查看更多>>摘要：B cells play multiple roles in immune responses related to autoimmune diseases as well as different types of cancers. As such, strategies focused on B cell targeting attracted wide interest and developed inten-sively. There are several common mechanisms various B cell targeting therapies have relied on, including direct B cell depletion, modulation of B cell antigen receptor (BCR) signaling, targeting B cell survival fac-tors, targeting the B cell and T cell costimulation, and immune checkpoint blockade. Nanocarriers, used as drug delivery vehicles, possess numerous advantages to low molecular weight drugs, reducing drug toxicity, enhancing blood circulation time, as well as augmenting targeting efficacy and improving thera-peutic effect. Herein, we review the commonly used targets involved in B cell targeting approaches and the utilization of various nanocarriers as B cell-targeted delivery vehicles. Statement of significance As B cells are engaged significantly in the development of many kinds of diseases, utilization of nanomedicines in B cell depletion therapies have been rapidly developed. Although numerous studies focused on B cell targeting have already been done, there are still various potential receptors awaiting further investigation. This review summarizes the most relevant studies that utilized nanotechnologies associated with different B cell depletion approaches, providing a useful tool for selection of receptors, agents and/or nanocarriers matching specific diseases. Along with uncovering new targets in the func-tion map of B cells, there will be a growing number of candidates that can benefit from nanoscale drug delivery. (c) 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
查看更多>>摘要：The development of biocompatible materials with desired functions is essential for tissue engineering and biomedical applications. Hydrogels prepared from these materials represent an important class of soft matter for mimicking extracellular environments. In particular, dynamic hydrogels with responsive-ness to environments are quite appealing because they can match the dynamics of biological processes. Among the external stimuli that can trigger responsive hydrogels, light is considered as a clean stimulus with high spatiotemporal resolution, complete bioorthogonality, and fine tunability regarding its wave-length and intensity. Therefore, photoresponsiveness has been broadly encoded in hydrogels for biological applications. Moreover, light can be used to initiate gelation during the fabrication of biocompatible hy-drogels. Here, we present a critical review of light manipulation tools for the fabrication of hydrogels and for the regulation of physicochemical properties and functions of photoresponsive hydrogels. The mate -rials, photo-initiated chemical reactions, and new prospects for light-induced gelation are introduced in the former part, while mechanisms to render hydrogels photoresponsive and their biological applications are discussed in the latter part. Subsequently, the challenges and potential research directions in this area are discussed, followed by a brief conclusion. Statement of significance Hydrogels play a vital role in the field of biomaterials owing to their water retention ability and biocom-patibility. However, static hydrogels cannot meet the dynamic requirements of the biomedical field. As a stimulus with high spatiotemporal resolution, light is an ideal tool for both the fabrication and operation of hydrogels. In this review, light-induced hydrogelation and photoresponsive hydrogels are discussed in detail, and new prospects and emerging biological applications are described. To inspire more research studies in this promising area, the challenges and possible solutions are also presented. (c) 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
查看更多>>摘要：Our contributions to mesoporous silica materials in the field of biomedicine are reported in this article. This perspective article represents our work in the basics of the material, preparing different ranges of mesoporous silica nanoparticles with different diameters and with varied pore sizes. We demonstrated the high loading capacity of these materials. Additionally, the possibility of functionalizing both internal and external surface with different organic or inorganic moieties allowed the development of stimuli responsive features which allowed a proper control on the administered dose. In addition, we have demonstrated that these carriers are not toxic, and we have also ensured that the load reaches its destination without affecting healthy tissues. Statement of significance This paper presents my personal opinion and background on a hot topic as mesoporous silica nanoparticles for drug delivery. To this aim it provides a comprehensive and historical overview on the innovative contributions of my research group to this rapidly expanding field of research. (c) 2021 The Author. Published by Elsevier Ltd on behalf of Acta Materialia Inc. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )
