Showing papers in "ACS Biomaterials Science & Engineering in 2020"
TL;DR: Alginate was used as the printing biomaterial to mimic the elastic modulus of cardiac tissue and proved to create mechanically tunable and suturable models, demonstrating that large-scale 3D bioprinting of soft hydrogels is possible using FRESH and that cardiac tissue constructs can be produced with potential future applications in surgical training and planning.
Abstract: Recent advances in embedded three-dimensional (3D) bioprinting have expanded the design space for fabricating geometrically complex tissue scaffolds using hydrogels with mechanical properties comparable to native tissues and organs in the human body. The advantage of approaches such as Freeform Reversible Embedding of Suspended Hydrogels (FRESH) printing is the ability to embed soft biomaterials in a thermoreversible support bath at sizes ranging from a few millimeters to centimeters. In this study, we were able to expand this printable size range by FRESH bioprinting a full-size model of an adult human heart from patient-derived magnetic resonance imaging (MRI) data sets. We used alginate as the printing biomaterial to mimic the elastic modulus of cardiac tissue. In addition to achieving high print fidelity on a low-cost printer platform, FRESH-printed alginate proved to create mechanically tunable and suturable models. This demonstrates that large-scale 3D bioprinting of soft hydrogels is possible using FRESH and that cardiac tissue constructs can be produced with potential future applications in surgical training and planning.
140 citations
TL;DR: This Review presents a summary of the proposed mechanisms responsible for the initial burst release of the drug from PLGA particles and the known factors affecting the burst release process.
Abstract: Poly(lactic-co-glycolic acid) (PLGA) is the most prevalent polymer drug delivery vehicle in use today. There are about 20 commercialized drug products in which PLGA is used as an excipient. In more than half of these formulations, PLGA is used in the form of microparticles (with sizes in the range between 60 nm and 100 μm). The primary role of PLGA is to control the kinetics of drug release toward achieving sustained release of the drug. Unfortunately, most drug-loaded PLGA microparticles exhibit a common drawback: an initial uncontrolled burst of the drug. After 30 years of utilization of PLGA in controlled drug delivery systems, this initial burst drug release still remains an unresolved challenge. In this Review, we present a summary of the proposed mechanisms responsible for this phenomenon and the known factors affecting the burst release process. Also, we discuss examples of recent efforts made to reduce the initial burst release of the drug from PLGA particles.
131 citations
TL;DR: The study suggests that nCeO2 incorporated PHBV membranes have strong potential to be used as wound dressings to enhance cell proliferation and vascularization and promote the healing of diabetic wounds.
Abstract: Insufficient cell proliferation, cell migration, and angiogenesis are among the major causes for nonhealing of chronic diabetic wounds. Incorporation of cerium oxide nanoparticles (nCeO2) in wound ...
118 citations
TL;DR: This review covers different important aspects of skin-patchable sensors including mechanical strength and flexibility, sensitivity, transparency, self-healing,self-cleaning, and self-powering ability as well as their latest applications in medical technology.
Abstract: Health care monitoring is an extremely important aspect of human life that can be accomplished using wearable skin-patchable sensors. Upon interfacing with the skin or epidermal surface of the body, the sensing patches can monitor the movements of human parts such joints, legs, and fingers as well as tiny vibrations caused by respiration, blood flow, and heart beat. Wearable skin patches have shown improved promise in monitoring the body temperature and fever in addition to quick measurement of blood pressure and pulse rate along with breathing rate. Sensors can also analyze the sweat contents when in contact with the skin as well as other analytes such as diabetes-based volatile organic compounds (VOCs) and organophosphate nerve stimulating agents. Hence, the sensors can be of immense help in the early prediction of malfunctions of the body organs such as heart and lungs, leading to timely and effective treatment. This review covers different important aspects of skin-patchable sensors including mechanical strength and flexibility, sensitivity, transparency, self-healing, self-cleaning, and self-powering ability as well as their latest applications in medical technology.
95 citations
TL;DR: The present work signifies the current advance in the rational design of N, S, and P-co-doped CQDs as highly active peroxidase mimics for novel applications in diverse fields, including catalysis, medical diagnostics, environmental chemistry, and biotechnology.
Abstract: Nanozymes have drawn significant scientific interest due to their high practical importance in terms of overcoming the instability, complicated synthesis, and high cost of protein enzymes. However, their activity is generally limited to particular pHs, especially acidic ones. Herein, we report that luminescent N, S, and P-co-doped carbon quantum dots (NSP-CQDs) act as attractive peroxidase mimetics in a wide pH range, even at neutral pH, for the peroxidase substrate 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) in the presence of H2O2. The synergistic effects of multiple heteroatoms doping in CQDs boost the catalytic activity in a wide pH range attributed to the presence of high density of active sites for enzymatic-like catalysis and accelerated electron transfer during the peroxidase-like reactions. A possible reaction mechanism for the peroxidase-like activity of CQDs is investigated based on the radical trapping experiments. Moreover, the multifunctional activity of NSP-CQDs was further utilized for antibacterial assays for both Gram-negative and Gram-positive model species, including Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), respectively. The growths of the employed E. coli and S. aureus were found to be significantly inhibited due to the peroxidase-mediated perturbation of cell walls. The present work signifies the current advance in the rational design of N, S, and P-co-doped CQDs as highly active peroxidase mimics for novel applications in diverse fields, including catalysis, medical diagnostics, environmental chemistry, and biotechnology.
