Showing papers in "Materials today bio in 2022"
TL;DR: In this paper , a review of different types of smart/stimuli-responsive hydrogels with emphasis on their synthesis scheme is presented, and the mechanisms of their responsiveness to different stimuli are elaborated.
Abstract: Recently, biomedicine and tissue regeneration have emerged as great advances that impacted the spectrum of healthcare. This left the door open for further improvement of their applications to revitalize the impaired tissues. Hence, restoring their functions. The implementation of therapeutic protocols that merge biomimetic scaffolds, bioactive molecules, and cells plays a pivotal role in this track. Smart/stimuli-responsive hydrogels are remarkable three-dimensional (3D) bioscaffolds intended for tissue engineering and other biomedical purposes. They can simulate the physicochemical, mechanical, and biological characters of the innate tissues. Also, they provide the aqueous conditions for cell growth, support 3D conformation, provide mechanical stability for the cells, and serve as potent delivery matrices for bioactive molecules. Many natural and artificial polymers were broadly utilized to design these intelligent platforms with novel advanced characteristics and tailored functionalities that fit such applications. In the present review, we highlighted the different types of smart/stimuli-responsive hydrogels with emphasis on their synthesis scheme. Besides, the mechanisms of their responsiveness to different stimuli were elaborated. Their potential for tissue engineering applications was discussed. Furthermore, their exploitation in other biomedical applications as targeted drug delivery, smart biosensors, actuators, 3D and 4D printing, and 3D cell culture were outlined. In addition, we threw light on smart self-healing hydrogels and their applications in biomedicine. Eventually, we presented their future perceptions in biomedical and tissue regeneration applications. Conclusively, current progress in the design of smart/stimuli-responsive hydrogels enhances their prospective to function as intelligent, and sophisticated systems in different biomedical applications.
72 citations
TL;DR: In this paper , an integrated electrospinning system consisting of one nanoyarn-forming unit and one hot stretching unit is reported to fabricate silk fibroin (SF)/poly (L-lactic acid) (PLLA) nanofibrous yarns (nanoyarns).
Abstract: Bio-textiles have aroused attractive attentions in tissue engineering and regenerative medicine, and developing robust, bio-absorbable, and extracellular matrix (ECM) fibril-mimicking nanofibrous textiles is urgently required for the renewal of existing microfibrous textile-based scaffolds and grafts. In this study, an integrated electrospinning system consisting of one nanoyarn-forming unit and one hot stretching unit is reported to fabricate silk fibroin (SF)/poly (L-lactic-acid) (PLLA) nanofibrous yarns (nanoyarns). The hot stretching process is demonstrated to significantly improve the fiber alignment, crystallinity, and mechanical properties of SF/PLLA nanoyarns, compared to the unstretched controls. For instance, the fiber alignment degree of hot stretched 50/50 SF/PLLA nanoyarn has increased by 25%, and the failure strength has increased by 246.5%, compared with the corresponding un-stretched control. Increasing the SF/PLLA mass ratio is found to significantly decrease the crystallinity and mechanical properties, but notably increase the degradation rate and surface hydrophilicity of SF/PLLA nanoyarns. Different SF/PLLA nanoyarns are further meticulously interwoven with warp and weft directions to obtain several nanofibrous woven textiles. The results from in vitro cell characterization and in vivo subcutaneous implantation show that increasing the SF/PLLA mass ratio significantly improves the biological properties and effectively reduces the inflammatory response of nanoyarn-constructed textiles. Overall, this study demonstrates that our SF/PLLA nanoyarns with controllable physical, mechanical and biological performances are fantastic candidates for the designing and development of advanced nanoarchitectured textile tissue scaffolds.
68 citations
TL;DR: In this article , a review summarizes the advanced applications of triggerable nanomaterials dependent on various internal stimuli and external stimuli (including temperature, ultrasound (US), magnetic, photo, voltage, and mechanical friction).
Abstract: Inflammatory arthritis is a major cause of disability in the elderly. This condition causes joint pain, loss of function, and deterioration of quality of life, mainly due to osteoarthritis (OA) and rheumatoid arthritis (RA). Currently, available treatment options for inflammatory arthritis include anti-inflammatory medications administered via oral, topical, or intra-articular routes, surgery, and physical rehabilitation. Novel alternative approaches to managing inflammatory arthritis, so far, remain the grand challenge owing to catastrophic financial burden and insignificant therapeutic benefit. In the view of non-targeted systemic cytotoxicity and limited bioavailability of drug therapies, a major concern is to establish stimuli-responsive drug delivery systems using nanomaterials with on-off switching potential for biomedical applications. This review summarizes the advanced applications of triggerable nanomaterials dependent on various internal stimuli (including reduction-oxidation (redox), pH, and enzymes) and external stimuli (including temperature, ultrasound (US), magnetic, photo, voltage, and mechanical friction). The review also explores the progress and challenges with the use of stimuli-responsive nanomaterials to manage inflammatory arthritis based on pathological changes, including cartilage degeneration, synovitis, and subchondral bone destruction. Exposure to appropriate stimuli induced by such histopathological alterations can trigger the release of therapeutic medications, imperative in the joint-targeted treatment of inflammatory arthritis.
60 citations
TL;DR: In this paper , the potential and challenges in the future development of photothermal-enhanced Fenton-based nanocatalytic tumor therapy for clinical application are discussed, and a comprehensive review on this subject is presented.