查看更多>>摘要：Full-thickness wounds to the eye can lead to serious vision impairment. Current standards of care (from suturing to tissue transplantation) usually require highly skilled surgeons and use of an operating theater. In this study, we report the synthesis, optimization, and in vitro and ex vivo testing of photocrosslinkable hydrogel-based adhesive patches that can easily be applied to globe injuries or corneal incisions. According to the type and concentration of polymers used in the adhesive formulations, we were able to finely tune the physical properties of the bioadhesive including viscosity, elastic modulus, extensibility, ultimate tensile strength, adhesion, transparency, water content, degradation time, and swellability. Our in vitro studies showed no sign of cytotoxicity of the hydrogels. Moreover, the hydrogel patches showed higher adhesion on freshly explanted pig eyeballs compared to a marketed ocular sealant. Finally, ex vivo feasibility studies showed that the hydrogel patches could seal complex open-globe injuries such as large incision, cruciform injury, and injury associated with tissue loss. These results suggest that our photocrosslinkable hydrogel patch could represent a promising solution for the sealing of open-globe injuries or surgical incisions. Statement of significance Current management of severe ocular injuries require advanced surgical skills and access to an operating theater. To address the need for emergent management of wounds that cannot be handled in the operating room, surgical adhesives have gained popularity, but none of the currently available adhesives have optimal bioavailability, adhesive or mechanical properties. This study describes the development, optimization and testing of a light-sensitive adhesive patch that can easily be applied to the eye. After solidification using visible light, the patch shows no toxicity and is more adherent to the tissue than a marketed sealant. Thus this technology could represent a promising solution to stabilize ocular injuries in emergency settings before definitive surgical repair. (c) 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
查看更多>>摘要：The main propose of this study is to characterize the impact of chronological aging on mechanical, structural, biochemical, and morphological properties of type I collagen. We have developed an original approach combining a stress-strain measurement device with a portable Raman spectrometer to enable simultaneous measurement of Raman spectra during stress vs strain responses of young adult, adult and old rat tail tendon fascicles (RTTFs). Our data showed an increase in all mechanical properties such as Young's modulus, yield strength, and ultimate tensile strength with aging. At the molecular level, Raman data revealed that the most relevant frequency shift was observed at 938 cm(-1) in Old RTTFs, which is assigned to the C-C. This suggested a long axis deformation of the peptide chains in Old RTTFs during tensile stress. In addition, the intensity of the band at 872 cm(-1), corresponding to hydroxyproline decreased for young adult RTTFs and increased for the adult ones, while it remained unchanged for Old RTTFs during tensile stress. The amide III band (1242 and 1265 cm(-1)) as well as the band ratios I-1631 / I-1663 and I-1645 / I-1663 responses to tensile stress were depending on mechanical phases (toe, elastic and plastic). The quantification of advanced glycation end-products by LC-MS/MS and spectrofluorometry showed an increase in their content with aging. This suggested that the accumulation of such products was correlated to the alterations observed in the mechanical and molecular properties of RTTFs. Analysis of the morphological properties of RTTFs by SHG combined with CT-FIRE software revealed an increase in length and straightness of collagen fibers, whereas their width and wavy fraction decreased. Our integrated study model could be useful to provide additional translational information to monitor progression of diseases related to collagen remodeling in musculoskeletal disorders. Statement of significance Type I collagen is the major component of the extracellular matrix. Its architectural and structural organization plays an important role in the mechanical properties of many tissues at the physiological and pathological levels. The objective of this work is to develop an integrated approach to bring a new insight on the impact of chronological aging on the structural organization and mechanical properties of type I collagen. We combined a portable Raman spectrometer with a mechanical tensile testing device in order to monitor in real time the changes in the Raman fingerprint of type I collagen fibers during the mechanical stress. Raman spectroscopy allowed the identification of the type I collagen bonds that were affected by mechanical stress in a differential manner with aging. (C) 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
查看更多>>摘要：Engineered liver organogenesis is not yet a viable therapeutic option, but ectopic liver histogenesis may be possible. Accumulating evidence has suggested that cell-cell interactions and cell-matrix interactions play an important role in determining the properties of engineered hepatic tissue in vitro and in vivo . In the current study, we utilized heparinized decellularized liver scaffolds and bone marrow mesenchymal stromal cell spheroids to fabricate engineered hepatic tissue, which was subsequently implanted into the omentum of Sprague-Dawley rats with or without liver injury. The survival, liver-specific functions, differentiation level and regenerative potential of the implanted hepatocyte-like cells in this ectopic liver system were evaluated, together with the vascularization status and therapeutic potential of the engineered hepatic tissue. We demonstrated that these hepatic grafts could survive and possess hepatocyte specific function in this ectopic liver system but could also efficiently anastomose with host vascular networks. Furthermore, we found that hepatocyte-like cells within grafts expanded more than 9-fold over the course of 4 weeks in immunocompetent rats with injured livers. Immunostaining revealed that these hepatocyte-like cells could self-organize into cord-like structures in vivo . In addition, these hepatic grafts exhibited therapeutic potential in liver injury