly dominate the scaffold interior, while cell-to-cell adhesion marker CD34 and anti-inflammatory M2 polarization marker CD163 localize in the exterior. Lastly, collating spatial and bulk information, unique spatiotemporal expression patterns are identified for markers such as fibronectin, which are only uncoverable through spatial profiling and are otherwise hidden in bulk expression results. Together, these discoveries illustrate the critical importance of quantifying spatial expression patterns for implants, facilitating a paradigm shift in the iterative design, mechanistic understanding, and rapid assessment of biomaterials. Statement of significance Spatial localization and expression of proteins, which determine implant success, are not fully understood because quantitative high-plex profiling is challenging. Applying GeoMx (R) digital spatial profiling to site-specifically investigate protein production in porous implants, data is collected on the location and quantity of 40 + protein targets from tissue scaffolds with differing pore sizes (35 mu m, 53 mu m) and implantation durations (2, 14, 28 days). Collecting in parallel matched bulk gene expression data (700 + genes) for identical implants, we discover significant spatiotemporal expression patterns that remain otherwise hidden in differential bulk results. This new approach for the rapid assessment of biomaterials offers an enhanced mechanistic understanding and enables the tailoring of implants for superior regenerative outcomes. (C) 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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    • NSTL
    • Elsevier

    The stoic tooth root: how the mineral and extracellular matrix counterbalance to keep aged dentin stable

    Reis, MarianaAlania, YvetteLeme-Kraus, ArieneFree, Robert...
    10页
    查看更多>>摘要：Aging is a physiological process with profound impact on the biology and function of biosystems, including the human dentition. While resilient, human teeth undergo wear and disease, affecting overall physical, psychological, and social human health. However, the underlying mechanisms of tooth aging remain largely unknown. Root dentin is integral to tooth function in that it anchors and dissipates mechanical load stresses of the tooth-bone system. Here, we assess the viscoelastic behavior, composition, and ultrastructure of young and old root dentin using nano-dynamic mechanical analysis, micro-Raman spectroscopy, small angle X-ray scattering, atomic force and transmission electron microscopies. We find that the root dentin overall stiffness increases with age. Unlike other mineralized tissues and even coronal dentin, however, the ability of root dentin to dissipate energy during deformation does not decay with age. Using a deconstruction method to dissect the contribution of mineral and organic matrix, we find that the damping factor of the organic matrix does deteriorate. Compositional and ultrastructural analyses revealed higher mineral-to-matrix ratio, altered enzymatic and non-enzymatic collagen cross linking, increased collagen d-spacing and fibril diameter, and decreased abundance of proteoglycans and sulfation pattern of glycosaminoglycans . Therefore, even in the absence of remodeling, the extracellular matrix of root dentin shares traits of aging with other tissues. To explain this discrepancy, we propose that altered matrix-mineral interactions, possibly mediated by carbonate ions sequestered at the mineral interface and/or altered glycosaminoglycans counteract the deleterious effects of aging on the structural components of the extracellular matrix. Statement of significance Globally, a quarter of the population will be over 65 years old by 2050. Because many will retain their dentition, it will become increasingly important to understand and manage how aging affects teeth. Dentin is integral to the protective, biomechanical, and regenerative features of teeth. Here, we demonstrate that older root dentin not only has altered mechanical properties, but shows characteristic shifts in mineralization, composition, and post-translational modifications of the matrix. This strongly suggests that there is a mechanistic link between mineral and matrix components to the biomechanical performance of aging dentin with implications for efforts to slow or even reverse the aging process. (c) 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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    Regional variations in discrete collagen fibre mechanics within intact intervertebral disc resolved using synchrotron computed tomography and digital volume correlation

