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
正式出版
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    Microsphere sensors for characterizing stress fields within three-dimensional extracellular matrix

    Ding X.Li M.Cheng B.Wei Z....
    13页
    查看更多>>摘要：? 2022Stress in the three-dimensional extracellular matrix is one of the key cues in regulating multiscale biological processes. Thus far, noticeable progress in methods and techniques (e.g., micropipette aspiration, AFM, and molecule probes) has been made to quantify stress in cell microenvironment at different length scales. Among them, the microsphere sensor-based method (MSS-based method) has emerged as an advantageous approach over conventional techniques in quantifying stress in situ and in vivo at cellular and supra-cellular scales. This method is implemented by seven sequential steps, including fabrication, modification, characterization, cell adhesion, imaging, displacement field extraction and stress calculation. Precise control of each step and inter-tunning between steps can provide quantitative characterization of stress field. However, detailed procedural information associated with each step and process has been scattered. This review aims to provide a comprehensive overview of MSS-based method, systematically summarizing the principles and research progresses. Firstly, the basic principles are introduced, and the specific experiment and calculation processes of MSS-based method are presented in detail. Then, recent advances and applications of this method are summarized. Finally, perspectives of the limitations and development trends of MSS-based method are discussed. This specific and comprehensive review would provide a guideline for the widespread application of MSS-based method as an advantageous method for in situ and in vivo stress characterization at cellular and supra-cellular scale within three-dimensional extracellular matrix. Statement of significance: In this review, a method based on a microsphere sensor (MSS-based method) as an advantageous approach over conventional techniques in quantifying stress in situ and in vivo at cellular and supra-cellular scales is introduced and discussed. This technique is implemented by seven sequential steps, including fabrication, modification, characterization, cell junction, imaging, displacement field extraction, and stress calculation. Precise control of each step and inter-tunning between steps can provide quantitative stress field. However, detailed procedural information associated with each step has been scattered. Thus, a comprehensive review collating recent advances and perspective discussions is a necessity to introduce a better option for quantifying the stress field in biological processes at the cellular and supra-cellular scales.
      原文链接:
    • NSTL
    • Elsevier

    Fast and reversible crosslinking of a silk elastin-like polymer

    Gonzalez-Obeso C.Rodriguez-Cabello J.C.Kaplan D.L.
    10页
    查看更多>>摘要：? 2021Elastin-like polymers (ELPs) and their chimeric subfamily the silk elastin-like polymers (SELPs) exhibit a lower critical solvation temperature (LCST) behavior in water which has been extensively studied from theoretical, computational and experimental perspectives. The inclusion of silk domains in the backbone of the ELPs effects the molecular dynamics of the elastin-like domains in response to increased temperature above its transition temperature and confers gelation ability. This response has been studied in terms of initial and long-term changes in structures, however, intermediate transition states have been less investigated. Moreover, little is known about the effects of reversible hydration on the elastin versus silk domains in the physical crosslinks. We used spectroscopic techniques to analyze initial, intermediate and long-term states of the crosslinks in SELPs. A combination of thermoanalytical and rheological measurements demonstrated that the fast reversible rehydration of the elastin motifs adjacent to the relatively small silk domains was capable of breaking the silk physical crosslinks. This feature can be exploited to tailor the dynamics of these types of crosslinks in SELPs. Statement of significance: The combination of silk and elastin in a single molecule results in synergy via their interactions to impact the protein polymer properties. The ability of the silk domains to crosslink affects the thermoresponsive properties of the elastin domains. These interactions have been studied at early and late states of the physical crosslinking, while the intermediate states were the focus of the present study to understand the reversible phase-transitions of the elastin domains over the silk physical crosslinking. The thermoresponsive properties of the elastin domains at the initial, intermediate and late states of silk crosslinking were characterized to demonstrate that reversible hydration of the elastin domains influenced the reversibility of the silk crosslinks.
      原文链接:
    • NSTL
    • Elsevier

    Macrophage membrane-functionalized nanofibrous mats and their immunomodulatory effects on macrophage polarization