induced by CCl4. To our knowledge, this is the first report demonstrating the generation of long-term vascularized hepatic parenchyma at ectopic sites based on decellularized liver scaffolds and stem cells. These results provide an economic and feasible method for engineering hepatic tissue from construction to transplantation. This methodology may be applicable in clinical medicine, especially metabolic liver diseases. Statement of significance In this manuscript, we presented an optimized method for the hepatic engineered tissue (HET) from construction to transplantation. The core of this method is utilizing the combination of heparinized decellularized liver scaffolds and stem cell spheroids, which could provide necessary cell-cell and cellextracellular matrix interactions for HET in vitro and in vivo . We proved that these hepatic grafts could possess hepatocyte specific function and exhibit strong proliferative activity in ectopic liver system, but also able to anastomose with the host vascular networks efficiently and be compatible with the host immune system. This methodology may be possible one day to apply in clinical medicine, especially metabolic liver diseases. (C) 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
查看更多>>摘要：Enzymatic digestion of the pancreas during islet isolation is associated with disintegration of the islet basement membrane (IBM) that can cause reduction of functional and morphological islet integrity. At-tempts to re-establish IBM by coating the surface of culture vessels with various IBM proteins (IBMP) have resulted in loss of islet phenotype and function. This study investigated the capability of Collagen -IV, Laminin-521 and Nidogen-1, utilised as single or combined media supplements, to protect human islets cultured in hypoxia. When individually supplemented to media, all IBMP significantly improved islet survival and in-vitro function, finally resulting in as much as a two-fold increase of islet overall survival. In contrast, combin-ing IBMP enhanced the production of chemokines and reactive oxygen species diminishing all positive effects of individually added IBMP. This impact was concentration-dependent and concerned nearly all parameters of islet integrity. Predictive extrapolation of these findings to data from 116 processed human pancreases suggests that more than 90% of suboptimal pancreases could be rescued for clinical islet transplantation increasing the number of transplantable preparations from actual 25 to 40 when adding Nidogen-1 to pretransplant culture. This study suggests that media supplementation with essential IBMP protects human islets from hy-poxia. Amongst those, certain IBMP may be incompatible when combined or applied at higher concen-trations. Statement of significance Pancreatic islet transplantation is a minimally-invasive treatment that can reverse type 1 diabetes in cer-tain patients. It involves infusing of insulin-producing cell-clusters (islets) from donor pancreases. Un-fortunately, islet extraction is associated with damage of the islet basement membrane (IBM) causing reduced islet function and cell death. Attempts to re-establish the IBM by coating the surface of culture vessels with IBM proteins (IBMP) have been unsuccessful. Instead, we dissolved the most relevant IBM components Collagen-IV, Laminin-521 and Nidogen-1 in media routinely used for clinical islet culture and transplantation. We found human islet survival and function was substantially improved by IBMP, particularly Nidogen-1, when exposed to a hypoxic environment as found in vivo . We also investigated IBMP combinations. Our present findings have important clinical implications. (c) 2021 The Authors. Published by Elsevier Ltd on behalf of Acta Materialia Inc. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )
查看更多>>摘要：Percutaneous biopsies (PBs) are the gold standard diagnostic procedures indicated for renal and hepatic disorders. Nevertheless, they can cause hemorrhages and are contraindicated for coagulopathic patients. In this study we designed, fabricated, and evaluated a small intestinal submucosa (SIS) plug to reduce, and potentially cease, bleeding to decrease death risk after percutaneous hepatic and renal biopsies in healthy and coagulopathic in vivo models. First, the plug's blocking capacity was determined with an increase in its diameter of 24 +/- 11% after immersion in human blood, and the capacity to induce clotting on its surface. The plug's in vivo performance was evaluated in a healthy porcine model, which showed minimal inflammatory reaction without side effects confirmed by histological results after 30 days. The plug's response in the coagulopathic model was assessed using heparinized swine for 2 days, which revealed localized microhemorrhages and mild inflammatory response without any lesions to the surrounding tissue. No major adverse events nor macroscopic hemorrhages were detected in the animal models. Furthermore, we assessed the plug's efficacy to reduce and stop bleeding using a transplant discarded human liver model ( n = 14). In this case, the mass of blood lost was 43.8 +/- 21.8% lower in plugged transplant-discarded human liver biopsies compared to control biopsies without a plug. The bleeding was stopped within three minutes in 92% of plugged cases, but only in 8% of non-plugged cases. We demonstrated the feasibility of making a hemostatic SIS plug, which does not induce major inflammatory reaction and can effectively reduce and stop bleeding after PBs in non-coagulopathic and coagulopathic in vivo models, and in a transplant-discarded human liver model. Statement of significance Percutaneous biopsy (PB) is a gold standard diagnostic procedure, but it can provoke life-threatening complications and is contraindicated for patients with coagulopathic disorders. This study demonstrates that small intestinal submucosa (SIS) can be manufactured into a biocompatible thrombogenic plug, insertable through a commercial Tru-Cut needle sheath. This device takes advantage of the collagen-rich composition of SIS to stop and reduce bleeding more effectively than the traditional PB, indicating that it could be routinely employed in a traditional biopsy to increase safety, or as a cost and time-reducing alternative to transjugular biopsy for coagulopathic patients. (c) 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
