Alveolar bone loss is widespread in all age groups and remains a severe hazard to periodontal health. Horizontal alveolar bone loss is the pattern of bone loss more commonly seen in periodontitis. Until now, limited regenerative procedures have been applied to treating horizontal alveolar bone loss in periodontal clinics, making it the least predictable periodontal defect type. This article reviews the literature on recent advances in horizontal alveolar bone regeneration. The biomaterials and clinical and preclinical approaches tested for the regeneration of the horizontal type of alveolar bone are first discussed. Furthermore, current obstacles for horizontal alveolar bone regeneration and future directions in regenerative therapy are presented to provide new ideas for developing an effective multidisciplinary strategy to address the challenge of horizontal alveolar bone loss.
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Biomedical Materials publishes original research findings and critical reviews that contribute to our knowledge about the composition, properties, and performance of materials for all applications relevant to human healthcare.
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Tiancheng Li et al 2023 Biomed. Mater. 18 052004
Farah N S Raja et al 2023 Biomed. Mater. 18 045003
With the advent of nanotechnology, there has been an extensive interest in the antimicrobial potential of metals. The rapid and widespread development of antimicrobial-resistant and multidrug-resistant bacteria has prompted recent research into developing novel or alternative antimicrobial agents. In this study, the antimicrobial efficacy of metallic copper, cobalt, silver and zinc nanoparticles was assessed against Escherichia coli (NCTC 10538), S. aureus (ATCC 6538) along with three clinical isolates of Staphylococcus epidermidis (A37, A57 and A91) and three clinical isolates of E. coli (Strains 1, 2 and 3) recovered from bone marrow transplant patients and patients with cystitis respectively. Antimicrobial sensitivity assays, including agar diffusion and broth macro-dilution to determine minimum inhibitory and bactericidal concentrations (MIC/MBC) and time-kill/synergy assays, were used to assess the antimicrobial efficacy of the agents. The panel of test microorganisms, including antibiotic-resistant strains, demonstrated a broad range of sensitivity to the metals investigated. MICs of the type culture strains were in the range of 0.625–5.0 mg ml−1. While copper and cobalt exhibited no difference in sensitivity between Gram-positive and Gram-negative microorganisms, silver and zinc showed strain specificity. A significant decrease (p < 0.001) in the bacterial density of E. coli and S. aureus was demonstrated by silver, copper and zinc in as little as two hours. Furthermore, combining metal nanoparticles reduced the time required to achieve a complete kill.
Rosemond A Mensah et al 2023 Biomed. Mater. 18 042001
Naturally derived materials are often preferred over synthetic materials for biomedical applications due to their innate biological characteristics, relative availability, sustainability, and agreement with conscientious end-users. The chicken eggshell membrane (ESM) is an abundant resource with a defined structural profile, chemical composition, and validated morphological and mechanical characteristics. These unique properties have not only allowed the ESM to be exploited within the food industry but has also led to it be considered for other novel translational applications such as tissue regeneration and replacement, wound healing and drug delivery. However, challenges still exist in order to enhance the native ESM (nESM): the need to improve its mechanical properties, the ability to combine/join fragments of ESM together, and the addition or incorporation of drugs/growth factors to advance its therapeutic capacity. This review article provides a succinct background to the nESM, its extraction, isolation, and consequent physical, mechanical and biological characterisation including possible approaches to enhancement. Moreover, it also highlights current applications of the ESM in regenerative medicine and hints at future novel applications in which this novel biomaterial could be exploited to beneficial use.
Wenjing Yin et al 2024 Biomed. Mater. 19 032002
Exosomes, typically 30–150 nm in size, are lipid-bilayered small-membrane vesicles originating in endosomes. Exosome biogenesis is regulated by the coordination of various mechanisms whereby different cargoes (e.g. proteins, nucleic acids, and lipids) are sorted into exosomes. These components endow exosomes with bioregulatory functions related to signal transmission and intercellular communication. Exosomes exhibit substantial potential as drug-delivery nanoplatforms owing to their excellent biocompatibility and low immunogenicity. Proteins, miRNA, siRNA, mRNA, and drugs have been successfully loaded into exosomes, and these exosome-based delivery systems show satisfactory therapeutic effects in different disease models. To enable targeted drug delivery, genetic engineering and chemical modification of the lipid bilayer of exosomes are performed. Stimuli-responsive delivery nanoplatforms designed with appropriate modifications based on various stimuli allow precise control of on-demand drug delivery and can be utilized in clinical treatment. In this review, we summarize the general properties, isolation methods, characterization, biological functions, and the potential role of exosomes in therapeutic delivery systems. Moreover, the effective combination of the intrinsic advantages of exosomes and advanced bioengineering, materials science, and clinical translational technologies are required to accelerate the development of exosome-based delivery nanoplatforms.
E B Ibitoye et al 2018 Biomed. Mater. 13 025009
Chitin ranks next to cellulose as the most important bio-polysaccharide which can primarily be extracted from crustacean shells. However, the emergence of new areas of the application of chitin and its derivatives are on the increase and there is growing demand for new chitin sources. In this study, therefore, an attempt was made to extract chitin from the house cricket (Brachytrupes portentosus) by a chemical method. The physicochemical properties of chitin and chitosan extracted from crickets were compared with commercial chitin and chitosan extracted from shrimps, in terms of proximate analysis in particular, of their ash and moisture content. Also, infrared spectroscopy, x-ray diffraction (XRD), scanning electron microscopy and elemental analysis were conducted. The chitin and chitosan yield of the house cricket ranges over 4.3%–7.1% and 2.4%–5.8% respectively. Chitin and chitosan from crickets compares favourably with those extracted from shrimps, and were found to exhibit some similarities. The result shows that cricket and shrimp chitin and chitosan have the same degree of acetylation and degree of deacetylation of 108.1% and 80.5% respectively, following Fourier transform infrared spectroscopy. The characteristic XRD strong/sharp peaks of 9.4 and 19.4° for α-chitin are common for both cricket and shrimp chitin. The percentage ash content of chitin and chitosan extracted from B. portentosus is 1%, which is lower than that obtained from shrimp products. Therefore, cricket chitin and chitosan can be said to be of better quality and of purer form than commercially produced chitin and chitosan from shrimp. Based on the quality of the product, chitin and chitosan isolated from B. portentosus can replace commercial chitin and chitosan in terms of utilization and applications. Therefore, B. portentosus is a promising alternative source of chitin and chitosan.