84 citations
TL;DR: In this article, the authors used a wet etching technique to fabricate 23 nm wide nanostructures randomly aligned as ridges on aluminum (Al) 6063 alloy surfaces.
Abstract: With the rise of bacterial and viral infections including the recent outbreak of coronavirus, the requirement for novel antimicrobial strategies is also rising with urgency. To solve this problem, we have used a wet etching technique to fabricate 23 nm wide nanostructures randomly aligned as ridges on aluminum (Al) 6063 alloy surfaces. The surfaces were etched for 0.5, 1, and 3 h. The surfaces were characterized using scanning electron microscopy, energy-dispersive X-ray spectroscopy, contact angle goniometry, nanoindentation and atomic force microscopy. Strains of the Gram negative bacteria Pseudomonas aeruginosa and the Gram positive bacteria Staphylococcus aureus were used to evaluate the bacterial attachment behavior. For the first time, common respiratory viruses, respiratory syncytial virus (RSV) and rhinovirus (RV), were investigated for antiviral activity on nanostructured surfaces. It was found that the etched Al surfaces were hydrophilic and the nanoscale roughness enhanced with the etching time with Rrms ranging from 69.9 to 995 nm. Both bacterial cells of P. aeruginosa and S. aureus were physically deformed and were nonviable upon attachment after 3 h on the etched Al 6063 surface. This nanoscale surface topography inactivated 92 and 87% of the attached P. aeruginosa and S. aureus cells, respectively. The recovery of infectious RSV was also reduced significantly within 2 h of exposure to the nanostructured surfaces compared to the smooth Al control surfaces. There was a 3-4 log10 reduction in the viability counts of rhinovirus after 24 h on the nanostructured surfaces. The nanostructured surfaces exhibited excellent durability as the surfaces sustained 1000 cycles of 2000 μN load without any damage. This is the first report that has shown the combined antibacterial and antiviral property of the nanostructured surface with excellent nanomechanical properties that could be potentially significant for use in hospital environments to stop the spread of infections arising from physical surfaces.
82 citations
TL;DR: This review focuses on skin structure, the dynamic process of wound healing in injured skin, and existing wound care approaches and the active role of bioactive glasses in wound repair and regeneration.
Abstract: The morbidity, mortality, and burden of burn victims and patients with severe diabetic wounds are still high, which leads to an extensively growing demand for novel treatments with high clinical efficacy. Biomaterial-based wound treatment approaches have progressed over time from simple cotton wool dressings to advanced skin substitutes containing cells and growth factors; however, no wound care approach is yet completely satisfying. Bioactive glasses are materials with potential in many areas that exhibit unique features in biomedical applications. Today, bioactive glasses are not only amorphous solid structures that can be used as a substitute in hard tissue but also are promising materials for soft tissue regeneration and wound healing applications. Biologically active elements such as Ag, B, Ca, Ce, Co, Cu, Ga, Mg, Se, Sr, and Zn can be incorporated in glass networks; hence, the superiority of these multifunctional materials over current materials results from their ability to release multiple therapeutic ions in the wound environment, which target different stages of the wound healing process. Bioactive glasses and their dissolution products have high potency for inducing angiogenesis and exerting several biological impacts on cell functions, which are involved in wound healing and some other features that are valuable in wound healing applications, namely hemostatic and antibacterial properties. In this review, we focus on skin structure, the dynamic process of wound healing in injured skin, and existing wound care approaches. The basic concepts of bioactive glasses are reviewed to better understand the relationship between glass structure and its properties. We illustrate the active role of bioactive glasses in wound repair and regeneration. Finally, research studies that have used bioactive glasses in wound healing applications are summarized and the future trends in this field are elaborated.
81 citations
TL;DR: It is successfully revealed that human umbilical cord mesenchymal stem cells-derived exosomes could effectively promote the proliferation, migration, and osteogenic differentiation of a murine calvariae preosteoblast cell line in vitro.