    Nakkala J.R.Duan Y.Ding J.Muhammad W....
    15页
    查看更多>>摘要：? 2021Immunomodulation is an important phenomenon in the normal mammalian host response toward an injury, and plays a critical role in tissue regeneration and regenerative medicine. Different phenotypes of macrophages show an array of activation states compassing pro-inflammatory to pro-alleviating cells, which are the critical players to modulate immune response and tissue regeneration. In this study, macrophage membranes of different phenotypes (macrophages (M0), classically activated macrophages (M1) and alternatively activated macrophages (M2)) were coated onto poly-ε-caprolactone (PCL) nanofibers to acquire exterior surface proteins and similar functions of the natural membranes. In vitro results unveiled that these nanofibers, especially the M2-PCL nanofibers, can suppress the activities of inflammatory markers such as TNF-α and IL-1β, and stimulate anti-inflammatory markers such as Arg-1, IL-10 and TGF-β. In a C57BL/6 mouse model, the macrophage membrane-coated nanofibers, especially the M2-PCL nanofibers, displayed minimal cellular infiltration and low collagen deposition, increased anti-inflammatory CD206 and decreased inflammatory CD86 levels. The M2-PCL nanofibers most effectively neutralized inflammatory chemokines, regulated the expression of inflammation-associated genes as well as anti-inflammatory genes, and showed strong immunomodulatory effects than the PCL, M0-PCL and M1-PCL nanofibers. Statement of Significance: Different types of macrophage membrane-functionalized PCL nanofibers were successfully prepared and well characterized. They inherited the surface proteins imitating the source macrophages, and played an important role in limiting cellular infiltration and collagen deposition. These different macrophages and their membrane-coated nanofibers (M0-PCL, M1-PCL and M2-PCL) behaved like their respective source cells. The M2 mimicking M2-PCL nanofibers effectively polarized macrophages to M2 phenotype and decreased the expression of inflammation-associated chemokines and promoted the anti-inflammation in vitro and in vivo, which is critical for tissue regeneration. The mice implanted with the bio-mimicking M2-PCL nanofibers effectively inhibited toll like receptors signaling induced NF-kB and IRF-5 and their target genes such as Edn-1, IL-6, iNOS, TNF-α, etc. compared to the PCL, and M0-PCL and M1-PCL macrophage membrane-coated nanofibers.
      原文链接:
    • NSTL
    • Elsevier

    Patterned photocrosslinking to establish stiffness anisotropies in fibrous 3D hydrogels

    Jagiello A.Hu Q.Castillo U.Botvinick E....
    9页
    查看更多>>摘要：? 2021 The AuthorsCells are known to constantly interact with their local extracellular matrix (ECM) and respond to a variety of biochemical and mechanical cues received from the ECM. Nonetheless, comprehensive understanding of cell-ECM interactions has been elusive. Many studies rely on analysis of cell behavior on 2D substrates, which do not reflect a natural cell environment. Further, lack of dynamic control over local stiffness anisotropies and fiber alignment hinders progress in studies in naturally derived fibrous 3D cultures. Here, we present a cell-safe method of patterned photocrosslinking, which can aid in studying biological hypotheses related to mechanotransduction in 3D hydrogels. As previously described by our group, ruthenium-catalyzed photocrosslinking (RCP) of selected ECM regions promotes localized increase in stiffness mediated by focused blue laser light in a confocal microscope. In this study, we further demonstrate that RCP can induce localized strain stiffening and fiber alignment outside of the selected crosslinked region and induce stiffness anisotropy biased towards the direction of fiber alignment. MDA-MB-231 cells are shown to respond to RCP-induced changes in local ECM architecture and display directional bias towards the direction of fiber alignment, as compared to control cells. Further, the effect of patterned crosslinking on a stiffness landscape is measured using multi-axes optical tweezers active microrheology (AMR) with backscattered laser beam illumination. AMR validates RCP as a suitable tool for creating distinct stiffness anisotropies which promote directed migration of cells, further underscoring the usefulness of RCP in cell-ECM studies. Statement of significance: Studies on cell-ECM interactions in 3D cultures have often been hindered by the lack of available tools to dynamically alter local ECM stiffness and fiber alignment. Here, we present a non-invasive, cell-safe and easily applicable method of patterned photocrosslinking, which can aid in studying biological hypotheses in fibrous 3D hydrogels. Ruthenium-catalyzed crosslinking (RCP) of selected fibrin ECM regions promotes localized increase in stiffness and creates distinct stiffness anisotropies in the presence of the focused blue laser light. Outside of the crosslinked region, RCP causes fiber alignment and strain stiffening in the ECM, verified using multi-axes optical tweezers active microrheology (AMR). Following RCP, human breast cancer MDA-MB-231 exhibit directed cell migration, validating usefulness of this method in cell-ECM studies.
      原文链接:
    • NSTL
    • Elsevier

    Restoring anatomical complexity of a left ventricle wall as a step toward bioengineering a human heart with human induced pluripotent stem cell-derived cardiac cells