Abstract: Photothermal (PT)-enhanced Fenton-based chemodynamic therapy (CDT) has attracted a significant amount of research attention over the last five years as a highly effective, safe, and tumor-specific nanomedicine-based therapy. CDT is a new emerging nanocatalyst-based therapeutic strategy for the in situ treatment of tumors via the Fenton reaction or Fenton-like reaction, which has got fast progress in recent years because of its high specificity and activation by endogenous substances. A variety of multifunctional nanomaterials such as metal-, metal oxide-, and metal-sulfide-based nanocatalysts have been designed and constructed to trigger the in situ Fenton or Fenton-like reaction within the tumor microenvironment (TME) to generate highly cytotoxic hydroxyl radicals (•OH), which is highly efficient for the killing of tumor cells. However, research is still required to enhance the curative outcomes and minimize its side effects. Specifically, the therapeutic efficiency of certain CDTs is still hindered by the TME, including low levels of endogenous hydrogen peroxide (H2O2), overexpression of reduced glutathione (GSH), and low catalytic efficacy of Fenton or Fenton-like reactions (pH 5.6-6.8), which makes it difficult to completely cure cancer using monotherapy. For this reason, photothermal therapy (PTT) has been utilized in combination with CDT to enhance therapeutic efficacy. More interestingly, tumor heating during PTT not only causes damage to the tumor cells but can also accelerate the generation of •OH via the Fenton and Fenton-like reactions, thus enhancing the CDT efficacy, providing more effective cancer treatment when compared with monotherapy. Currently, synergistic PT-enhanced CDT using multifunctional nanomaterials with both PT and chemodynamic properties has made enormous progress in cancer theranostics. However, there has been no comprehensive review on this subject published to date. In this review, we first summarize the recent progress in PT-enhanced Fenton-based CDT for cancer treatment. We then discuss the potential and challenges in the future development of PT-enhanced Fenton-based nanocatalytic tumor therapy for clinical application.
43 citations
TL;DR: In this article , a review summarizes the advances and technologies in the production and design of cancer nanomedicines to achieve clinical translation and commercialization, highlighting existing challenges and opportunities in the field.
Abstract: Nanotechnology in medical applications, especially in oncology as drug delivery systems, has recently shown promising results. However, although these advances have been promising in the pre-clinical stages, the clinical translation of this technology is challenging. To create drug delivery systems with increased treatment efficacy for clinical translation, the physicochemical characteristics of nanoparticles such as size, shape, elasticity (flexibility/rigidity), surface chemistry, and surface charge can be specified to optimize efficiency for a given application. Consequently, interdisciplinary researchers have focused on producing biocompatible materials, production technologies, or new formulations for efficient loading, and high stability. The effects of design parameters can be studied in vitro, in vivo, or using computational models, with the goal of understanding how they affect nanoparticle biophysics and their interactions with cells. The present review summarizes the advances and technologies in the production and design of cancer nanomedicines to achieve clinical translation and commercialization. We also highlight existing challenges and opportunities in the field.
34 citations
TL;DR: In this article , a polydopamine nanoparticles (PDA NPs) were fabricated by growing Cu NPs in situ on the surface of PDA and then introduced into a polyelectrolyte hydrogel precursor, named as CPAP.
Abstract: Polydopamine nanoparticles (PDA NPs) are an appealing biomimetic photothermal agent for photothermal antibacterial treatment because of their long-term safety, excellent photostability, accessible manufacturing, and good biodegradability. However, the low photothermal conversion efficiency (PCE) of PDA NPs requires high-power and long-term near-infrared light irradiation, which severely restricts their practical application. In this work, PDA@Cu NPs were fabricated by growing Cu NPs in situ on the surface of PDA and then introduced into a polyelectrolyte hydrogel precursor (cationic polyethyleneimine/anionic pectin, named as CPAP). The formulated photothermal platform possessed a high PCE (55.4%), almost twice as much as pure PDA NPs (30.8%). Moreover, the designed CPAP/PDA@Cu captured and killed some bacteria by electrostatic adsorption, which helped enhance the antibacterial performance. As expected, the formed CPAP/PDA@Cu that combined the advantageous features of PDA@Cu NPs (high PCE) and CPAP matrix (inherent antibacterial activity and preventing NPs aggregation) can efficiently kill bacteria both in vitro and in vivo under the help of near-infrared laser irradiation. Taken together, this study offers a promising strategy for constructing a facile and safe PDA-based photothermal agent for photothermal antibacterial therapy.
33 citations
TL;DR: In this paper , the authors systematically summarize the superior functions of various cell membrane camouflaged NPs in tumor imaging, especially highlighting the advanced applications in different imaging techniques, which is to provide the theoretical supports for the development of precise guided imaging and tumor treatment.
Abstract: Nanoparticles (NPs) modified by cell membranes represent an emerging biomimetic platform that can mimic the innate biological functions resulting from the various cell membranes in biological systems. researchers focus on constructing the cell membrane camouflaged NPs using a wide variety of cells, such as red blood cell membranes (RBC), macrophages and cancer cells. Cell membrane camouflaged NPs (CMNPs) inherit the composition of cell membranes, including specific receptors, antigens, proteins, for target delivering to the tumor, escaping immune from clearance, and prolonging the blood circulation time, etc. Combining cell membrane-derived biological functions and the NP cores acted cargo carriers to encapsulate the imaging agents, CMNPs are widely developed to apply in tumor imaging techniques, including computed tomography (CT), magnetic resonance imaging (MRI), fluorescence imaging (FL) and photoacoustic imaging (PA). Herein, in this review, we systematically summarize the superior functions of various CMNPs in tumor imaging, especially highlighting the advanced applications in different imaging techniques, which is to provide the theoretical supports for the development of precise guided imaging and tumor treatment.
29 citations
TL;DR: In this article , a review of the latest developments contributing to our understanding of the mechanisms underlying nanodrugs in the treatment of liver injury via harnessing reactive oxygen/nitrogen species (RONS) and inflammation plays a key role in progression of liver disease.