Abstract: The treatment of bone defects has plagued clinicians. Exosomes, the naturally secreted nanovesicles by cells, exhibit great potential in bone defect regeneration to realize cell-free therapy. In this work, we successfully revealed that human umbilical cord mesenchymal stem cells-derived exosomes could effectively promote the proliferation, migration, and osteogenic differentiation of a murine calvariae preosteoblast cell line in vitro. Considering the long period of bone regeneration, to effectively exert the reparative effect of exosomes, we synthesized an injectable hydroxyapatite (HAP)-embedded in situ cross-linked hyaluronic acid-alginate (HA-ALG) hydrogel system to durably retain exosomes at the defect sites. Then, we combined the exosomes with the HAP-embedded in situ cross-linked HA-ALG hydrogel system to repair bone defects in rats in vivo. The results showed that the combination of exosomes and composite hydrogel could significantly enhance bone regeneration. Our experiment provides a new strategy for exosome-based therapy, which shows great potential in future tissue and organ repair.
79 citations
TL;DR: CSLD-PCLM nanofibrous scaffolds may ideally meet the various requirements of the wound healing process and are promising candidates for wound dressings in future clinical applications.
Abstract: Electrospinning-based wound dressings with multifunctional properties, including hemostasis-promoting, antibacterial, drug release, and therapeutic effects, are of great interest in military and civilian trauma healthcare. Herein, we designed lidocaine hydrochloride (LID) and mupirocin-loaded chitosan/polycaprolactone (CSLD-PCLM) scaffolds with multiple functions as wound dressings. Through the dual spinneret electrospinning technique, the scaffolds achieved a nanofiber structure, which enhanced the interfacial interaction between the scaffold and blood cells and showed excellent blood coagulation capacity. In particular, the scaffolds loaded with LID and mupirocin exhibited rapid release of LID and sustained release of mupirocin. The CSLD-PCLM scaffold containing mupirocin exhibited outstanding antibacterial activity. Moreover, the scaffold significantly enhanced the wound healing process with complete re-epithelialization as well as collagen deposition in a full-thickness skin defect model. Thus, CSLD-PCLM nanofibrous scaffolds may ideally meet the various requirements of the wound healing process and are promising candidates for wound dressings in future clinical applications.
69 citations
TL;DR: This work synthesized and characterized a library of nanoparticles with distinct properties ranging from size, shape, stiffness, and composition to investigate and identify the key attributes influencing particle uptake and transport for brain delivery and shows that particle composition yielded the greatest impact on penetration across the BBB.
Abstract: The delivery of therapeutics to the brain in an efficient, noninvasive manner continues to be a major unmet need in the field of drug delivery. One significant impediment to brain delivery results from the existence of the physical yet dynamic blood-brain barrier (BBB). Despite the many, often complex strategies that currently exist to breach the BBB, adequate delivery of effective therapeutics from the bloodstream continues to remain quite low. Nanotechnology has emerged as a promising tool for brain delivery, but little is known about the important particle parameters that influence delivery. Here, we synthesized and characterized a library of nanoparticles with distinct properties ranging from size, shape, stiffness, and composition to investigate and identify the key attributes influencing particle uptake and transport for brain delivery. To accomplish this task, an in vitro human BBB model was developed and validated using human cerebral microvascular endothelial cells (hCMEC/D3). Particle uptake and apparent permeability coefficients (Papp) were then determined for each particle group. To elucidate the roles of different parameters on particle uptake and transport across the BBB, the predominant mechanisms of endocytosis were also investigated. Our results show that particle composition yielded the greatest impact on penetration across the BBB model. This work lays the foundation and provides new insights into the role of particle parameters on penetration across the BBB.
68 citations
TL;DR: This is the first report to describe the synthesis, cytotoxicity, and antibacterial effects of alginate hydrogel containing NO donor and AgNPs, which might find important local applications in the combat of bacterial infections.
Abstract: Nitric oxide (NO) and silver nanoparticles (AgNPs) are well-known for their antibacterial activity. In this work, S-nitroso-mercaptosuccinic acid (S-nitroso-MSA), a NO donor, and green tea synthesized AgNPs were individually or simultaneously incorporated into alginate hydrogel for topical antibacterial applications. The obtained hydrogels were characterized and the NO release and diffusion of AgNPs and S-nitroso-MSA from alginate hydrogels were investigated. The hydrogels showed a concentration dependent toxicity toward Vero cells. The potent antibacterial effect of the hydrogels was demonstrated toward Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923, and Streptococcus mutans UA159. Interestingly, the combination of S-nitroso-MSA and AgNPs into alginate hydrogels had a superior antibacterial effect, compared with hydrogels containing S-nitroso-MSA or AgNPs individually. This is the first report to describe the synthesis, cytotoxicity, and antibacterial effects of alginate hydrogel containing NO donor and AgNPs. These hydrogels might find important local applications in the combat of bacterial infections.
TL;DR: The injectability and tissue-adhesion improvement in this study gives a new insight into hemostatic agents, and the multifunctional hydrogels have a great potential in the biomedical application.