Gurpreet Singh and Arnab Chanda 2021 Biomed. Mater. 16 062004
The mechanical properties of soft tissues play a key role in studying human injuries and their mitigation strategies. While such properties are indispensable for computational modelling of biological systems, they serve as important references in loading and failure experiments, and also for the development of tissue simulants. To date, experimental studies have measured the mechanical properties of peripheral tissues (e.g. skin) in-vivo and limited internal tissues ex-vivo in cadavers (e.g. brain and the heart). The lack of knowledge on a majority of human tissues inhibit their study for applications ranging from surgical planning, ballistic testing, implantable medical device development, and the assessment of traumatic injuries. The purpose of this work is to overcome such challenges through an extensive review of the literature reporting the mechanical properties of whole-body soft tissues from head to toe. Specifically, the available linear mechanical properties of all human tissues were compiled. Non-linear biomechanical models were also introduced, and the soft human tissues characterized using such models were summarized. The literature gaps identified from this work will help future biomechanical studies on soft human tissue characterization and the development of accurate medical models for the study and mitigation of injuries.
Haiyu Yu et al 2024 Biomed. Mater. 19 042002
Porous tantalum scaffolds offer a high degree of biocompatibility and have a low friction coefficient. In addition, their biomimetic porous structure and mechanical properties, which closely resemble human bone tissue, make them a popular area of research in the field of bone defect repair. With the rapid advancement of additive manufacturing, 3D-printed porous tantalum scaffolds have increasingly emerged in recent years, offering exceptional design flexibility, as well as facilitating the fabrication of intricate geometries and complex pore structures that similar to human anatomy. This review provides a comprehensive description of the techniques, procedures, and specific parameters involved in the 3D printing of porous tantalum scaffolds. Concurrently, the review provides a summary of the mechanical properties, osteogenesis and antibacterial properties of porous tantalum scaffolds. The use of surface modification techniques and the drug carriers can enhance the characteristics of porous tantalum scaffolds. Accordingly, the review discusses the application of these porous tantalum materials in clinical settings. Multiple studies have demonstrated that 3D-printed porous tantalum scaffolds exhibit exceptional corrosion resistance, biocompatibility, and osteogenic properties. As a result, they are considered highly suitable biomaterials for repairing bone defects. Despite the rapid development of 3D-printed porous tantalum scaffolds, they still encounter challenges and issues when used as bone defect implants in clinical applications. Ultimately, a concise overview of the primary challenges faced by 3D-printed porous tantalum scaffolds is offered, and corresponding insights to promote further exploration and advancement in this domain are presented.
Zhi Chen et al 2018 Biomed. Mater. 13 032002
Corneal transplantation is an important surgical treatment for many common corneal diseases. However, a worldwide shortage of tissue from suitable corneal donors has meant that many people are not able to receive sight-restoring operations. In addition, rejection is a major cause of corneal transplant failure. Bioengineering corneal tissue has recently gained widespread attention. In order to facilitate corneal regeneration, a range of materials is currently being investigated. The ideal substrate requires sufficient tectonic durability, biocompatibility with cultured cellular elements, transparency, and perhaps biodegradability and clinical compliance. This review considers the anatomy and function of the native cornea as a precursor to evaluating a variety of biomaterials for corneal regeneration including key characteristics for optimal material form and function. The integration of appropriate cells with the most appropriate biomaterials is also discussed. Taken together, the information provided offers insight into the requirements for fabricating synthetic and semisynthetic corneas for in vitro modeling of tissue development and disease, pharmaceutical screening, and in vivo application for regenerative medicine.
Memoona Akhtar et al 2024 Biomed. Mater. 19 035016
The present work focuses on developing 5% w/v oxidized alginate (alginate di aldehyde, ADA)-7.5% w/v gelatin (GEL) hydrogels incorporating 0.25% w/v silk fibroin (SF) and loaded with 0.3% w/v Cu-Ag doped mesoporous bioactive glass nanoparticles (Cu-Ag MBGNs). The microstructural, mechanical, and biological properties of the composite hydrogels were characterized in detail. The porous microstructure of the developed ADA-GEL based hydrogels was confirmed by scanning electron microscopy, while the presence of Cu-Ag MBGNs in the synthesized hydrogels was determined using energy dispersive x-ray spectroscopy. The incorporation of 0.3% w/v Cu-Ag MBGNs reduced the mechanical properties of the synthesized hydrogels, as investigated using micro-tensile testing. The synthesized ADA-GEL loaded with 0.25% w/v SF and 0.3% w/v Cu-Ag MBGNs showed a potent antibacterial effect against Escherichia coli and Staphylococcus aureus. Cellular studies using the NIH3T3-E1 fibroblast cell line confirmed that ADA-GEL films incorporated with 0.3% w/v Cu-Ag MBGNs exhibited promising cellular viability as compared to pure ADA-GEL (determined by WST-8 assay). The addition of SF improved the biocompatibility, degradation rate, moisturizing effects, and stretchability of the developed hydrogels, as determined in vitro. Such multimaterial hydrogels can stimulate angiogenesis and exhibit desirable antibacterial properties. Therefore further (in vivo) tests are justified to assess the hydrogels' potential for wound dressing and skin tissue healing applications.