Abstract: Overall, 12% of the global population (800 million) suffers from liver disease, which causes 2 million deaths every year. Liver injury involving characteristic reactive oxygen/nitrogen species (RONS) and inflammation plays a key role in progression of liver disease. As a key metabolic organ of the human body, the liver is susceptible to injury from various sources, including COVID-19 infection. Owing to unique structural features and functions of the liver, most current antioxidants and anti-inflammatory drugs are limited against liver injury. However, the characteristics of the liver could be utilized in the development of nanodrugs to achieve specific enrichment in the liver and consequently targeted treatment. Nanodrugs have shown significant potential in eliminating RONS and regulating inflammation, presenting an attractive therapeutic tool for liver disease through controlling liver injury. Therefore, the main aim of the current review is to provide a comprehensive summary of the latest developments contributing to our understanding of the mechanisms underlying nanodrugs in the treatment of liver injury via harnessing RONS and inflammation. Meanwhile, the prospects of nanodrugs for liver injury therapy are systematically discussed, which provides a sound platform for novel therapeutic insights and inspiration for design of nanodrugs to treat liver disease.
27 citations
TL;DR: In this article , a series of multifunctional hydrogels (Gel@Zn) were fabricated through free-radical polymerization interaction based on gelatin methacrylate, and then immersed them into zinc nitrate solutions based on the metal coordination and ionic bonding interaction.
Abstract: Gelatin-based hydrogels have a broad range of biomedical fields due to their biocompatibility, convenience for chemical modifications, and degradability. However, gelatin-based hydrogels present poor antibacterial ability that hinders their applications in treating infected wound healing. Herein, a series of multifunctional hydrogels (Gel@Zn) were fabricated through free-radical polymerization interaction based on gelatin methacrylate (GelMA) and dopamine methacrylate (DMA), and then immersed them into zinc nitrate solutions based on the metal coordination and ionic bonding interaction. These designed hydrogels wound dressings show strong antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) by increasing intracellular reactive oxygen species (ROS) level and changing bacterial membrane permeability. Meanwhile, the hydrogels exhibit good cytocompatibility, enhance the adhesion, proliferation, and migration of NIH-3T3 cells. Furthermore, Gel@Zn-0.08 (0.08 M Zn2+ immersed with Gel sample) presents a good balance between antibacterial effect, cell viability, and hemolytic property. Compared with 3 M commercial dressings, Gel@Zn-0.04, and Gel@Zn-0.16, the Gel@Zn-0.08 could significantly improve the healing process of S. aureus-infected full-thickness wounds via restrained the inflammatory responses, enhanced epidermis and granulation tissue information, and stimulated angiogenesis. Our study indicates that the Zn-incorporated hydrogels are promising bioactive materials as wound dressings for infected full-thickness wound healing and skin regeneration.
25 citations
TL;DR: Wang et al. as discussed by the authors summarized hundreds of typical studies on various ingredients, preparation methods, antibacterial mechanisms, and internal antibacterial factors to understand adhesive hydrogels with natural antibacterial agents for wound dressings.
Abstract: The wound healing process is usually susceptible to different bacterial infections due to the complex physiological environment, which significantly impairs wound healing. The topical application of antibiotics is not desirable for wound healing because the excessive use of antibiotics might cause bacteria to develop resistance and even the production of super bacteria, posing significant harm to human well-being. Wound dressings based on adhesive, biocompatible, and multi-functional hydrogels with natural antibacterial agents have been widely recognized as effective wound treatments. Hydrogels, which are three-dimensional (3D) polymer networks cross-linked through physical interactions or covalent bonds, are promising for topical antibacterial applications because of their excellent adhesion, antibacterial properties, and biocompatibility. To further improve the healing performance of hydrogels, various modification methods have been developed with superior biocompatibility, antibacterial activity, mechanical properties, and wound repair capabilities. This review summarizes hundreds of typical studies on various ingredients, preparation methods, antibacterial mechanisms, and internal antibacterial factors to understand adhesive hydrogels with natural antibacterial agents for wound dressings. Additionally, we provide prospects for adhesive and antibacterial hydrogels in biomedical applications and clinical research.
24 citations
TL;DR: Zhang et al. as mentioned in this paper combined the advantages of polycaprolactone (PCL) and Zn by fabricating PCL/Zn composite scaffolds with different Zn powder contents through fused deposition modeling.
Abstract: Polycaprolactone (PCL) is a polymer material suitable for being prepared into porous scaffolds used in bone tissue engineering, however, insufficient osteogenic ability and mechanical strength limit its application. Zinc (Zn) alloy with proper mechanical strength and osteogenesis is a promising biodegradable metal that have attracted much attention. Herein, we combined the advantages of PCL and Zn by fabricating PCL/Zn composite scaffolds with different Zn powder contents (1 wt%, 2 wt%, 3 wt%) through fused deposition modelling. The mechanical property, cytocompatibility and Zn ions release behavior of PCL/Zn scaffolds were analyzed in vitro. The osteogenesis and osteoclastogenesis properties of the scaffolds were evaluated by being implanted into Sprague-Dawley rats calvaria defect. Results showed that the PCL/Zn scaffolds exhibited improved mechanical properties and cytocompatibility compared with the pure PCL scaffolds. At 8 weeks after in vivo implantaion, the addition of Zn powder promoted new bone formation, in a dose-dependent manner. The scaffolds with 2 wt% Zn displayed the best osteogenic effect, while the osteogenic effect was slightly reduced in the scaffolds with 3 wt% Zn. In the studied Zn contents, the PCL/Zn scaffolds gradually promoted osteoclastogenesis with increasd Zn content. In the 3 wt% Zn group, TRAP-positive cells were observed on the newly formed bone edges around the scaffolds. These dose-dependent effects were verified in vitro using MC3T3-E1 and RAW264.7 cells. Finally, we revealed that Zn2+ regulated osteogenesis and osteoclastogenesis by activation of the Wnt/β-catenin and NF-κB signalling pathways, respectively.
TL;DR: In this article , a multi-functional carboxymethyl chitosan/hyaluronic acid-dopamine (CMC/HA-DA) hydrogel was crosslinked by horseradish peroxidase and hydrogen peroxide.