Abstract: Chitosan (CS) hydrogels are widely used in wound hemostatic agents due to their superior biocompatibility, biodegradability, and hemostatic effect. However, most of them fail to achieve great hemostatic effect because of poor adhesion to bleeding tissues. Also, the conventional implantation surgery of hemostatic hydrogels to internal bleeding wounds may cause secondary trauma to the human body. In this work, catechol-hydroxybutyl chitosan (HBCS-C) has been designed and prepared by grafting hydroxybutyl groups and catechol groups to the CS backbones. The multifunctional HBCS-C hydrogels are fabricated with the properties of thermosensitivity, injectability, tissue-adhesion, biodegradation, biocompatibility, and wound hemostasis. They exhibit excellent liquid-gel transition at different temperatures, through the changes of hydrophilic-hydrophobic interaction and hydrogen bonds generating from hydroxybutyl groups. By the multiple interactions between catechol groups/amino groups and tissues, the biocompatible hydrogels can strongly adhere on the surface of tissue. To further study, the bleeding rat-liver models are made to evaluate the hemostatic effects. After injecting the hydrogel precursor solution into the rat body, the hydrogels are not only formed in situ within 30 s but are also firmly adhered to the bleeding tissues which shows effective hemostasis. The injectability and tissue-adhesion improvement in this study gives a new insight into hemostatic agents, and the multifunctional hydrogels have a great potential in the biomedical application.
TL;DR: A kind of self-healing hydrogel for wound dressing, composed of COL, CS, and dibenzaldehyde-modified PEG2000 via dynamic imine bonds, and the COL/CS hydrogels showed good thermal stability, injectability, and pH sensitivity and could monitor multiple human motions, especially the facial expression via strain sensitivity.
Abstract: Collagen (COL)-chitosan (CS) composite hydrogels are attracting increasing attention because of their great potential for application as biomaterials. However, conventional COL-CS hydrogels were easily disabled for lack of fully reversible linking in their networks. In this work, we developed a kind of self-healing hydrogel for wound dressing, composed of COL, CS, and dibenzaldehyde-modified PEG2000 via dynamic imine bonds, and the COL/CS hydrogels showed good thermal stability, injectability, and pH sensitivity, ideally promoting wound-healing performance and hemostatic ability. Furthermore, the hydrogel could monitor multiple human motions, especially the facial expression via strain sensitivity. This work offers a new perspective for the biomass-based hydrogels applied in medical field as wound dressing.
TL;DR: The main focus will be placed on summarizing recent advances in self-assembled organic nanomedicine for drug delivery, bioimaging, and cancer phototherapy, followed by highlighting a critical perspective on further development of self- assembled organic nanomaterials for future clinical translation.
Abstract: Over the past few decades, tremendous progress has been made in the development of engineering nanomaterials, which opened new horizons in the field of diagnosis and treatment of various diseases. ...
TL;DR: (Sr,Zn)-HA coating heat-treated at 500 °C showed not only excellent mechanical and biological performance but also enhanced the antibacterial properties, which can offset the cytotoxic effects and enhanced biological performance.
Abstract: Implant-related infections are a major concern in total joint prostheses, occurring up to 3% in operations. In this work, 5% Zn2+ was added in HA to offset bacterial activity and 5% Sr2+ was also incorporated as a binary dopant to reduce the cytotoxic effect of Zn2+. The nanosized HA powder was synthesized by the hydrothermal method and then heat-treated at 600 °C for 4 h. The heat-treated powder was plasma-sprayed on a titanium alloy Ti-6Al-4V substrate. The addition of the dopant did not significantly influence the physical and mechanical properties of the coating. However, the cytocompatibility, antimicrobial, and contact-angle properties statistically enhanced. Moreover, the (Sr,Zn)-HA coating was post-heat treated at 500 and 600 °C for 3 h. X-ray diffraction confirmed that after heat treatment phase purity and crystallinity increased and residual stress decreased. Mechanical stability was evaluated by adhesive bond strength, and the results showed that after heat-treatment bonding strength increased from 26.81 ± 2.93 to 29.84 ± 3.62 and 34.66 ± 2.57 MPa, at 500 and 600 °C, respectively. Similar to the mechanical property, antibacterial activities and biological functions are also significantly improved. More interestingly, it was also observed that the Zn2+ ions released from the coating depend on Ca2+, P, and Sr2+ ions while Ca2+, P, and Sr2+ ions relied on heat treatment temperatures. However, (Sr,Zn)-HA coating at 600 °C demonstrates cytotoxic effects on MC3T3-E1 cells, characterized by poor cellular morphology on the coating surface and ultimately, cell death. The doping of Sr2+ with Zn2+, therefore, can offset the cytotoxic effects and enhanced biological performance. All of the outcomes of this study signify that (Sr,Zn)-HA coating heat-treated at 500 °C showed not only excellent mechanical and biological performance but also enhanced the antibacterial properties.