Xiaoming Liu et al 2024 Biomed. Mater. 19 042004
In the field of medicine, we often brave the unknown like interstellar explorers, especially when confronting the formidable opponent of hepatocellular carcinoma (HCC). The global burden of HCC remains significant, with suboptimal treatment outcomes necessitating the urgent development of novel drugs and treatments. While various treatments for liver cancer, such as immunotherapy and targeted therapy, have emerged in recent years, improving their transport and therapeutic efficiency, controlling their targeting and release, and mitigating their adverse effects remains challenging. However, just as we grope through the darkness, a glimmer of light emerges—nanotechnology. Recently, nanotechnology has attracted attention because it can increase the local drug concentration in tumors, reduce systemic toxicity, and has the potential to enhance the effectiveness of precision therapy for HCC. However, there are also some challenges hindering the clinical translation of drug-loaded nanoparticles (NPs). Just as interstellar explorers must overcome interstellar dust, we too must overcome various obstacles. In future researches, the design and development of nanodelivery systems for novel drugs treating HCC should be the first attention. Moreover, researchers should focus on the active targeting design of various NPs. The combination of the interventional therapies and drug-loaded NPs will greatly advance the process of precision HCC therapy.
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Sheersha Pramanik et al 2024 Biomed. Mater. 19 042008
Gelatin methacryloyl (GelMA) hydrogels have gained significant recognition as versatile biomaterials in the biomedical domain. GelMA hydrogels emulate vital characteristics of the innate extracellular matrix by integrating cell-adhering and matrix metalloproteinase-responsive peptide motifs. These features enable cellular proliferation and spreading within GelMA-based hydrogel scaffolds. Moreover, GelMA displays flexibility in processing, as it experiences crosslinking when exposed to light irradiation, supporting the development of hydrogels with adjustable mechanical characteristics. The drug delivery landscape has been reshaped by GelMA hydrogels, offering a favorable platform for the controlled and sustained release of therapeutic actives. The tunable physicochemical characteristics of GelMA enable precise modulation of the kinetics of drug release, ensuring optimal therapeutic effectiveness. In tissue engineering, GelMA hydrogels perform an essential role in the design of the scaffold, providing a biomimetic environment conducive to cell adhesion, proliferation, and differentiation. Incorporating GelMA in three-dimensional printing further improves its applicability in drug delivery and developing complicated tissue constructs with spatial precision. Wound healing applications showcase GelMA hydrogels as bioactive dressings, fostering a conducive microenvironment for tissue regeneration. The inherent biocompatibility and tunable mechanical characteristics of GelMA provide its efficiency in the closure of wounds and tissue repair. GelMA hydrogels stand at the forefront of biomedical innovation, offering a versatile platform for addressing diverse challenges in drug delivery, tissue engineering, and wound healing. This review provides a comprehensive overview, fostering an in-depth understanding of GelMA hydrogel's potential impact on progressing biomedical sciences.
Yingnan Sun et al 2024 Biomed. Mater. 19 045018
Single-cell analysis is an effective method for conducting comprehensive heterogeneity studies ranging from cell phenotype to gene expression. The ability to arrange different cells in a predetermined pattern at single-cell resolution has a wide range of applications in cell-based analysis and plays an important role in facilitating interdisciplinary research by researchers in various fields. Most existing microfluidic microwell chips is a simple and straightforward method, which typically use small-sized microwells to accommodate single cells. However, this method imposes certain limitations on cells of various sizes, and the single-cell capture efficiency is relatively low without the assistance of external forces. Moreover, the microwells limit the spatiotemporal resolution of reagent replacement, as well as cell-to-cell communication. In this study, we propose a new strategy to prepare a single-cell array on a planar microchannel based on microfluidic flip microwells chip platform with large apertures (50 μm), shallow channels (50 μm), and deep microwells (50 μm). The combination of three configuration characteristics contributes to multi-cell trapping and a single-cell array within microwells, while the subsequent chip flipping accomplishes the transfer of the single-cell array to the opposite planar microchannel for cells adherence and growth. Further assisted by protein coating of bovine serum albumin and fibronectin on different layers, the single-cell capture efficiency in microwells is achieved at 92.1% ± 1%, while ultimately 85% ± 3.4% on planar microchannel. To verify the microfluidic flip microwells chip platform, the real-time and heterogeneous study of calcium release and apoptosis behaviours of single cells is carried out. To our knowledge, this is the first time that high-efficiency single-cell acquisition has been accomplished using a circular-well chip design that combines shallow channel, large aperture and deep microwell together. The chip is effective in avoiding the shearing force of high flow rates on cells, and the large apertures better allows cells to sedimentation. Therefore, this strategy owns the advantages of easy preparation and user-friendliness, which is especially valuable for researchers from different fields.
Marziyeh Ranjbar-Mohammadi et al 2024 Biomed. Mater. 19 045017
With the increasing prevalence of diabetes, the healing of diabetic wounds has become a significant challenge for both healthcare professionals and patients. Recognizing the urgent need for effective solutions, it is crucial to develop suitable scaffolds specifically tailored for diabetic wound healing. In line with this objective, we have developed novel hybrid nanofibrous scaffolds by combining polyvinyl alcohol/chitosan (PVA/CS) and gelatin/poly(ε-caprolactone) (Gel/PCL) polymers through a double-nozzle electrospinning technique. In this study, we investigated the influence of the Gel/PCL blend ratio on the properties of the resulting nanofibers. Three different hybrid scaffold structures were examined: Gel/PCL (80:20)-PVA/CS (80:20), Gel/PCL (50:50)-PVA/CS (80:20), and Gel/PVA (20:80)-PVA/CS (80:20). Our findings demonstrate that the electrospun nanofibers of PVA/CS (80:20)-Gel/PCL (80:20) exhibited optimal mechanical performance, with a contact angle of approximately 54° and a diameter of 183 nm. Considering the crucial role of inhibiting bacterial adhesion in the success of implanted materials, we evaluated the cytocompatibility of the hybrid electrospun nanofibers using mouse fibroblast cells (L-929 cells). The in vitro cytotoxicity results obtained from L-929 fibroblast cell culture on the hybrid scaffolds revealed enhanced cell proliferation and appropriate cell morphology on the PVA/CS (80:20)-Gel/PCL (80:20) sample, indicating its capability to support tissue cell integration. Based on the information obtained from this study, the fabricated hybrid scaffold holds great promise for diabetic ulcer healing. Its optimal mechanical properties, suitable contact angle, and favorable cytocompatibility highlight its potential as a valuable tool in the field of diabetic wound healing. The development of such hybrid scaffolds represents a significant step forward in addressing the challenges associated with diabetic wound care.