    Disney, C. M.Mo, J.Eckersley, A.Bodey, A. J....
    14页
    查看更多>>摘要：Many soft tissues, such as the intervertebral disc (IVD), have a hierarchical fibrous composite structure which suffers from regional damage. We hypothesise that these tissue regions have distinct, inherent fibre structure and structural response upon loading. Here we used synchrotron computed tomography (sCT) to resolve collagen fibre bundles (similar to 5 mu m width) in 3D throughout an intact native rat lumbar IVD under increasing compressive load. Using intact samples meant that tissue boundaries (such as endplate-disc or nucleus-annulus) and residual strain were preserved; this is vital for characterising both the inherent structure and structural changes upon loading in tissue regions functioning in a near-native environment. Nano-scale displacement measurements along > 10,0 0 0 individual fibres were tracked, and fibre orientation, curvature and strain changes were compared between the posterior-lateral region and the anterior region. These methods can be widely applied to other soft tissues, to identify fibre structures which cause tissue regions to be more susceptible to injury and degeneration. Our results demonstrate for the first time that highly-localised changes in fibre orientation, curvature and strain indicate differences in regional strain transfer and mechanical function (e.g. tissue compliance). This included decreased fibre reorientation at higher loads, specific tissue morphology which reduced capacity for flexibility and high strain at the disc-endplate boundary. Statement of significance The analyses presented here are applicable to many collagenous soft tissues which suffer from regional damage. We aimed to investigate regional intervertebral disc (IVD) structural and functional differences by characterising collagen fibre architecture and linking specific fibre-and tissue-level deformation behaviours. Synchrotron CT provided the first demonstration of tracking discrete fibres in 3D within an intact IVD. Detailed analysis of regions was performed using over 200k points, spaced every 8 mu m along 10k individual fibres. Such comprehensive structural characterisation is significant in informing future computational models. Morphological indicators of tissue compliance (change in fibre curvature and orientation) and fibre strain measurements revealed localised and regional differences in tissue behaviour. (C) 2021 The Authors. Published by Elsevier Ltd on behalf of Acta Materialia Inc.
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    Comparative tribology II-Measurable biphasic tissue properties have predictable impacts on cartilage rehydration and lubricity

    Gure, Ahmed E.Benson, Jamie M.Ortved, Kyla F.Burris, David L....
    15页
    查看更多>>摘要：Healthy articular cartilage supports load bearing and frictional properties unmatched among biological tissues and man-made bearing materials. Balancing fluid exudation and recovery under loaded and articulated conditions is essential to the tissue's biological and mechanical longevity. Our prior tribological investigations, which leveraged the convergent stationary contact area (cSCA) configuration, revealed that sliding alone can modulate cartilage interstitial fluid pressurization and the recovery and maintenance of lubrication under load through a mechanism termed 'tribological rehydration.' Our recent comparative assessment of tribological rehydration revealed remarkably consistent sliding speed-dependent fluid recovery and lubrication behaviors across femoral condyle cartilage from five mammalian species (equine/horse, bovine/cow, porcine/pig, ovine/sheep, and caprine/goat). In the present study, we identified and characterized key predictive relationships among tissue properties, sliding-induced tribological rehydration, and the modulation/recovery of lubrication within healthy articular cartilage. Using correlational analysis, we linked observed speed-dependent tribological rehydration behaviors to cartilage's geometry and biphasic properties (tensile and compressive moduli, and permeability). Together, these findings demonstrate that easily measurable biphasic tissue characteristics (e.g., bulk tissue material properties, compressive strain magnitude, and strain rates) can be used to predict cartilage's rehydration and lubricating abilities, and ultimately its function in vivo . Statement of significance In healthy cartilage, articulation recovers fluid lost to static loading thereby sustaining tissue lubricity. Osteoarthritis causes changes to cartilage composition, stiffness, and permeability associated with faster fluid exudation and presumably poorer frictional outcomes. Yet, the relationship between mechanical properties and fluid recovery during articulation/sliding remains unclear. Through innovative, high-speed benchtop sliding and indentation experiments, we found that cartilage's tissue properties regulate its exudation/hydration under slow sliding speeds but have minimal effect at high sliding speeds. In fact, cartilage rehydration appears insensitive to permeability and stiffness under high fluid load support conditions. This new understanding of the balance of cartilage exudation and rehydration during activity, based upon comparative tribology studies, may improve prevention and rehabilitation strategies for joint injuries and osteoarthritis. (c) 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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    The modes and competing rates of cartilage fluid loss and recovery