TL;DR: The current status of 2D nanomaterials in breast cancer diagnosis and therapy is reviewed and there is the possibility to explore yet novel properties, biological effects, and oncological applications.
Abstract: Breast cancer is the leading cause of cancer-related mortality among women. Early stage diagnosis and treatment of this cancer are crucial to patients' survival. In addition, it is important to avoid severe side effects during the process of conventional treatments (surgery, chemotherapy, hormonal therapy, and targeted therapy) and increase the patients' quality of life. Over the past decade, nanomaterials of all kinds have shown excellent prospects in different aspects of oncology. Among them, two-dimensional (2D) nanomaterials are unique due to their physical and chemical properties. The functional variability of 2D nanomaterials stems from their large specific surface area as well as the diversity of composition, electronic configurations, interlayer forces, surface functionalities, and charges. In this review, the current status of 2D nanomaterials in breast cancer diagnosis and therapy is reviewed. In this respect, sensing of the tumor biomarkers, imaging, therapy, and theranostics are discussed. The ever-growing 2D nanomaterials are building blocks for the development of a myriad of nanotheranostics. Accordingly, there is the possibility to explore yet novel properties, biological effects, and oncological applications.
TL;DR: The formation of probable intra- and interparticle hot spots was attributed to evaporation-induced aggregation and the biomass-capped silver nanoparticles provided antimicrobial activity by inhibiting the growth of Pseudomonas nitroreducens, a biofilm-forming bacterium, and the fungus, Aspergillus unguis.
Abstract: Silver nanocrystals have been successfully fabricated by the bioreduction route using the ethanolic extract of Azadirachta indica (neem) leaves as the reducing and capping agent without solvent interference. The silver nanocrystals were grown in a single-step method, without the influence of external energy or surfactants, and at room temperature. The nanoparticles were prepared from different ratios of silver ions to reducing agent molecules and were characterized by UV-vis spectroscopy and transmission electron microscopy (TEM). The nanoparticles were roughly spherical and polydispersed with diameters of less than 40 nm, as determined with high-resolution transmission electron microscopy (HRTEM). Fast Fourier transform (FFT) analysis and X-ray diffraction (XRD) analysis elucidated the crystalline nature of the nanoparticles. The presence of participating functional groups was determined with Fourier transform infrared (FTIR) spectroscopy. The synthesized silver nanoparticles were analyzed as a potential surface-enhanced Raman spectroscopy (SERS) substrate by incorporating rhodamine B as the Raman reporter molecule. The bioreduction process was monitored through SERS fingerprint, which was evaluated by the change in vibrational energies of metal-ligand bonds. It was possible to detect the SERS spectral pattern of the probe molecules on the Ag nanoparticles without the use of any aggregating agent. Thus, the formation of probable intra- and interparticle hot spots was attributed to evaporation-induced aggregation. Furthermore, stirring and precursor salt concentration influenced the kinetics involved in the fabrication process. The thermal stability of the lyophilized nanoparticles prepared from 0.1 M AgNO3 was evaluated with thermogravimetric analysis (TGA) and had a residual mass of 60% at 600 °C. X-ray photoelectron spectroscopy (XPS) studies were used to validate the compositional and chemical-state information. The biomass-capped silver nanoparticles provided antimicrobial activity by inhibiting the growth of Pseudomonas nitroreducens, a biofilm-forming bacterium, and the fungus, Aspergillus unguis (NII 08123).
TL;DR: The results of transdermal delivery to diabetic rats showed that the microneedle patches displayed an apparent hypoglycemic effect and indicated a sustained release effect and may act as potential delivery systems for the treatment of diabetes.
Abstract: To reduce the pain caused by subcutaneous injections, microneedle patches as the new transdermal drug delivery method are gaining increased attention. In this study, we fabricated a composite insulin-loaded microneedle patch. Silk fibroin, a natural polymer material, was used as the raw material. The tip of the microneedle had good dissolving property and was able to dissolve rapidly to promote the release of insulin. The pedestal had the property of swelling without dissolving and was carrying insulin as a drug store. The insulin carried by the pedestal could release continuously through the micropore channels created by the microneedles. This kind of microneedle could achieve a sustained release effect. It was observed that the insulin had good storage stability in this kind of microneedle, and it maintained more than 90% of its biological activity after 30 days. The results of transdermal delivery to diabetic rats showed that the microneedle patches displayed an apparent hypoglycemic effect and indicated a sustained release effect. These drug-loaded silk microneedle patches may act as potential delivery systems for the treatment of diabetes.
TL;DR: The improved biocompatibility and the ability to support cardiomyocyte development suggest that thin PLA:PGS scaffolds could be promising biomaterials for cardiac application.
Abstract: Many works focus on the use of polyesters such as poly(lactic acid) (PLA) to produce nanofibrous scaffolds for cardiac tissue engineering. However, such scaffolds are hydrophobic and difficult to f...