Yuanyuan Li et al 2024 Biomed. Mater. 19 045016
Bacterial biofilm formation is associated with the pathogenicity of pathogens and poses a serious threat to human health and clinical therapy. Complex biofilm structures provide physical barriers that inhibit antibiotic penetration and inactivate antibiotics via enzymatic breakdown. The development of biofilm-disrupting nanoparticles offers a promising strategy for combating biofilm infections. Hence, polyethyleneimine surface-modified silver-selenium nanocomposites, Ag@Se@PEI (ASP NCs), were designed for synergistic antibacterial effects by destroying bacterial biofilms to promote wound healing. The results of in vitro antimicrobial experiments showed that, ASP NCs achieved efficient antibacterial effects against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) by disrupting the formation of the bacterial biofilm, stimulating the outbreak of reactive oxygen species and destroying the integrity of bacterial cell membranes. The in-vivo bacterial infection in mice model showed that, ASP NCs further promoted wound healing and new tissue formation by reducing inflammatory factors and promoting collagen fiber formation which efficiently enhanced the antibacterial effect. Overall, ASP NCs possess low toxicity and minimal side effects, coupled with biocompatibility and efficient antibacterial properties. By disrupting biofilms and bacterial cell membranes, ASP NCs reduced inflammatory responses and accelerated the healing of infected wounds. This nanocomposite-based study offers new insights into antibacterial therapeutic strategies as potential alternatives to antibiotics for wound healing.
Cuiling Ouyang et al 2024 Biomed. Mater. 19 045015
The traditional chemotherapeutic agents' disadvantages such as high toxicity, untargeting and poor water solubility lead to disappointing chemotherapy effects, which restricts its clinical application. In this work, novel size-appropriate and glutathione (GSH)-responsive nano-hydrogels were successfully prepared via the active ester method between chitosan (containing –NH2) and cross-linker (containing NHS). Especially, the cross-linker was elaborately designed to possess a disulfide linkage (SS) as well as two terminal NHS groups, namely NHS–SS–NHS. These functionalities endowed chitosan-based cross-linked scaffolds with capabilities for drug loading and delivery, as well as a GSH-responsive mechanism for drug release. The prepared nano-hydrogels demonstrated excellent performance applicable morphology, excellent drug loading efficiency (∼22.5%), suitable size (∼100 nm) and long-term stability. The prepared nano-hydrogels released over 80% doxorubicin (DOX) after incubation in 10 mM GSH while a minimal DOX release less than 25% was tested in normal physiological buffer (pH = 7.4). The unloaded nano-hydrogels did not show any apparent cytotoxicity to A 549 cells. In contrast, DOX-loaded nano-hydrogels exhibited marked anti-tumor activity against A 549 cells, especially in high GSH environment. Finally, through fluorescent imaging and flow cytometry analysis, fluorescein isothiocyanate-labeled nano-hydrogels show obvious specific binding to the GSH high-expressing A549 cells and nonspecific binding to the GSH low-expressing A549 cells. Therefore, with this cross-linking approach, our present finding suggests that cross-linked chitosan nano-hydrogel drug carrier improves the anti-tumor effect of the A 549 cells and may serve as a potential injectable delivery carrier.
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Sheersha Pramanik et al 2024 Biomed. Mater. 19 042008
Gelatin methacryloyl (GelMA) hydrogels have gained significant recognition as versatile biomaterials in the biomedical domain. GelMA hydrogels emulate vital characteristics of the innate extracellular matrix by integrating cell-adhering and matrix metalloproteinase-responsive peptide motifs. These features enable cellular proliferation and spreading within GelMA-based hydrogel scaffolds. Moreover, GelMA displays flexibility in processing, as it experiences crosslinking when exposed to light irradiation, supporting the development of hydrogels with adjustable mechanical characteristics. The drug delivery landscape has been reshaped by GelMA hydrogels, offering a favorable platform for the controlled and sustained release of therapeutic actives. The tunable physicochemical characteristics of GelMA enable precise modulation of the kinetics of drug release, ensuring optimal therapeutic effectiveness. In tissue engineering, GelMA hydrogels perform an essential role in the design of the scaffold, providing a biomimetic environment conducive to cell adhesion, proliferation, and differentiation. Incorporating GelMA in three-dimensional printing further improves its applicability in drug delivery and developing complicated tissue constructs with spatial precision. Wound healing applications showcase GelMA hydrogels as bioactive dressings, fostering a conducive microenvironment for tissue regeneration. The inherent biocompatibility and tunable mechanical characteristics of GelMA provide its efficiency in the closure of wounds and tissue repair. GelMA hydrogels stand at the forefront of biomedical innovation, offering a versatile platform for addressing diverse challenges in drug delivery, tissue engineering, and wound healing. This review provides a comprehensive overview, fostering an in-depth understanding of GelMA hydrogel's potential impact on progressing biomedical sciences.
Armaghan Moghaddam et al 2024 Biomed. Mater. 19 042007
Bone tissue engineering (BTE) provides the treatment possibility for segmental long bone defects that are currently an orthopedic dilemma. This review explains different strategies, from biological, material, and preparation points of view, such as using different stem cells, ceramics, and metals, and their corresponding properties for BTE applications. In addition, factors such as porosity, surface chemistry, hydrophilicity and degradation behavior that affect scaffold success are introduced. Besides, the most widely used production methods that result in porous materials are discussed. Gene delivery and secretome-based therapies are also introduced as a new generation of therapies. This review outlines the positive results and important limitations remaining in the clinical application of novel BTE materials and methods for segmental defects.