Abstract: Injectable Hydrogels with adhesive, antioxidant and hemostatic properties are highly desired for promoting skin injury repair. In this study, we prepared a multi-functional carboxymethyl chitosan/hyaluronic acid-dopamine (CMC/HA-DA) hydrogel, which can be crosslinked by horseradish peroxidase and hydrogen peroxide. The antioxidation, gelation time, degradability, rheology and antihemorrhagic properties of hydrogels can be finely tuned by varying composition ratio. The cytocompatibility test and hemolysis test confirmed that the designed hydrogel holds good biocompatibility. More importantly, the repair effect of the hydrogel on full-thickness skin injury model in mice was studied. The results of wound healing, collagen deposition, immunohistochemistry and immunofluorescence showed that CMC/HA-DA hydrogel could significantly promote angiogenesis and cell proliferation at the injured site. Notably, the inflammatory response can also be regulated to promote the repair of full-thickness skin defect in mice. Results indicate that this injectable CMC/HA-DA hydrogel holds high application prospect for promising wound healing.
TL;DR: A review of the development of antimicrobial scaffolds against bacteria and fungi using a wide range of materials, including polymers, biopolymers, glass, ceramics and antimicrobials agents such as antibiotics, antiseptics, antimicrobial polymers and peptides, metals, carbon nanomaterials, combinatorial strategies is presented in this article .
Abstract: Due to microbial infections dramatically affect cell survival and increase the risk of implant failure, scaffolds produced with antimicrobial materials are now much more likely to be successful. Multidrug-resistant infections without suitable prevention strategies are increasing at an alarming rate. The ability of cells to organize, develop, differentiate, produce a functioning extracellular matrix (ECM) and create new functional tissue can all be controlled by careful control of the extracellular microenvironment. This review covers the present state of advanced strategies to develop scaffolds with antimicrobial properties for bone, oral tissue, skin, muscle, nerve, trachea, cardiac and other tissue engineering applications. The review focuses on the development of antimicrobial scaffolds against bacteria and fungi using a wide range of materials, including polymers, biopolymers, glass, ceramics and antimicrobials agents such as antibiotics, antiseptics, antimicrobial polymers, peptides, metals, carbon nanomaterials, combinatorial strategies, and includes discussions on the antimicrobial mechanisms involved in these antimicrobial approaches. The toxicological aspects of these advanced scaffolds are also analyzed to ensure future technological transfer to clinics. The main antimicrobial methods of characterizing scaffolds' antimicrobial and antibiofilm properties are described. The production methods of these porous supports, such as electrospinning, phase separation, gas foaming, the porogen method, polymerization in solution, fiber mesh coating, self-assembly, membrane lamination, freeze drying, 3D printing and bioprinting, among others, are also included in this article. These important advances in antimicrobial materials-based scaffolds for regenerative medicine offer many new promising avenues to the material design and tissue-engineering communities.
TL;DR: A review of surface modification methods of polyetheretherketone (PEEK) in the last five years, including surface modification of PEEK or incorporating materials into the PEEK matrix, can be found in this paper .
Abstract: Polyetheretherketone (PEEK) has gradually become the mainstream material for preparing orthopedic implants due to its similar elastic modulus to human bone, high strength, excellent wear resistance, radiolucency, and biocompatibility. Since the 1990s, PEEK has increasingly been used in orthopedics. Yet, the widespread application of PEEK is limited by its bio-inertness, hydrophobicity, and susceptibility to microbial infections. Further enhancing the osteogenic properties of PEEK-based implants remains a difficult task. This article reviews some modification methods of PEEK in the last five years, including surface modification of PEEK or incorporating materials into the PEEK matrix. For surface modification, PEEK can be modified by chemical treatment, physical treatment, or surface coating with bioactive substances. For PEEK composite material, adding bioactive filler into PEEK through the melting blending method or 3D printing technology can increase the biological activity of PEEK. In addition, some modification methods such as sulfonation treatment of PEEK or grafting antibacterial substances on PEEK can enhance the antibacterial performance of PEEK. These strategies aim to improve the bioactive and antibacterial properties of the modified PEEK. The researchers believe that these modifications could provide valuable guidance on the future design of PEEK orthopedic implants.
TL;DR: In this article , a glucose/ROS cascade-responsive nanozyme (CHA@GOx) was developed for diabetic wound treatment based on Ce-driven coassembly by a special dual ligand (alendronic acid and 2-methylimidazole) and glucose oxidase (GOx).
Abstract: Diabetic wounds have an extremely complex microenvironment of hyperglycemia, hypoxia and high reactive oxygen species (ROS). Therefore, the regulation and management of this microenvironment may provide a new and improved treatment method for chronic diabetic wound healing. Herein, a glucose/ROS cascade-responsive nanozyme (CHA@GOx) was developed for diabetic wound treatment based on Ce-driven coassembly by a special dual ligand (alendronic acid and 2-methylimidazole) and glucose oxidase (GOx). It possesses superoxide dismutase and catalase mimic activities, which effectively remove excess ROS. In particular, it can catalyze excessive hydrogen peroxide generated by the glucose oxidation reaction to produce oxygen, regulate the oxygen balance of the wound, and reduce the toxic side effects of GOx, thus achieving the purpose of synergistically repairing diabetic wounds. In vitro experiments show that CHA@GOx assists mouse fibroblast migration and promotes human umbilical vein endothelial cell tube formation. In vivo, it can induce angiogenesis, collagen deposition, and re-epithelialization during wound healing in diabetic mice. Taken together, this study indicates that the coassembly of multifunctional nanozymes has implications in diabetic wound healing.
TL;DR: In this paper , the authors introduce the sources, roles, and extraction and characterization methods of extracellular vesicles (EVs) and describe their current application status and discuss application strategies for EV-loaded hydrogels and review their specific applications in tissue regeneration and repair.