TL;DR: A review of the recent progress of CDT based on iron-containing nanomaterials, including iron oxide nanoparticles, glassy iron nanoclusters, ferrocene nanoparticles), metal polyphenol networks, metal-organic frameworks, etc, highlighting their potential for precise cancer therapy.
Abstract: Chemodynamic therapy (CDT) has aroused extensive attention for cancer treatment in the last five years, as it could suppress tumor progression through in situ detrimental oxidative stress of the tumor cells via the Fenton reaction. Under a tumor acidic microenvironment, the Fenton reaction can be initiated for disproportioning endogenous hydrogen peroxide into highly toxic hydroxyl radical. Taking advantage of the highly tumor-specific therapy modality, various Fenton nanocatalysts have been developed for CDT. In particular, iron-containing Fenton nanocatalysts with minimal cytotoxicity exhibit great promise for clinical translation. In this review, we summarize the recent progress of CDT based on iron-containing nanomaterials, including iron oxide nanoparticles, glassy iron nanoclusters, ferrocene nanoparticles, metal polyphenol networks, metal-organic frameworks, etc. We also discuss the challenges and perspectives for promoting CDT by rational design of iron-containing nanomaterials, highlighting their potential for precise cancer therapy.
TL;DR: The data demonstrated that macrophage behavior and the further inflammatory response are mechanically regulated by hydrogel stiffness, which can provide new insights into the future design and application of novel hydrogels-based biomaterials.
Abstract: The successful tissue integration of a biomedical material is mainly determined by the inflammatory response after implantation. Macrophage behavior toward implanted materials is pivotal to determine the extent of the inflammatory response. Hydrogels with different properties have been developed for various biomedical applications such as wound dressings or cell-loaded scaffolds. However, there is limited investigation available on the effects of hydrogel mechanical properties on macrophage behavior and the further host inflammatory response. To this end, methacrylate-gelatin (GelMA) hydrogels were selected as a model material to study the effect of hydrogel stiffness (2, 10, and 29 kPa) on macrophage phenotype in vitro and the further host inflammatory response in vivo. Our data showed that macrophages seeded on stiffer surfaces tended to induce macrophages toward a proinflammatory (M1) phenotype with increased macrophage spreading, more defined F-actin and focal adhesion staining, and more proinflammatory cytokine secretion and cluster of differentiation (CD) marker expression compared to those on surfaces with a lower stiffness. When these hydrogels were further subcutaneously implanted in mice to assess their inflammatory response, GelMA hydrogels with a lower stiffness showed more macrophage infiltration but thinner fibrotic capsule formation. The more severe inflammatory response can be attributed to the higher percentage of M1 macrophages induced by GelMA hydrogels with a higher stiffness. Collectively, our data demonstrated that macrophage behavior and the further inflammatory response are mechanically regulated by hydrogel stiffness. The macrophage phenotype rather than the macrophage number predominately determined the inflammatory response after the implantation, which can provide new insights into the future design and application of novel hydrogel-based biomaterials.
TL;DR: This review provides a comprehensive overview of existing Mg-based composite preparation and their mechanical and corrosion properties and biological responses and future perspectives on the development of Mg -based composite biomaterials.
Abstract: Recently, there is a growing interest in developing magnesium (Mg) based degradable biomaterial. Although corrosion is a concern for Mg, other physical properties, such as low density and Young's modulus, combined with good biocompatibility, lead to significant research and development in this area. To address the issues of corrosion and low yield strength of pure Mg, several approaches have been adopted, such as, composite preparation with suitable bioactive reinforcements, alloying, or surface modifications. This review specifically focuses on recent developments in Mg-based metal matrix composites (MMCs) for biomedical applications. Much effort has gone into finding suitable bioactive, bioresorbable reinforcements and processing techniques that can improve upon existing materials. In summary, this review provides a comprehensive overview of existing Mg-based composite preparation and their mechanical and corrosion properties and biological responses and future perspectives on the development of Mg-based composite biomaterials.
TL;DR: GNC hydrogel could act as an ideal pH-monitoring and oral drug delivery system in near-neutral pH at the same time and could be useful for quantitative pH measurement.