Yinan Jia et al 2024 Biomed. Mater. 19 042006
Infectious diseases caused by bacterial infections are common in clinical practice. Cell membrane coating nanotechnology represents a pioneering approach for the delivery of therapeutic agents without being cleared by the immune system in the meantime. And the mechanism of infection treatment should be divided into two parts: suppression of pathogenic bacteria and suppression of excessive immune response. The membrane-coated nanoparticles exert anti-bacterial function by neutralizing exotoxins and endotoxins, and some other bacterial proteins. Inflammation, the second procedure of bacterial infection, can also be suppressed through targeting the inflamed site, neutralization of toxins, and the suppression of pro-inflammatory cytokines. And platelet membrane can affect the complement process to suppress inflammation. Membrane-coated nanoparticles treat bacterial infections through the combined action of membranes and nanoparticles, and diagnose by imaging, forming a theranostic system. Several strategies have been discovered to enhance the anti-bacterial/anti-inflammatory capability, such as synthesizing the material through electroporation, pretreating with the corresponding pathogen, membrane hybridization, or incorporating with genetic modification, lipid insertion, and click chemistry. Here we aim to provide a comprehensive overview of the current knowledge regarding the application of membrane-coated nanoparticles in preventing bacterial infections as well as addressing existing uncertainties and misconceptions.
Xiaoming Liu et al 2024 Biomed. Mater. 19 042004
In the field of medicine, we often brave the unknown like interstellar explorers, especially when confronting the formidable opponent of hepatocellular carcinoma (HCC). The global burden of HCC remains significant, with suboptimal treatment outcomes necessitating the urgent development of novel drugs and treatments. While various treatments for liver cancer, such as immunotherapy and targeted therapy, have emerged in recent years, improving their transport and therapeutic efficiency, controlling their targeting and release, and mitigating their adverse effects remains challenging. However, just as we grope through the darkness, a glimmer of light emerges—nanotechnology. Recently, nanotechnology has attracted attention because it can increase the local drug concentration in tumors, reduce systemic toxicity, and has the potential to enhance the effectiveness of precision therapy for HCC. However, there are also some challenges hindering the clinical translation of drug-loaded nanoparticles (NPs). Just as interstellar explorers must overcome interstellar dust, we too must overcome various obstacles. In future researches, the design and development of nanodelivery systems for novel drugs treating HCC should be the first attention. Moreover, researchers should focus on the active targeting design of various NPs. The combination of the interventional therapies and drug-loaded NPs will greatly advance the process of precision HCC therapy.
Chenguang Wang et al 2024 Biomed. Mater. 19 042003
Infectious diseases severely threaten human health, and traditional treatment techniques face multiple limitations. As an important component of immune cells, macrophages display unique biological properties, such as biocompatibility, immunocompatibility, targeting specificity, and immunoregulatory activity, and play a critical role in protecting the body against infections. The macrophage membrane-coated nanoparticles not only maintain the functions of the inner nanoparticles but also inherit the characteristics of macrophages, making them excellent tools for improving drug delivery and therapeutic implications in infectious diseases (IDs). In this review, we describe the characteristics and functions of macrophage membrane-coated nanoparticles and their advantages and challenges in ID therapy. We first summarize the pathological features of IDs, providing insight into how to fight them. Next, we focus on the classification, characteristics, and preparation of macrophage membrane-coated nanoparticles. Finally, we comprehensively describe the progress of macrophage membrane-coated nanoparticles in combating IDs, including drug delivery, inhibition and killing of pathogens, and immune modulation. At the end of this review, a look forward to the challenges of this aspect is presented.
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Du et al
The development of a composite sponge with high water absorbency and active coagulation mechanism for traumatic hemostasis and anti-infection remains a challenge. Herein, we developed a composite sponge using gelation, swelling, and freeze-drying methods based on quaternized chitosan, succinimidyl-modified F127, and bioactive glass. The sponge exhibited macroporous structure, high porosity, and water absorbency. When exposed to blood, it strongly interacted with blood cells, promoting their adhesion, aggregation, and activation. Moreover, it activated the intrinsic coagulation pathway. The sponge/ powder demonstrated superior hemostatic capacity to commercial gauze, gelatin sponge, Yunnan Baiyao, and chitosan hemostatic powder in rat tail amputation, liver superficial injury, liver resection, and liver semi-perforation wound models. The sponge also presented robust anti-infection activity against methicillin-resistant Staphylococcus aureus and Escherichia coli. Additionally, the sponge showed low cytotoxicity, hemolysis activity, inflammation response, and systemic toxicity, demonstrating its favorable biocompatibility.
Zheng et al
Magnesium (Mg) has gained widespread recognition as a potential revolutionary orthopaedic biomaterial. However, whether the biodegradation of the Mg-based orthopaedic implants would pose a risk to patients with chronic kidney disease (CKD) remains undetermined as the kidney is a key organ regulating mineral homeostasis. A rat CKD model was established by a 5/6 subtotal nephrectomy approach, followed by intramedullary implantation of three types of pins: stainless steel, high pure Mg with high corrosion resistance, and the Mg-Sr-Zn alloy with a fast degradation rate. The long-term biosafety of the biodegradable Mg or its alloys as orthopaedic implants were systematically evaluated. During an experimental period of 12 weeks, the implantation did not result in a substantial rise of Mg ion concentration in serum or major organs such as hearts, livers, spleens, lungs, or kidneys. No pathological changes were observed in organs using various histological techniques. No significantly increased iNOS-positive cells or apoptotic cells in these organs were identified. The biodegradable Mg or its alloys as orthopaedic implants did not pose an extra health risk to CKD rats at long-term follow-up, suggesting that these biodegradable orthopaedic devices might be suitable for most target populations, including patients with CKD.