Abstract: Extracellular vesicles (EVs) are a collective term for nanoscale or microscale vesicles secreted by cells that play important biological roles. Mesenchymal stem cells are a class of cells with the potential for self-healing and multidirectional differentiation. In recent years, numerous studies have shown that EVs, especially those secreted by mesenchymal stem cells, can promote the repair and regeneration of various tissues and, thus, have significant potential in regenerative medicine. However, due to the rapid clearance capacity of the circulatory system, EVs are barely able to act persistently at specific sites for repair of target tissues. Hydrogels have good biocompatibility and loose and porous structural properties that allow them to serve as EV carriers, thereby prolonging the retention in certain specific areas and slowing the release of EVs. When EVs are needed to function at specific sites, the EV-loaded hydrogels can stand as an excellent approach. In this review, we first introduce the sources, roles, and extraction and characterization methods of EVs and describe their current application status. We then review the different types of hydrogels and discuss factors influencing their abilities to carry and release EVs. We summarize several strategies for loading EVs into hydrogels and characterizing EV-loaded hydrogels. Furthermore, we discuss application strategies for EV-loaded hydrogels and review their specific applications in tissue regeneration and repair. This article concludes with a summary of the current state of research on EV-loaded hydrogels and an outlook on future research directions, which we hope will provide promising ideas for researchers.
TL;DR: In this paper , an optimized system of epirubicin (Epi)-loaded niosomal nanoparticles (Nio) coated with hyaluronic acid (HA) has been engineered for targeting breast cancer cells.
Abstract: Targeted drug delivery systems using nanocarriers offer a versatile platform for breast cancer treatment; however, a robust, CD44-targeted niosomal formulation has not been developed and deeply studied (both in vitro and in vivo) yet. Here, an optimized system of epirubicin (Epi)-loaded niosomal nanoparticles (Nio) coated with hyaluronic acid (HA) has been engineered for targeting breast cancer cells. The nanoformulation was first optimized (based on size, polydispersity index, and entrapment efficiency); then, we characterized the morphology, stability, and release behavior of the nanoparticles. Epirubicin release from the HA-coated system (Epi-Nio-HA) showed a 21% (acidic buffer) and 20% (neutral buffer) reduction in comparison with the non-coated group (Epi-Nio). The cytotoxicity and apoptosis results of 4T1 and SkBr3 cells showed an approximately 2-fold increase in the Epi-Nio-HA system over Epi-Nio and free epirubicin, which confirms the superiority of the engineered nanocarriers. Moreover, real-time PCR data demonstrated the down-regulation of the MMP-2, MMP-9, cyclin D, and cyclin E genes expression while caspase-3 and caspase-9 gene expression were up-regulated. Confocal microscopy and flow cytometry studies uncovered the cellular uptake mechanism of the Epi-Nio-HA system, which was CD44-mediated. Furthermore, in vivo studies indicated Epi-Nio-HA decreased mice breast tumor volume by 28% (compared to epirubicin) without side effects on the liver and kidney. Conclusively, our results indicated that the HA-functionalized niosomes provide a promising nanoplatform for efficient and targeted delivery of epirubicin to potentially treat breast cancer.
TL;DR: A comprehensive overview of wear-resistant implant coatings can be found in this article , where the authors provide an overview of the most commonly used and less commonly used materials for joint replacement, both those in current clinical use and those under investigation for future use.
Abstract: Hip and knee joint replacements are common and largely successful procedures that utilise implants to restore mobility and relieve pain for patients suffering from e.g. osteoarthritis. However, metallic ions and particles released from both the bearing surfaces and non-articulating interfaces, as in modular components, can cause hypersensitivity and local tissue necrosis, while particles originating from a polymer component have been associated with aseptic loosening and osteolysis. Implant coatings have the potential to improve properties compared to both bulk metal and ceramic alternatives. Ceramic coatings have the potential to increase scratch resistance, enhance wettability and reduce wear of the articulating surfaces compared to the metallic substrate, whilst maintaining overall toughness of the implant ensuring a lower risk of catastrophic failure of the device compared to use of a bulk ceramic. Coatings can also act as barriers to inhibit ion release from the underlying material caused by corrosion. This review aims to provide a comprehensive overview of wear-resistant coatings for joint replacements - both those that are in current clinical use as well as those under investigation for future use. While the majority of coatings belong predominantly in the latter group, a few coated implants have been successfully marketed and are available for clinical use in specific applications. Commercially available coatings for implants include titanium nitride (TiN), titanium niobium nitride (TiNbN), oxidized zirconium (OxZr) and zirconium nitride (ZrN) based coatings, whereas current research is focused not only on these, but also on diamond-like-carbon (DLC), silicon nitride (SiN), chromium nitride (CrN) and tantalum-based coatings (TaN and TaO). The coating materials referred to above that are still at the research stage have been shown to be non-cytotoxic and to reduce wear in a laboratory setting. However, the adhesion of implant coatings remains a main area of concern, as poor adhesion can cause delamination and excessive wear. In clinical applications zirconium implant surfaces treated to achieve a zirconium oxide film and TiNbN coated implants have however been proven comparable to traditional cobalt chromium implants with regards to revision numbers. In addition, the chromium ion levels measured in the plasma of patients were lower and allergy symptoms were relieved. Therefore, coated implants could be considered an alternative to uncoated metal implants, in particular for patients with metal hypersensitivity. There have also been unsuccessful introductions to the market, such as DLC coated implants, and therefore this review also attempts to summarize the lessons learnt.
TL;DR: Wang et al. as mentioned in this paper developed a novel angiogenic 3D-bioprinted peptide patch to improve skin wound healing, which can fabricate individual patches according to the shape characteristics of the damaged tissue.