    Hochman-Mendez C.Mesquita F.C.P.Morrissey J.da Costa E.C....
    11页
    查看更多>>摘要：? 2021The heart is a highly complex, multicellular solid organ with energy-demanding processes that require a dense vascular network, extensive cell-cell interactions, and extracellular matrix (ECM)-mediated crosstalk among heterogeneous cell populations. Here, we describe the regeneration of left ventricular (LV) wall using decellularized whole rabbit heart scaffolds recellularized exclusively with human induced pluripotent stem cell-derived endothelial cells, cardiomyocytes, and other cardiac cell types. Cells were sequentially delivered to the scaffold using an optimized endothelial cell:cardiomyocyte media. Macroscopic assessment after 60 days showed that the LV wall of recellularized hearts was anatomically restored to full thickness from base to apex and endocardium to epicardium. Histologic analysis of the recellularized LV wall revealed a heterogeneous pool of cardiac cells containing aligned cardiac troponin T-positive cells in close contact with ECM; vessels varied from large artery-like, surrounded by smooth muscle actin+ cells, to capillary-like. Vessel patency was demonstrated after perfusion of recellularized hearts transplanted into the femoral artery bed of a pig. The construct exhibited visible beating and responded to chronotropic drug administration. These results demonstrate the ability to tissue engineer a vascularized, full-thickness LV wall with an unparalleled level of microanatomical organization and multicellular composition, using decellularized ECM and human cardiomyocytes, endothelial cells, and other cardiac cell types. Statement of significance: Decellularized extracellular matrix (ECM) is a bioactive template for tissue engineering, but recellularizing acellular whole heart scaffolds is challenging. Here, we successfully revascularized and repopulated a large, full-thickness portion of a ventricle using human induced pluripotent stem cell-derived endothelial and cardiac cells. At 60 days, histologic studies showed that the microanatomical organization and cellular composition of this region was similar to that of the native heart. The recellularized heart showed visible beating and responded appropriately to heartbeat-altering drugs. Vessels surrounded by smooth muscle cells and endothelial cells supported blood flow through the vessels of a recellularized heart that was surgically connected to a pig femoral artery. These findings move this approach closer to the possibility of clinical translation.
      原文链接:
    • NSTL
    • Elsevier

    Chirality-influenced antibacterial activity of methylthiazole- and thiadiazole-based supramolecular biocompatible hydrogels

    Baddi S.Dang-i A.Y.Huang T.Xing C....
    11页
    查看更多>>摘要：? 2022 Acta Materialia Inc.Chiral stereochemistry is a unique and fundamental strategy that determines the interaction of bacteria cells with chiral biomolecules and stereochemical surfaces. The interaction between bacteria and material surface (molecular chirality or supramolecular chirality) plays a significant role in modulating antibacterial performance. Herein, we developed inherent chiral antibacterial hydrogels by modifying the carboxyl groups of our previously reported supramolecular gelator (LPF-left handed phenylalanine gelator and DPF- right handed phenylalanine gelator) with 2-amino-5-methylthiazole (MTZ) and 5-amino-1,3,4-thiadiazole-2- thiol (TDZ). The new L/D-gelator molecules initiate self-assembly to form hydrogels through non-covalent interactions (Hydrogen bonding and π-π interactions) verified by FTIR and CD spectroscopy. Morphological studies of the xerogels revealed left and right-handed chiral nanofibers for the gelators' L-form and D-form, respectively. The resulting hydrogels exhibited inherent antibacterial activity against Gram-positive (Bacillus subtilis, Staphylococcus aureus) and Gram-negative (Pseudomonas aeruginosa) bacteria, with TDZ hydrogels showing more significant antibacterial activity than MTZ hydrogels. Interestingly, the D-form (having right-handed nanofibers) of both hydrogels (MTZ and TDZ) exhibited higher antibacterial activities compared with the left-handed nanofibrous hydrogels (L-form) attributed to the stereoselective interaction of the chiral helical nanofiber. Moreover, the amplification of chirality moving from a molecular to a supramolecular level essentially improved the antibacterial action. Our results provide deep insight into the development of unique supramolecular chiral antimicrobial agents and hint at the potentiality of right-handed nanofibers (D-form) having enhanced antibacterial activity. Statement of significance: Chiral stereochemistry plays a significant role in many biological processes, which determines the interaction of bacteria cells with chiral biomolecules. The interaction between bacteria and material surface (molecular chirality or supramolecular chirality) plays a significant role in modulating antibacterial performance. Here, we deigned and synthesized unique inherent biocompatible supramolecular chiral hydrogel. From this study we concluded that the D-form (having right-handed nanofibers) of hydrogels exhibited higher antibacterial activities compared with the left-handed nanofibrous hydrogels (L-form) attributed to the stereoselective interaction of the chiral helical nanofiber. Additionally, this study also explored the amplification of chirality moving from a molecular to a supramolecular level essentially improved the antibacterial action.
      原文链接:
    • NSTL
    • Elsevier