Abstract: Delivery of therapeutics to the intestinal region bypassing the harsh acidic environment of the stomach has long been a research focus. On the other hand, monitoring a system's pH during drug delivery is a crucial diagnosis factor as the activity and release rate of many therapeutics depend on it. This study answered both of these issues by fabricating a novel nanocomposite hydrogel for intestinal drug delivery and near-neutral pH sensing at the same time. Gelatin nanocomposites (GNCs) with varying concentrations of carbon dots (CDs) were fabricated through simple solvent casting methods. Here, CDs served a dual role and simultaneously acted as a cross-linker and chromophore, which reduced the usage of toxic cross-linkers. The proposed GNC hydrogel sample acted as an excellent pH sensor in the near-neutral pH range and could be useful for quantitative pH measurement. A model antibacterial drug (cefadroxil) was used for the in vitro drug release study at gastric pH (1.2) and intestinal pH (7.4) conditions. A moderate and sustained drug release profile was noticed at pH 7.4 in comparison to the acidic medium over a 24 h study. The drug release profile revealed that the pH of the release medium and the percentage of CDs cross-linking influenced the drug release rate. Release data were compared with different empirical equations for the evaluation of drug release kinetics and found good agreement with the Higuchi model. The antibacterial activity of cefadroxil was assessed by the broth microdilution method and found to be retained and not hindered by the drug entrapment procedure. The cell viability assay showed that all of the hydrogel samples, including the drug-loaded GNC hydrogel, offered acceptable cytocompatibility and nontoxicity. All of these observations illustrated that GNC hydrogel could act as an ideal pH-monitoring and oral drug delivery system in near-neutral pH at the same time.
TL;DR: This work summarizes the recent advances in the area of DNA hydrogels where these are used either as structural material or as functional entities to make hybrid constructs with various biomedical applications.
Abstract: DNA-based nanostructures have emerged as a versatile component for nanoscale construction of soft materials. Multiple structural, functional properties and versatility in conjugation with other biomolecules made DNA the material of choice to use in various biomedical applications. DNA-based hydrogels significantly attracted attention in recent years owing to their properties and applications in biosensing, bioimaging, and therapeutics. Here, we summarize the recent advances in the area of DNA hydrogels where these are used either as structural material or as functional entities to make hybrid constructs with various biomedical applications. Multiple synthetic routes for constructing DNA hydrogels are summarized first, where the structural motifs and spatial arrangements are considered for the classification of DNA materials. We then present the characterization and properties of DNA hydrogels using multiple imaging and biophysical techniques. Further, different biomedical applications of DNA hydrogels are presented such as biosensing, bioimaging, and targeted drug delivery and as scaffolds to program cellular systems. Last, we discuss the vision and potential of DNA based hydrogels as an emerging class of therapeutically important devices for theragnostic and other biological applications.
TL;DR: A mouse model of melanoma tumor has been established to evaluate the synergistic effect of two-stage separable MN phototherapy and chemotherapy in the treatment of skin cancer.
Abstract: It is extremely important to develop a minimally invasive and efficient approach for treatment of superficial skin tumors (SSTs). In this work, a near-infrared (NIR)-triggered transdermal therapeutic system based on two-stage separable microneedles (MNs) has been proposed for synergistic chemo-photothermal therapy against SSTs. Lauric acid and polycaprolactone as phase-change materials have been used to prepare the arrowheads of the two-stage separable MNs in which an anticancer drug (doxorubicin, DOX) and photothermal agent (indocyanine green, ICG) were embedded. The arrowheads are capped on the dissolvable support bases that consisted of poly(vinyl alcohol)/polyvinyl pyrrolidone (PVA/PVP). After inserting into skin tissue, the PVA/PVP support bases can be dissolved quickly owing to the absorption of the interstitial fluid, leading the arrowheads to be left in the skin tissue. Under NIR irradiation, the arrowheads embedded in the skin can be ablated because of the photothermal conversion of the ICG, resulting in liberation and penetration of the DOX from the MNs into the tumor tissue. A mouse model of melanoma tumor has been established to evaluate the synergistic effect of two-stage separable MN phototherapy and chemotherapy in the treatment of skin cancer.
TL;DR: The ability of the nanostructured aluminum Al 6063 alloy surfaces to inactivate the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is reported.
Abstract: In this letter, we report the ability of the nanostructured aluminum Al 6063 alloy surfaces to inactivate the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There was no recoverable viable virus after 6 h of exposure to the nanostructured surface, elucidating a 5-log reduction compared to a flat Al 6063 surface. The nanostructured surfaces were fabricated using wet-etching techniques which generated nanotextured, randomly aligned ridges approximately 23 nm wide on the Al 6063 alloy surfaces. In addition to the excellent mechanical resilience properties previously shown, the etched surfaces have also demonstrated superior corrosion resistance compared to the control surfaces. Such nanostructured surfaces have the potential to be used in healthcare environment such as hospitals and public spaces to reduce the surface transmission of SARS-CoV-2 and combat COVID-19.
TL;DR: Results implied that delivery of RS loaded cationic liposomes substantially controlled the severity of HCC and that they can be considered as a promising nanocarrier in the management of H CC.
Abstract: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. The destructive nature of the disease makes it difficult for clinicians to manage the condition. Hence...
TL;DR: A sandwich-type electrochemical immunosensor designed to determine NSE sensitively exhibited a low detection limit and broad linear range, implying that the presented method had great application potential in clinical bioanalysis.