Abstract: Chronic wounds caused by severe trauma remain a serious challenge for clinical treatment. In this study, we developed a novel angiogenic 3D-bioprinted peptide patch to improve skin wound healing. The 3D-bioprinted technology can fabricate individual patches according to the shape characteristics of the damaged tissue. Gelatin methacryloyl (GelMA) and hyaluronic acid methacryloyl (HAMA) have excellent biocompatibility and biodegradability, and were used as a biomaterial to produce bioprinted patches. The pro-angiogenic QHREDGS peptide was covalently conjugated to the 3D-bioprinted GelMA/HAMA patches, extending the release of QHREDGS and improving the angiogenic properties of the patch. Our results demonstrated that these 3D-bioprinted peptide patches showed excellent biocompatibility, angiogenesis, and tissue repair both in vivo and in vitro. These findings indicated that 3D-bioprinted peptide patches improved skin wound healing and could be used in other tissue engineering applications.
TL;DR: In this paper , the authors developed ROS-responsive nanoparticles (NPs) as an efficacious nanomedicine against ulcerative colitis (UC) with oral administration, which exhibited an ROSresponsive size change and drug release, which benefited the ROS-scavenging and selective accumulation of LUT in the inflamed colon.
Abstract: Oxidative stress, caused by excessive production of reactive oxygen species (ROS), plays a crucial role in the occurrence and development of ulcerative colitis (UC). We developed ROS-responsive nanoparticles (NPs) as an efficacious nanomedicine against UC with oral administration. The NPs were fabricated with a d-α-tocopherol polyethylene glycol succinate-b-poly(β-thioester) copolymer (TPGS-PBTE) for ROS cleavage via the colitis-targeted delivery of luteolin (LUT), a natural flavonoid with good anti-inflammation and radical-scavenging activity. Owing to the thioether bond in the polymer main chain, the TPGS-PBTE NPs exhibited an ROS-responsive size change and drug release, which benefited the ROS-scavenging and selective accumulation of LUT in the inflamed colon. In a dextran sulfate sodium-induced acute colitis murine model, LUT@TPGS-PBTE NPs alleviated body weight loss, colon length shortening, and damage to the colonic tissues due to the suppression of ROS and proinflammatory cytokines (e.g., IL-17A, IL-6, interferon-γ, tumor necrosis factor-α), as well as upregulation of glutathione and anti-inflammatory factors (e.g., IL-10, IL-4). More importantly, LUT@TPGS-PBTE NPs regulated the inflammatory microenvironment by modulating the T helper (Th)1/Th2 and Th17/regulatory T cell (Treg) balance (i.e., increased numbers of Tregs and Th2 cells and decreased numbers of Th1 and Th17 cells), thus resolving inflammation and accelerating the healing of the intestinal mucosa. Additionally, the LUT@TPGS-PBTE NPs formulation enabled the reduction of the effective dose of LUT and showed excellent biosafety in the mouse model, demonstrating its potential as a targeted UC therapeutic oral preparation.
TL;DR: In this paper , a mussel-inspired bioactive scaffold consisting mainly of collagen and hyaluronic acid, which are natural biopolymer materials contained in human tissues, was used in clinical diabetic wound treatment as a low-cost and easily available wound dressing.
Abstract: Long-term non-healing diabetic wounds are always a serious challenge and a global healthcare burden that needs to be resolved urgently in the clinic. Prolonged inflammation and impaired angiogenesis are the main direct causes of diabetic wounds. With the development of polymer biomaterials, various wound dressings have been created, but a few of them have been applied to the clinical management of diabetic wounds. Here, we developed a mussel-inspired bioactive scaffold consisting mainly of collagen and hyaluronic acid, which are natural biopolymer materials contained in human tissues. First, we fabricated different polydopamine modified lyophilized collagen hyaluronic acid scaffolds under different concentrations of dopamine alkaline solutions, 0.5, 1, 2 mg/mL, so named CHS-PDA-0.5, CHS-PDA-1, CHS-PDA-2. After testing their physical and chemical properties, antioxidant effect, inflammation regulation, as well as drug loading and release capabilities, we obtained a bioactive endothelial growth factor (EGF)-loaded wound dressing, CHS-PDA-2@EGF, which can resist reactive oxygen species (ROS) and promote the regeneration of chronic wounds in diabetic rats by reducing inflammation. In addition, the scaffold showed excellent swelling ability, a certain coagulation effect and reasonable degradation. Therefore, the scaffold has great potential to be used in clinical diabetic wound treatment as a low-cost and easily available wound dressing to accelerate chronic wound healing.
TL;DR: In this paper , the authors systematically summarized the limits of commercial IVD biosensors of ovarian cancer and the latest discovery of new biomarkers for early ovarian cancer (OC) and proposed representative optimization strategies for six potential ovarian cancer biomarkers with emphasis on nanomaterial selection and the design of detection principles.
Abstract: The grand challenges of ovarian cancer early diagnosis have led to an alarmingly high mortality rate from ovarian cancer (OC) in the past half century. In vitro diagnosis (IVD) has great potential in the early diagnosis of OC through non-invasive and dynamic analysis of biomarkers. However, common IVDs often fail to provide reliable test results due to lack of sensitivity, specificity, and convenience. In recent years, the discovery of new biomarkers and the progress of nanomaterials can solve the shortcomings of traditional IVD for early OC. These emerging biosensors based on nanomaterials offer great improvements in convenience, speed, selectivity, and sensitivity of IVD. In this review, we firstly systematically summarized the limits of commercial IVD biosensors of OC and the latest discovery of new biomarkers for OC. The representative optimization strategies for six potential ovarian cancer biomarkers are systematically discussed with emphasis on nanomaterial selection and the design of detection principles. Then, various strategies adopted by emerging biosensors based on nanomaterials are also introduced in detail, including optical, electrochemical, microfluidic, and surface plasmon sensors. Finally, current challenges of early OC IVD are proposed, and future research directions on this promising field are also discussed.