    Voinier, S.Moore, A. C.Benson, J. M.Price, C....
    8页
    查看更多>>摘要：Cartilage loses, recovers, and maintains its thickness, hydration, and biomechanical functions based on competing rates of fluid loss and recovery under varying joint-use conditions. While the mechanics and implications of load-induced fluid loss have been studied extensively, those of fluid recovery have not. This study isolates, quantifies, and compares rates of cartilage recovery from three known modes: (1) passive swelling - fluid recovery within a static unloaded contact area; (2) free swelling - unrestricted fluid recovery by an exposed surface; (3) tribological rehydration - fluid recovery within a loaded contact area during sliding. Following static loading of adult bovine articular cartilage to between 100 and 500 mu m of compression, passive swelling, free swelling, and tribological rehydration exhibited average rates of 0.11 +/- 0.04, 0.71 +/- 0.15, and 0.63 +/- 0.22 mu m/s, respectively, over the first 100 s of recovery; for comparison, the mean exudation rate just prior to sliding was 0.06 +/- 0.04 mu m/s. For this range of compressions, we detected no significant difference between free swelling and tribological rehydration rates. However, free swelling and tribological rehydration rates, those associated with joint articulation, were similar to 7-fold faster than passive swelling rates. While previous studies show how joint articulation prevents fluid loss indefinitely, this study shows that joint articulation reverses fluid loss following static loading at > 10-fold the preceding exudation rate. These competitive recovery rates suggest that joint space and function may be best maintained throughout an otherwise sedentary day using brief but regular physical activity. Statement of Significance Cartilage loses, recovers, and maintains its thickness, hydration, and biomechanical functions based on competing rates of fluid loss and recovery under varying joint-use conditions. While load-induced fluid loss is extremely well studied, this is the first to define the competing modes of fluid recovery and to quantify their rates. The results show that the fluid recovery modes associated with joint articulation are 10-fold faster than exudation during static loading and passive swelling during static unloading. The results suggest that joint space and function are best maintained throughout an otherwise sedentary day using brief but regular physical activities. (C) 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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    • NSTL
    • Elsevier

    Mechanisms of fatigue crack initiation and propagation in auxetic meta-biomaterials

    Kolken, H. M. A.Garcia, A. FontechaDu Plessis, A.Meynen, A....
    12页
    查看更多>>摘要：The fatigue performance of additively manufactured auxetic meta-biomaterials made from commercially pure titanium has been studied only recently. While certain assumptions have been made regarding the mechanisms underlying their fatigue failure, the exact mechanisms are not researched yet. Here, we studied the mechanisms of crack formation and propagation in cyclically loaded auxetic meta-biomaterials. Twelve different designs were subjected to compression-compression fatigue testing while performing full-field strain measurement using digital image correlation (DIC). The fatigue tests were stopped at different points before complete specimen failure to study the evolution of damage in the micro-architecture of the specimens using micro-computed tomography (micro-CT). Furthermore, finite element models were made to study the presence of stress concentrations. Structural weak spots were found in the inverted nodes and the vertical struts located along the outer rim of the specimens, matching the maximum principal strain concentrations and fracture sites in the DIC and micro-CT data. Cracks were often found to originate from internal void spaces or from sites susceptible to mode-I cracking. Many specimens maintained their structural integrity and exhibited no signs of rapid strain accumulation despite the presence of substantial crack growth. This observation underlines the importance of such microscale studies to identify accumulated damage that otherwise goes unnoticed. The potential release of powder particles from damaged lattices could elicit a foreign body response, adversely affecting the implant success. Finding the right failure criterion, therefore, requires more data than only those pertaining to macroscopic measurements and should always include damage assessment at the microscale. Statement of significance The negative Poisson's ratio of auxetic meta-biomaterials makes them expand laterally in response to axial tension. This extraordinary property has great potential in the field of orthopedics, where it could enhance bone-implant contact. The fatigue performance of additively manufactured auxetic metabiomaterials has only recently been studied and was found to be superior to many other bending-and stretch-dominated micro-architectures. In this study, we go beyond these macroscopic measurements and focus on the crack initiation and propagation. Full-field strain measurements and 3D imaging are used to paint a detailed picture of the mechanisms underlying fatigue. Using these data, specific aspects of the design and/or printing process can be targeted to improve the performance of auxetic meta-biomaterials in load-bearing applications. (c) 2021 The Author(s). Published by Elsevier Ltd on behalf of Acta Materialia Inc. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )
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    • Elsevier