Abstract: Medically, neuron-specific enolase (NSE) as a specific tumor marker has become an important indicator to diagnose small-cell lung carcinoma. In this study, a sandwich-type electrochemical immunosensor was designed to determine NSE sensitively. Au nanoparticle (Au NP)-embedded zinc-based metal-organic frameworks (Au@MOFs) were prepared as the substrate materials to modify the electrode and immobilize the primary antibody (Ab1). The Au@MOFs with the free amino groups on the MOF surface could effectively increase the immobilization amount of Ab1 through covalent linkage. Simultaneously, the embedding of Au NPs improved the conductivity of MOFs and accelerated interface electron transfer. Sub-30 nm trimetallic Au@Pd^Pt nanocubes (Au@Pd^Pt NCs) loaded onto ultrathin MnO2 nanosheets (MnO2 UNs/Au@Pd^Pt NCs) acted as the labels of secondary antibodies. The small-size Au@Pd^Pt NCs enhanced atomic utilization efficiency and offered more catalytic active sites. The MnO2 UNs with high external surface areas could improve the dispersion of Au@Pd^Pt NCs. The MnO2 UNs/Au@Pd^Pt NCs could catalyze the H2O2 reduction and promote the oxidation of hydroquinone to quinone effectively because of their synergistic effect; thus, the generated quinone achieved amplification of the highly reductive peak current. Furthermore, under the optimal conditions, the immunosensor exhibited a low detection limit (4.17 fg/mL) and broad linear range (10 fg/mL to 100 ng/mL). The results were satisfactory for NSE detection in human serum samples, implying that the presented method had great application potential in clinical bioanalysis.
TL;DR: In vitro and in vivo experiments demonstrated the excellent cancer therapy effect with low side effects of the carriers and it is expected that dual-sensitive DOX@HMSN-SS-PLL(cit) could play an important role in cancer therapy.
Abstract: The purpose of developing novel anticancer drug delivery systems (DDSs) is to efficiently carry and release drugs into cancer cells and minimize side effects. In this work, based on hollow mesoporous silica nanoparticle (HMSN) and the charge-reversal property, a pH/GSH-dual-sensitive DDS named DOX@HMSN-SS-PLL(cit) was reported. HMSN encapsulated DOX with high efficacy and was then covered by the "gatekeeper" β-cyclodextrin (β-CD) through the glutathione (GSH)-sensitive disulfide bond. Thereafter, adamantine-blocked citraconic-anhydride-functionalized poly-l-lysine (PLL(cit)-Ad) was decorated on the surface of the particles via host-guest interaction. The negatively charged carriers were stable in the neutral environment in vivo and could be effectively transported to the tumor site. The surface charge of the nanoparticles could be reversed in the weakly acidic environment, which increased the cellular uptake ability of the carriers by the cancer cells. After cellular internalization, β-CD can be removed by breakage of the disulfide bond in the presence of a high concentration of GSH, leading to DOX release. The preparation process of the carriers was monitored. The charge-reversal capability and the controlled drug-release behavior of the carriers were also investigated. In vitro and in vivo experiments demonstrated the excellent cancer therapy effect with low side effects of the carriers. It is expected that dual-sensitive DOX@HMSN-SS-PLL(cit) could play an important role in cancer therapy.
TL;DR: The present study provided an optimized formula to fabricate osteoinductive calcium phosphate (CaP) ceramics with high precision and controllable three-dimensional (3D) structure that could have good potential in customized bone-repairing applications.
Abstract: Digital light processing (DLP) is one of the additive manufacturing (AM) technologies suitable for preparation of high-performance ceramics. The present study provided an optimized formula to fabricate osteoinductive calcium phosphate (CaP) ceramics with high precision and controllable three-dimensional (3D) structure. Among the four surfactants, monoalcohol ethoxylate phosphate was the best one to modify the CaP powders for preparing the photocurable slurry with high solid loading and good spreading ability. By testing the photopolymerization property of the 60 wt % solid loading slurry, the appropriate processing parameters including the slice thickness (50 μm), exposure intensity (10.14 mW/cm2), and exposure time (8 s) were set to perform the 3D printing of the ceramic green body in the DLP system. After the debinding and sintering, the final CaP ceramics were acquired. The stereomicroscope and SEM observation confirmed the high precision of the ceramics. The average compressive strength of the ceramics with 64.5% porosity reached 9.03 MPa. On only soaking in simulated body fluid for 1 day, an even layer of apatite formed on the ceramic surface. The cell culture confirmed that the ceramics could allow the good attachment, growth, and proliferation of murine bone marrow mesenchymal stem cells. After implantation into the dorsal muscles of beagle dogs for 3 months, abundant blood vessels and obvious ectopic bone formation were observed clearly by the histological evaluation. Therefore, with good bioactivity and osteoinductivity as well as high precision and adjustable mechanical strength, the 3D printed CaP ceramics in the DLP system could have good potential in customized bone-repairing applications.