TL;DR: In this paper , a nanofibrous mat enriched with bioactive peptides laden nano and microparticles achieved the requirements as an effective diabetic wound dressing by means of electrospinning method, fabricated Poly (lactic-co-glycolic acid)/Collagen nano-scale mat and surface functionalised with wound healing peptides, laden Chitosan nano and micro-sized particles, creating an Extracellular Matrix (ECM) -like structure with biomimetic features.
Abstract: Hard to heal wounds such as diabetic wounds is one of the major problems in the healthcare sector. Delayed healing and shortfall of functional restoration at the wound site require upgraded wound management aids. In this study, we report that a nanofibrous mat enriched with bioactive peptides laden nano and microparticles achieve the requirements as an effective diabetic wound dressing. By means of electrospinning method, we fabricated Poly (lactic-co-glycolic acid)/Collagen nano-scale mat and surface functionalised with wound healing peptides, laden Chitosan nano and micro-sized particles, creating an Extracellular Matrix (ECM) -like structure with biomimetic features. The developed dressing displayed good cytocompatibility with Keratinocyte and fibroblast cells and enhanced their in-vitro cell proliferation and migration. Experiments in the streptozotocin-induced diabetic mice model showed that bioactive peptides released from Chitosan particles shorten the inflammatory stage and promote neovascularisation. The supporting nanoscale matrix promotes increased collagen deposition in the wound beds, thereby hastening the complete healing process by substantial tissue re-generation and functional restoration. The results evince that the nano/microparticles enriched nano-scale mat show potential as an effective wound repair dressing for diabetic wounds.
TL;DR: Wang et al. as mentioned in this paper describe varied building blocks of silk at different levels used in biomedical field and their effective extraction and reconstruction strategies, and present recent discoveries and research progresses on how these functional regenerated silk fibroin (RSF) biomaterials used in advanced biomedical applications, especially in the fields of cell-material interactions, soft tissue regeneration, and flexible bioelectronic devices.
Abstract: Silk fibroin has become a promising biomaterial owing to its remarkable mechanical property, biocompatibility, biodegradability, and sufficient supply. However, it is difficult to directly construct materials with other formats except for yarn, fabric and nonwoven based on natural silk. A promising bioinspired strategy is firstly extracting desired building blocks of silk, then reconstructing them into functional regenerated silk fibroin (RSF) materials with controllable formats and structures. This strategy could give it excellent processability and modifiability, thus well meet the diversified needs in biomedical applications. Recently, to engineer RSF materials with properties similar to or beyond the hierarchical structured natural silk, novel extraction and reconstruction strategies have been developed. In this review, we seek to describe varied building blocks of silk at different levels used in biomedical field and their effective extraction and reconstruction strategies. This review also present recent discoveries and research progresses on how these functional RSF biomaterials used in advanced biomedical applications, especially in the fields of cell-material interactions, soft tissue regeneration, and flexible bioelectronic devices. Finally, potential study and application for future opportunities, and current challenges for these bioinspired strategies and corresponding usage were also comprehensively discussed. In this way, it aims to provide valuable references for the design and modification of novel silk biomaterials, and further promote the high-quality-utilization of silk or other biopolymers.
TL;DR: In this article , platelet-rich plasma (PRP)-integrated alginate-gelatin (AG) composite hydrogel bioinks were evaluated in vitro and in vivo.
Abstract: In-situ three-dimensional (3D) bioprinting has been emerging as a promising technology designed to rapidly seal cutaneous defects according to their contour. Improvements in the formulations of multi-component bioink are needed to support cytocompatible encapsulation and biological functions. Platelet-rich plasma (PRP), as a source of patient-specific autologous growth factors, exhibits capabilities in tissue repair and rejuvenation. This study aimed to prepare PRP-integrated alginate-gelatin (AG) composite hydrogel bioinks and evaluate the biological effects in vitro and in vivo. 3D bioprinted constructs embedded with dermal fibroblasts and epidermal stem cells were fabricated using extrusion strategy. The integration of PRP not only improved the cellular behavior of seeded cells, but regulate the tube formation of vascular endothelial cells and macrophage polarization in a paracrine manner, which obtained an optimal effect at an incorporation concentration of 5%. For in-situ bioprinting, PRP integration accelerated the high-quality wound closure, modulated the inflammation and initiated the angiogenesis compared with the AG bioink. In conclusion, we revealed the regenerative potential of PRP, readily available at the bedside, as an initial signaling provider in multi-component bioink development. Combined with in-situ printing technology, it is expected to accelerate the clinical translation of rapid individualized wound repair.
TL;DR: In this paper , the authors provide an overview of naturally occurring slimy substances with adhesive properties and categorize them in terms of the main chemical motifs that convey their stickiness, i.e., carbohydrate-, protein-, and glycoprotein-based biological glues.
Abstract: With the "many-headed" slime mold Physarum polycelphalum having been voted the unicellular organism of the year 2021 by the German Society of Protozoology, we are reminded that a large part of nature's huge variety of life forms is easily overlooked - both by the general public and researchers alike. Indeed, whereas several animals such as mussels or spiders have already inspired many scientists to create novel materials with glue-like properties, there is much more to discover in the flora and fauna. Here, we provide an overview of naturally occurring slimy substances with adhesive properties and categorize them in terms of the main chemical motifs that convey their stickiness, i.e., carbohydrate-, protein-, and glycoprotein-based biological glues. Furthermore, we highlight selected recent developments in the area of material design and functionalization that aim at making use of such biological compounds for novel applications in medicine - either by conjugating adhesive motifs found in nature to biological or synthetic macromolecules or by synthetically creating (multi-)functional materials, which combine adhesive properties with additional, problem-specific (and sometimes tunable) features.