    Tapping basement membrane motifs: Oral junctional epithelium for surface-mediated soft tissue attachment to prevent failure of percutaneous devices

    Fischer N.G.Kobe A.C.Dai J.He J....
    19页
    查看更多>>摘要：? 2021Teeth, long-lasting percutaneous organs, feature soft tissue attachment through adhesive structures, hemidesmosomes, in the junctional epithelium basement membrane adjacent to teeth. This soft tissue attachment prevents bacterial infection of the tooth despite the rich – and harsh – microbial composition of the oral cavity. Conversely, millions of percutaneous devices (catheters, dental, and orthopedic implants) fail from infection yearly. Standard of care antibiotic usage fuels antimicrobial resistance and is frequently ineffective. Infection prevention strategies, like for dental implants, have failed in generating durable soft tissue adhesion – like that seen with the tooth – to prevent bacterial colonization at the tissue-device interface. Here, inspired by the impervious natural attachment of the junctional epithelium to teeth, we synthesized four cell adhesion peptide (CAPs) nanocoatings, derived from basement membranes, to promote percutaneous device soft tissue attachment. The two leading nanocoatings upregulated integrin-mediated hemidesmosomes, selectively increased keratinocyte proliferation compared to fibroblasts, which cannot form hemidesmosomes, and expression of junctional epithelium adhesive markers. CAP nanocoatings displayed marked durability under simulated clinical conditions and the top performer CAP nanocoating was validated in a percutaneous implant murine model. Basement membrane CAP nanocoatings, inspired by the tooth and junctional epithelium, may provide an alternative anti-infective strategy for percutaneous devices to mitigate the worldwide threat of antimicrobial resistance. Statement of significance: Prevention and management of medical device infection is a significant healthcare challenge. Overzealous antibiotic use has motivated alternative material innovations to prevent infection. Here, we report implant cell adhesion peptide nanocoatings that mimic a long-lasting, natural “medical device,” the tooth, through formation of cell adhesive structures called hemidesmosomes. Such nanocoatings sidestep the use of antimicrobial or antibiotic elements to form a soft-tissue seal around implants. The top performing nanocoatings prompted expression of hemidesmosomes and defensive factors to mimic the tooth and was validated in an animal model. Application of cell adhesion peptide nanocoatings may provide an alternative to preventing, rather that necessarily treating, medical device infection across a range of device indications, like dental implants.
      原文链接:
    • NSTL
    • Elsevier

    Construction of adipose tissue using a silica expander capsule and cell sheet-assembled of decellularized adipose tissue

    Zhu Z.Yuan Z.Guo L.Nurzat Y....
    13页
    查看更多>>摘要：? 2021 Acta Materialia Inc.Delayed neovascularization and unstable adipose formation are major confounding factors in adipose tissue engineering. A system using decellularized adipose tissue (DAT), adipose-derived stem cells (ADSCs), and human umbilical vein endothelial cells (HUVECs) has been preliminarily studied, but it requires optimization, as adipogenic and angiogenic capabilities for maintaining a stable construct shape are limited. The current study aimed to address these limitations. Our initial modification involved the addition of exogenous chemokine (C–C motif) ligand 2 (CCL2), which resulted in enhanced adipogenesis and angiogenesis. However, further improvement was required due to delayed blood recanalization. To further optimize the system, a vascularized fibrous capsule derived from an implanted silica expander was utilized as a second modification. We hypothesized this would function as both a microbioreactor to fix the seed cells and exogenous CCL2 locally and as a vascular bed to promote neovascularization. Compared with that of the CCL2 loaded ADSC-HUVECs cell sheet assembled DAT system, adding the silica expander capsule resulted in significantly increased construct stability, new vessel intensity, a greater number of Oil Red O-positive lipid droplets, more enhanced tissue remodeling, and upregulated peroxisome proliferator-activated receptor gamma (PPARγ) & leptin expression. Thus, these two modifications helped optimize the currently available ADSC-HUVEC cell sheet assembled DAT system, providing an adipose tissue construction strategy with enhanced adipogenesis and angiogenesis to reconstruct soft tissue defects. Moreover, close-to-normal leptin expression provided the engineered adipose tissue with a glucometabolic function, in addition to remodeling capabilities. Statement of significance: Delayed neovascularization and unstable adipose formation are the two major problems in tissue engineering adipose. Here, we introduced an adipose tissue engineering construction strategy using a silica expander capsule along with hADSCs-HUVECs cell sheet-assembled DAT in a CCL2-rich microenvironment. Our data suggested that CCL2 could improve angiogenesis and adipogenesis in vitro and in vivo. The addition of tissue expander capsule could further improve the stability of construction and fabricated adipose tissue with increased new vessel intensity, greater numbers of Oil Red O-positive lipid droplets, more enhanced tissue remodeling, and upregulated leptin expression. CCL2 and expander capsule can have clinical utility for soft tissue defects repair, and these two factors can be useful in other tissue engineering.
      原文链接:
    • NSTL
    • Elsevier