Chen et al
Literature on osteoimmunology has demonstrated that macrophages have a great influence on biomaterial-induced bone formation. However, there are almost no reports clarifying the osteo-immunomodulatory capacity of macrophage-derived extracellular vesicles (EVs). This study comprehensively investigated the effects of EVs derived from macrophages treated with biphasic calcium phosphate (BCP) ceramics (BEVs) on vital events associated with BCP-induced bone formation such as immune response, angiogenesis, and osteogenesis. It was found that compared with EVs derived from macrophages alone (control, CEVs), BEVs preferentially promoted macrophage polarization towards a wound-healing M2 phenotype, enhanced migration, angiogenic differentiation, and tube formation of human umbilical vein endothelial cells (HUVECs), and induced osteogenic differentiation of mesenchymal stem cells (MSCs). Analysis of 15 differentially expressed microRNAs (DEMs) related to immune, angiogenesis, and osteogenesis suggested that BEVs exhibited good immunomodulatory, pro-angiogenic, and pro-osteogenic abilities, which might be attributed to their specific miRNA cargos. These findings not only deepen our understanding of biomaterial-mediated osteoinduction, but also suggest that EVs derived from biomaterial-treated macrophages hold great promise as therapeutic agents with desired immunomodulatory capacity for bone regeneration.
Amin et al
Intro: Multiaxial filament winding is an additive manufacturing technique used extensively in large industrial and military manufacturing yet unexplored for biomedical uses. This study adapts filament winding to biomanufacture scalable, strong, three-dimensional microfiber (3DMF) medical device implants for potential orthopedic applications. 
 Methods: Polylactide, polydioxanone, or nanocellulose microfiber filaments were wound through a collagen "resin" bath to create organized, stable orthobiologic implants, which are sized for common ligament (e.g., anterior cruciate ligament) and tendon (e.g., rotator cuff) injuries and can be manufactured at industrial scale using a small footprint, economical, high-output benchtop system. Ethylene oxide or electron beam sterilized 3DMF samples were analyzed by scanning electron microscopy (SEM), underwent ASTM1635-based degradation testing, tensile testing, ISO 10993-based cytocompatibility, and biocompatibility testing, quantified for human platelet-rich plasma (PRP) absorption kinetics, and examined for adhesion of bioceramics and lyophilized collagen after coating. 
 Results: 3DMF implants had consistent fiber size and high alignment by SEM. Negligible mass and strength loss were noted over 4 months in culture. 3DMF implants initially exceeded 1,000 N hydrated tensile strength and retained over 70% strength through 4 months in culture, significantly stronger than conventionally produced implants made by fused fiber deposition 3D printing. 3DMF implants absorbed over 3x their weight in PRP within 5 minutes, were cytocompatible and biocompatible, and could readily bind tricalcium phosphate and calcium carbonate coatings discretely on implant ends for further orthobiologic material functionalization. The additive manufacturing process further enabled engineering implants with suture-shuttling passages for facile arthroscopic surgical delivery. 
 Conclusion and Clinical Significance: This accessible, facile, economical, and rapid microfiber manufacturing platform presents a new method to engineer high-strength, flexible, low-cost, bio-based implants for orthopedic and extended medical device applications.
Zhou et al
As the structural basis of connective and load-bearing tissues, collagen fibers with orientation play an important role in the mechanical properties and physiological and biochemical functions of the tissues, but viable methods for preparing scaffolds with highly oriented collagenous structure still need to be further studied. In this study, pure collagen was used as printing ink to 3D printing. Harnessing oriented collagen fiber structure by 3D printing for promoting mechanical and osteogenic properties of scaffolds. The scaffolds with different printed angles and thicknesses were prepared to fit the bone defect site and realize personalized customization. The orientation assembly of collagen fibers was promoted by shear force action of 3D printing, the regular arrangement of collagen fibers and stabilization of fiber structure were promoted by pH adjustment and glutaraldehyde cross-linking, and the collagen fibers were mineralized by cyclic mineralization method. The microscopic morphology of fiber arrangement in the scaffolds were investigated by scanning electron microscopy. Results demonstrated that collagen fibers were changed from non-oriented to oriented after 3D printing. And the tensile modulus of the scaffolds with oriented collagen fibers was nine times higher than that of the scaffolds with non-oriented fibers. Moreover, the effects of oriented collagen fibers on the proliferation, differentiation and mineralization of MC3T3-E1 cells were studied by CCK-8 assay, live/dead cell staining, alkaline phosphatase activity test, and Alizarin red staining. The results indicated that cell proliferation, differentiation and mineralization were significantly promoted by oriented collagen fibers, and the cells proliferated directionally in the direction of the fibers. Taken together, mineralized collagen fiber scaffolds with oriented collagen fibers have great potential in bone tissue engineering applications.
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Lizhen Zheng et al 2024 Biomed. Mater.
Magnesium (Mg) has gained widespread recognition as a potential revolutionary orthopaedic biomaterial. However, whether the biodegradation of the Mg-based orthopaedic implants would pose a risk to patients with chronic kidney disease (CKD) remains undetermined as the kidney is a key organ regulating mineral homeostasis. A rat CKD model was established by a 5/6 subtotal nephrectomy approach, followed by intramedullary implantation of three types of pins: stainless steel, high pure Mg with high corrosion resistance, and the Mg-Sr-Zn alloy with a fast degradation rate. The long-term biosafety of the biodegradable Mg or its alloys as orthopaedic implants were systematically evaluated. During an experimental period of 12 weeks, the implantation did not result in a substantial rise of Mg ion concentration in serum or major organs such as hearts, livers, spleens, lungs, or kidneys. No pathological changes were observed in organs using various histological techniques. No significantly increased iNOS-positive cells or apoptotic cells in these organs were identified. The biodegradable Mg or its alloys as orthopaedic implants did not pose an extra health risk to CKD rats at long-term follow-up, suggesting that these biodegradable orthopaedic devices might be suitable for most target populations, including patients with CKD.