TL;DR: In this paper , dissolving and implantable microneedle array patches (MAPs) loaded with the tenofovir alafenamide (TAF) were developed with the aim of releasing the drug systemically.
Abstract: The human immunodeficiency virus (HIV) remains a global health concern, with 37.7 million people currently living with the infection and 1.5 million new cases every year. Current antiretroviral (ARV) therapies are administered through the oral route daily, often in lifelong treatments, leading to pill fatigue and poor treatment adherence. Therefore, the development of novel formulations for the administration ARV drugs using alternative routes is actively sought out. In this sense, microneedle array patches (MAPs) offer a unique user-centric platform that can be painlessly self-applied to the skin and deliver drugs to the systemic circulation. In this work, dissolving and implantable MAPs loaded with the tenofovir alafenamide (TAF) were developed with the aim of releasing the drug systemically. Both MAPs were sufficiently strong to pierce excised neonatal full-thickness porcine skin and form drug depots. In vitro release experiments performed in dialysis membrane models, demonstrated a relatively fast delivery of the drug in all cases. Franz cells experiments revealed that dissolving and implantable MAPs deposited 47.87 ± 16.33 μg and 1208.04 ± 417.9 μg of TAF in the skin after 24 h. Pharmacokinetic experiments in rats demonstrated a fast metabolization of TAF into tenofovir, with a rapid elimination of the metabolite from the plasma. The MAPs described in this work could be used as an alternative to current oral treatments for HIV management.
TL;DR: GelMAC as discussed by the authors is a double-crosslinked sealant which showed excellent hemostasis (comparable to existing commercial hemostat) without compromising its wet tissue adhesion and controlled the bleeding through its wound-sealing capability and inherent chemical activity.
Abstract: Controlling bleeding from a raptured tissue, especially during the surgeries, is essentially important. Particularly for soft and dynamic internal organs where use of sutures, staples, or wires is limited, treatments with hemostatic adhesives have proven to be beneficial. However, major drawbacks with clinically used hemostats include lack of adhesion to wet tissue and poor mechanics. In view of these, herein, we engineered a double-crosslinked sealant which showed excellent hemostasis (comparable to existing commercial hemostat) without compromising its wet tissue adhesion. Mechanistically, the engineered hydrogel controlled the bleeding through its wound-sealing capability and inherent chemical activity. This mussel-inspired hemostatic adhesive hydrogel, named gelatin methacryloyl-catechol (GelMAC), contained covalently functionalized catechol and methacrylate moieties and showed excellent biocompatibility both in vitro and in vivo. Hemostatic property of GelMAC hydrogel was initially demonstrated with an in vitro blood clotting assay, which showed significantly reduced clotting time compared to the clinically used hemostat, Surgicel®. This was further assessed with an in vivo liver bleeding test in rats where GelMAC hydrogel closed the incision rapidly and initiated blood coagulation even faster than Surgicel®. The engineered GelMAC hydrogel-based seaalant with excellent hemostatic property and tissue adhesion can be utilized for controlling bleeding and sealing of soft internal organs.
TL;DR: In this article , vascular endothelial cells laden with thermosensitive bio-ink were bioprinted in situ on the inner surfaces of interconnected tubular channels of bone mesenchymal stem cell-laden 3D-biopsrinted scaffolds.
Abstract: Large bone defects remain an unsolved clinical challenge because of the lack of effective vascularization in newly formed bone tissue. 3D bioprinting is a fabrication technology with the potential to create vascularized bone grafts with biological activity for repairing bone defects. In this study, vascular endothelial cells laden with thermosensitive bio-ink were bioprinted in situ on the inner surfaces of interconnected tubular channels of bone mesenchymal stem cell-laden 3D-bioprinted scaffolds. Endothelial cells exhibited a more uniform distribution and greater seeding efficiency throughout the channels. In vitro, the in situ bioprinted endothelial cells can form a vascular network through proliferation and migration. The in situ vascularized tissue-engineered bone also resulted in a coupling effect between angiogenesis and osteogenesis. Moreover, RNA sequencing analysis revealed that the expression of genes related to osteogenesis and angiogenesis is upregulated in biological processes. The in vivo 3D-bioprinted in situ vascularized scaffolds exhibited excellent performance in promoting new bone formation in rat calvarial critical-sized defect models. Consequently, in situ vascularized tissue-engineered bones constructed using 3D bioprinting technology have a potential of being used as bone grafts for repairing large bone defects, with a possible clinical application in the future.
TL;DR: Based on the exosome secreted by adipose-derived stem cells (ADSC-exo), Zhang et al. as discussed by the authors loaded ADSCexo into the matrix metalloproteinase degradable polyethylene glycol (MMP-PEG) smart hydrogel.
Abstract: Diabetic wound complications are financially costly and difficult to heal in worldwide. Whereas the therapies of diabetic wound, such as wound dressing, endocrine therapy or flap-transplantations, were not satisfied. Based on our previous study of exosome secreted by adipose-derived stem cell (ADSC-exo), we loaded ADSC-exo into the matrix metalloproteinase degradable polyethylene glycol (MMP-PEG) smart hydrogel. Physical and chemical properties of ADSC-exo@MMP-PEG smart hydrogel were tested by scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FTIR), weight loss examination, etc. As the hydrogel degraded in response to MMP, ADSC-exo was released and subsequently enhanced cell function via Akt signaling. Moreover, treatment with ADSC-exo@MMP-PEG smart hydrogel significantly relieved the H2O2-induced oxidative stress, which was widely recognized as a major cause of diabetic wound nonhealing. Similar results were achieved in mice diabetic wound models, in which the ADSC-exo@MMP-PEG treatment group displayed a significantly accelerated wound healing. To summarize, the present smart hydrogel with enzyme-response and exosome-release was proved to be benefit for diabetic wounds healing, which provides a reliable theoretical basis for application of ADSC-exo in treatment of diabetic wounds.