    Injectable self-healing cellulose hydrogel based on host-guest interactions and acylhydrazone bonds for sustained cancer therapy

    Jiang X.Zeng F.Yang X.Jian C....
    12页
    查看更多>>摘要：? 2022 Acta Materialia Inc.Tumor local chemotherapy employing injectable hydrogel reservoirs is a promising platform to achieve precise drug administration. However, balanced injectability, pH-responsiveness and long-term hydrolysis resistance of self-healing hydrogels remain appealing challenges. Herein, a modular preassembly strategy combining host-guest interactions with dynamic acylhydrazone bonds, was exploited to fabricate injectable cellulose-based hydrogels (CAAs) dressed with self-healing properties, pH-responsiveness and hydrolytic degradation resistance. Attributed to the host-guest interaction between β-cyclodextrin (CD) and 1-adamantane (AD), the hydrogels exhibited injectability, self-healing properties (healing efficiency of 97.5%) and rapid recovery (< 10 min) without external stimuli in physiological environment. Moreover, the hydrogels equipped with dynamic acylhydrazone linkages underwent slow hydrolytic degradation (> 30 days) and pH-responsive behavior, endowing the hydrogels with precise spatiotemporal drug release administration. The in vivo application of CAA as a carrier was studied using doxorubicin (DOX) model drug, and the results shows that using CAA as DOX carrier not only greatly enhances the anti-tumor efficacy of DOX, but also reduced the side effects of DOX. Statement of significance: With the preassemble approach combining host-guest interactions with dynamic acylhydrazone bonds, this work demonstrated a multi-functional self-healing hydrogel as drug carrier developed by using natural polysaccharides, which offers a new avenue for the high-value utilization of biomass. The strategy demonstrated in the present work may also supply a pathway for the preparation and regulation of hydrogels as intelligent biomedicine materials.
      原文链接:
    • NSTL
    • Elsevier

    Microscale structural changes of individual fibrin fibers during fibrinolysis

    Lynch S.R.Laverty S.M.Bannish B.E.Hudson N.E....
    9页
    查看更多>>摘要：? 2022Fibrinolysis is the enzymatic digestion of fibrin, the primary structural component in blood clots. Mechanisms of fibrin fiber digestion during lysis have long been debated and obtaining detailed structural knowledge of these processes is important for developing effective clinical approaches to treat ischemic stroke and pulmonary embolism. Using dynamic fluorescence microscopy, we studied the time-resolved digestion of individual fibrin fibers by the fibrinolytic enzyme plasmin. We found that plasmin molecules digest fibers along their entire lengths, but that the rates of digestion are non-uniform, resulting in cleavage at a single location along the fiber. Using mathematical modeling we estimated the rate of plasmin arrival at the fiber surface and the number of digestion sites on a fiber. We also investigated correlations between local fiber digestion rates, cleavage sites, and fiber properties such as initial thickness. Finally, we uncovered a previously unknown tension-dependent mechanism that pulls fibers apart during digestion. Taken together these results promote a paradigm shift in understanding mechanisms of fibrinolysis and underscore the need to consider fibrin tension when assessing fibrinolytic approaches. Statement of significance: We developed a method for interrogating lysis of individual fibrin fibers, enabling the time-resolved observation of individual fiber digestion for the first time. Our results resolve longstanding disagreements about fibrinolytic processes and reveal previously unknown mechanisms that also play a role. Also, we developed the first microscale mathematical model of plasmin-fibrin interaction, which predicts the number of plasmin molecules on each fiber and can serve as a framework for investigating novel therapeutics.
      原文链接:
    • NSTL
    • Elsevier