查看更多>>摘要：Although there are many hemostatic agents available for use on the battlefield, uncontrolled hemorrhage is still the primary cause of preventable death. Current hemostatic dressings include QuikClot (R) Combat Gauze (QCCG) and XStat (R), which have inadequate success in reducing mortality. To address this need, a new hemostatic material was developed using shape memory polymer (SMP) foams, which demonstrate biocompatibility, rapid clotting, and shape recovery to fill the wound site. SMP foam hemostatic efficacy was examined in a lethal, noncompressible porcine liver injury model over 6 h following injury. Wounds were packed with SMP foams, XStat, or QCCG and compared in terms of time to bleeding cessation, total blood loss, and animal survival. The hemostatic material properties and in vitro blood interactions were also characterized. SMP foams decreased blood loss and active bleeding time in comparison with XStat and QCCG. Most importantly, SMP foams increased the 6 h survival rate by 50% and 37% (vs. XStat and QCCG, respectively) with significant increases in survival times. Based upon in vitro characterizations, this result is attributed to the low stiffness and shape filling capabilities of SMP foams. This study demonstrates that SMP foams have promise for improving upon current clinically available hemostatic dressings and that hemostatic material properties are important to consider in designing devices for noncompressible bleeding control. Statement of significance Uncontrolled hemorrhage is the leading cause of preventable death on the battlefield, and it accounts for approximately 1.5 million deaths each year. New biomaterials are required for improved hemorrhage control, particularly in noncompressible wounds in the torso. Here, we compared shape memory polymer (SMP) foams with two clinical dressings, QuikClot Combat Gauze and XStat, in a pig model of lethal liver injury. SMP foam treatment reduced bleeding times and blood loss and significantly improved animal survival. After further material characterization, we determined that the improved outcomes with SMP foams are likely due to their low stiffness and controlled shape change after implantation, which enabled their delivery to the liver injuries without inducing further wound tearing. Overall, SMP foams provide a promising option for hemorrhage control. (c) 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
查看更多>>摘要：Recent advances in drug delivery have made it possible to release bioactive agents from neural implants specifically to local tissues. Conducting polymer coatings have been explored as a delivery platform in bioelectronics, however, their utility is restricted by their limited loading capacity and stability. This study presents the fabrication of a stable conducting polymer hydrogel (CPH), comprising the hydrogel gelatin methacrylate (GelMA), and conducting polymer polypyrrole (PPy) for the electrically controlled delivery of glutamate (Glu). The hybrid GelMA/PPy/Glu can be photolithographically patterned and covalently bonded to an electrode. Fourier-transform infrared (FTIR) analysis confirmed the interpenetrating nature of PPy through the GelMA hydrogels. Electrochemical polymerisation of PPy/Glu through the GelMA hydrogels resulted in a significant increase in the charge storage capacity as determined by cyclic voltammetry (CV). Long-term electrochemical and mechanical stability was demonstrated over 10 0 0 CV cycles and extracts of the materials were cytocompatible with SH-SY5Y neuroblastoma cell lines. Release of Glu from the CPH was responsive to electrical stimulation with almost five times the amount of Glu released upon constant reduction (-0.6 V) compared to when no stimulus was applied. Notably, GelMA/PPy/Glu was able to deliver almost 14 times higher amounts of Glu compared to conventional PPy/Glu films. The described CPH coatings are well suited in implantable drug delivery applications and compared to conducting polymer films can deliver higher quantities of drug in response to mild electrical stimulus. Statement of significance Conducting polymer hydrogels (CPH) have been explored for the electrically controlled release of bioactives from implantable devices. Typically, the conducting polymer component does not fully penetrate the hydrogel. We report, for the first time, a completely interpenetrating CPH allowing for the full benefits of the composite material to be realised, the hydrogels provide a reservoir for drug delivery, and conducting polymer renders the material responsive to electrical stimulation for drug release. We report a CPH for the electrically controlled delivery of glutamate (excitatory neurotransmitter) where several-fold more glutamate can be delivered compared to conducting polymer films. The described CPH coatings are well suited for use in bioelectronic devices to deliver large quantities of drug in response to mild electrical stimulus. (c) 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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