Hideo Saotome et al 2024 Biomed. Mater.
The alignment of each cell in human myocardium is considered critical for the efficient movement of cardiac tissue. We investigated 96-well microstripe-patterned plates to align human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CMs), which resemble fetal myocardium. The aligned CMs (ACMs) cultured on the microstripe-patterned plates exhibited pathology, motor function, gene expression, and drug response that more closely resembled those of adult cells than did unaligned CMs cultured on a flat plate (FCMs). We used these ACMs to evaluate drug side effects and efficacy, and to determine whether these were similar to adult-like responses. When CMs from patients with hypertrophic cardiomyopathy (HCMs) were seeded and cultured on the microstripe-patterned plates or layered on top of the ACMs, both sets of HCMs showed increased heart rate and synchronized contractions, indicating improved cardiac function. It is suggested that the ACMs could be used for drug screening as cells representative of adult-like cardiomyocytes and be transplanted in the form of a cell sheet for regenerative treatment of heart failure.
Andrea Souza et al 2024 Biomed. Mater.
3D (bio)printing technology has boosted the advancement of the biomedical field. However, tissue engineering is in its infancy and (bio)printing biomimetic constructions for tissue formation in vitro is still a default. As a new methodology to improve in vitro studies, we suggest the use of a cross-linkable aqueous support bath to pattern the characteristics of the scaffolds during the 3D printing process. Using fluid-phase, different molecules can be added to specific locations of the substrate promoting cell behaviour guidance and compartmentalization. Moreover, mechanical aspects can be customized by changing the type or concentration of the solution in which the (bio)printing is acquired. In this study, we first assessed different formulations of alginate/gelatin to improve cell colonization in our printings. On formulations with lower gelatin content, the U2OS cells increased 2.83 times the cell growth. In addition, the alginate-gelatin hydrogel presented a good printability in both air and fluid-phase, however the fluid-phase printings showed better printing fidelity as it diminished the collapsing and the spreading of the hydrogel strand. Next, the fluid-phase methodology was used to guide cell colonization in our printings. First, different stiffness were created by crosslinking the hydrogel with different concentrations of CaCl2 during the printing process. As a result, the U2OS cells were compartmentalized on the stiffer parts of the printings. In addition, using fluid-phase to add RGD molecules to specific parts of the hydrogel has also promoted guidance on cell growth. Finally, our results showed that by combining stiffer alginate-gelatin hydrogel with RGD increasing concentrations we can create a synergetic effect and boost cell growth by up to 3.17-fold.This work presents a new printing process for tailoring multiple parameters in hydrogel substrates by using fluid-phase to generate a more faithful replication of the in vivo environment.
Xiaoming Liu et al 2024 Biomed. Mater. 19 042004
In the field of medicine, we often brave the unknown like interstellar explorers, especially when confronting the formidable opponent of hepatocellular carcinoma (HCC). The global burden of HCC remains significant, with suboptimal treatment outcomes necessitating the urgent development of novel drugs and treatments. While various treatments for liver cancer, such as immunotherapy and targeted therapy, have emerged in recent years, improving their transport and therapeutic efficiency, controlling their targeting and release, and mitigating their adverse effects remains challenging. However, just as we grope through the darkness, a glimmer of light emerges—nanotechnology. Recently, nanotechnology has attracted attention because it can increase the local drug concentration in tumors, reduce systemic toxicity, and has the potential to enhance the effectiveness of precision therapy for HCC. However, there are also some challenges hindering the clinical translation of drug-loaded nanoparticles (NPs). Just as interstellar explorers must overcome interstellar dust, we too must overcome various obstacles. In future researches, the design and development of nanodelivery systems for novel drugs treating HCC should be the first attention. Moreover, researchers should focus on the active targeting design of various NPs. The combination of the interventional therapies and drug-loaded NPs will greatly advance the process of precision HCC therapy.
Yinsheng Wu et al 2024 Biomed. Mater. 19 045011
The purpose of this study was to construct a rutin-controlled release system on the surface of Ti substrates and investigate its effects on osteogenesis and osseointegration on the surface of implants. The base layer, polyethylenimine (PEI), was immobilised on a titanium substrate. Then, hyaluronic acid (HA)/chitosan (CS)-rutin (RT) multilayer films were assembled on the PEI using layer-by-layer (LBL) assembly technology. We used scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy and contact angle measurements to examine all Ti samples. The drug release test of rutin was also carried out to detect the slow-release performance. The osteogenic abilities of the samples were evaluated by experiments on an osteoporosis rat model and MC3T3-E1 cells. The results (SEM, FTIR and contact angle measurements) all confirmed that the PEI substrate layer and HA/CS-RT multilayer film were effectively immobilised on titanium. The drug release test revealed that a rutin controlled release mechanism had been successfully established. Furthermore, the in vitro data revealed that osteoblasts on the coated titanium matrix had greater adhesion, proliferation, and differentiation capacity than the osteoblasts on the pure titanium surface. When MC3T3-E1 cells were exposed to H2O2-induced oxidative stress in vitro, cell-based tests revealed great tolerance and increased osteogenic potential on HA/CS-RT substrates. We also found that the HA/CS-RT coating significantly increased the new bone mass around the implant. The LBL-deposited HA/CS-RT multilayer coating on the titanium base surface established an excellent rutin-controlled release system, which significantly improved osseointegration and promoted osteogenesis under oxidative stress conditions, suggesting a new implant therapy strategy for patients with osteoporosis.
Haiyu Yu et al 2024 Biomed. Mater. 19 042002
Porous tantalum scaffolds offer a high degree of biocompatibility and have a low friction coefficient. In addition, their biomimetic porous structure and mechanical properties, which closely resemble human bone tissue, make them a popular area of research in the field of bone defect repair. With the rapid advancement of additive manufacturing, 3D-printed porous tantalum scaffolds have increasingly emerged in recent years, offering exceptional design flexibility, as well as facilitating the fabrication of intricate geometries and complex pore structures that similar to human anatomy. This review provides a comprehensive description of the techniques, procedures, and specific parameters involved in the 3D printing of porous tantalum scaffolds. Concurrently, the review provides a summary of the mechanical properties, osteogenesis and antibacterial properties of porous tantalum scaffolds. The use of surface modification techniques and the drug carriers can enhance the characteristics of porous tantalum scaffolds. Accordingly, the review discusses the application of these porous tantalum materials in clinical settings. Multiple studies have demonstrated that 3D-printed porous tantalum scaffolds exhibit exceptional corrosion resistance, biocompatibility, and osteogenic properties. As a result, they are considered highly suitable biomaterials for repairing bone defects. Despite the rapid development of 3D-printed porous tantalum scaffolds, they still encounter challenges and issues when used as bone defect implants in clinical applications. Ultimately, a concise overview of the primary challenges faced by 3D-printed porous tantalum scaffolds is offered, and corresponding insights to promote further exploration and advancement in this domain are presented.
Zhihui Chen et al 2024 Biomed. Mater. 19 045006
Cervical carcinoma persists as a major global public health burden. While conventional therapeutic modalities inevitably cause ablation of adjacent non-tumorous tissues, photodynamic therapy (PDT) offers a targeted cytotoxic strategy through a photosensitizing agent (PS). However, the hydrophobicity and lack of selective accumulation of promising PS compounds such as zinc(II) phthalocyanine (ZnPc) impedes their clinical translation as standalone agents. The present study sought to incorporate ZnPc within double-layer hollow mesoporous silica nanoparticles (DHMSN) as nanocarriers to enhance aqueous dispersibility and tumor specificity. Owing to their compartmentalized design, the hollow mesoporous silica nanoparticles (HMSN) demonstrated enhanced ultrasonic imaging contrast. Combined with the vaporization of the perfluorocarbon perfluoropentane (PFP), the HMSN-encapsulated ZnPc enabled real-time ultrasound monitoring of PDT treatment. In vivo, the innate thermal energy induced vaporization of the DHMSN-carried PFP to significantly amplify ultrasound signals from the tumor site. Results demonstrated biocompatibility, efficient PFP microbubble generation, and robust photocatalytic activity. Collectively, this investigation establishes ultrasound-guided PDT utilizing multi-layer HMSN as a targeted therapeutic strategy for cervical malignancies with mitigated toxicity.
Laura Rodríguez-Mandujano et al 2024 Biomed. Mater. 19 045005
Collagen type I is a material widely used for 3D cell culture and tissue engineering. Different architectures, such as gels, sponges, membranes, and nanofibers, can be fabricated with it. In collagen hydrogels, the formation of fibrils and fibers depends on various parameters, such as the source of collagen, pH, temperature, concentration, age, etc. In this work, we study the fibrillogenesis process in collagen type I hydrogels with different types of microbeads embedded, using optical techniques such as turbidity assay and confocal reflectance microscopy. We observe that microbeads embedded in the collagen matrix hydrogels modify the fibrillogenesis. Our results show that carboxylated fluorescent microbeads accelerate 3.6 times the gelation, while silica microbeads slow down the formation of collagen fibrils by a factor of 1.9, both compared to pure collagen hydrogels. Our observations suggest that carboxylate microbeads act as nucleation sites and the early collagen fibrils bind to the microbeads.
Zhijun Zhang et al 2024 Biomed. Mater. 19 045002
The decellularized matrix has a great potential for tissue remodeling and regeneration; however, decellularization could induce host immune rejection due to incomplete cell removal or detergent residues, thereby posing significant challenges for its clinical application. Therefore, the selection of an appropriate detergent concentration, further optimization of tissue decellularization technique, increased of biosafety in decellularized tissues, and reduction of tissue damage during the decellularization procedures are pivotal issues that need to be investigated. In this study, we tested several conditions and determined that 0.1% Sodium dodecyl sulfate and three decellularization cycles were the optimal conditions for decellularization of pulp tissue. Decellularization efficiency was calculated and the preparation protocol for dental pulp decellularization matrix (DPDM) was further optimized. To characterize the optimized DPDM, the microstructure, odontogenesis-related protein and fiber content were evaluated. Our results showed that the properties of optimized DPDM were superior to those of the non-optimized matrix. We also performed the 4D-Label-free quantitative proteomic analysis of DPDM and demonstrated the preservation of proteins from the natural pulp. This study provides a optimized protocol for the potential application of DPDM in pulp regeneration.
Eliza Ranjit et al 2024 Biomed. Mater. 19 035036
Wool derived keratin, due to its demonstrated ability to promote bone formation, has been suggested as a potential bioactive material for implant surfaces. The aim of this study was to assess the effects of keratin-coated titanium on osteoblast function in vitro and bone healing in vivo. Keratin-coated titanium surfaces were fabricated via solvent casting and molecular grafting. The effect of these surfaces on the attachment, osteogenic gene, and osteogenic protein expression of MG-63 osteoblast-like cells were quantified in vitro. The effect of these keratin-modified surfaces on bone healing over three weeks using an intraosseous calvaria defect was assessed in rodents. Keratin coating did not affect MG-63 proliferation or viability, but enhanced osteopontin, osteocalcin and bone morphogenetic expression in vitro. Histological analysis of recovered calvaria specimens showed osseous defects covered with keratin-coated titanium had a higher percentage of new bone area two weeks after implantation compared to that in defects covered with titanium alone. The keratin-coated surfaces were biocompatible and stimulated osteogenic expression in adherent MG-63 osteoblasts. Furthermore, a pilot preclinical study in rodents suggested keratin may stimulate earlier intraosseous calvaria bone healing.