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.
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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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Wenjing Yin et al 2024 Biomed. Mater. 19 032002
Tiancheng Li et al 2023 Biomed. Mater. 18 052004
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.
Yas Maghdouri-White et al 2021 Biomed. Mater. 16 025025
Approximately 800, 000 surgical repairs are performed annually in the U.S. for debilitating injuries to ligaments and tendons of the foot, ankle, knee, wrist, elbow and shoulder, presenting a significant healthcare burden. To overcome current treatment shortcomings and advance the treatment of tendon and ligament injuries, we have developed a novel electrospun Tissue ENgineered Device (TEND), comprised of type I collagen and poly(D,L-lactide) (PDLLA) solubilized in a benign solvent, dimethyl sulfoxide (DMSO). TEND fiber alignment, diameter and porosity were engineered to enhance cell infiltration leading to promote tissue integration and functional remodeling while providing biomechanical stability. TEND rapidly adsorbs blood and platelet-rich-plasma (PRP), and gradually releases growth factors over two weeks. TEND further supported cellular alignment and upregulation of tenogenic genes from clinically relevant human stem cells within three days of culture. TEND implanted in a rabbit Achilles tendon injury model showed new in situ tissue generation, maturation, and remodeling of dense, regularly oriented connective tissue in vivo. In all, TEND's organized microfibers, biological fluid and cell compatibility, strength and biocompatiblility make significant progress towards clinically translating electrospun collagen-based medical devices for improving the clinical outcomes of tendon injuries.
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.
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.
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.
Aysel Koç-Demir et al 2024 Biomed. Mater. 19 035027
The development of new three-dimensional biomaterials with advanced versatile properties is critical to the success of tissue engineering (TE) applications. Here, (a) bioactive decellularized tendon extracellular matrix (dECM) with a sol-gel transition feature at physiological temperature, (b) halloysite nanotubes (HNT) with known mechanical properties and bioactivity, and (c) magnetic nanoparticles (MNP) with superparamagnetic and osteogenic properties were combined to develop a new scaffold that could be used in prospective bone TE applications. Deposition of MNPs on HNTs resulted in magnetic nanostructures without agglomeration of MNPs. A completely cell-free, collagen- and glycosaminoglycan- rich dECM was obtained and characterized. dECM-based scaffolds incorporated with 1%, 2% and 4% MNP-HNT were analysed for their physical, chemical, and in vitro biological properties. Fourier-transform infrared spectroscopy, x-ray powder diffractometry and vibrating sample magnetometry analyses confirmed the presence of dECM, HNT and MNP in all scaffold types. The capacity to form apatite layer upon incubation in simulated body fluid revealed that dECM-MNP-HNT is a bioactive material. Combining dECM with MNP-HNT improved the thermal stability and compressive strength of the macroporous scaffolds upto 2% MNP-HNT. In vitro cytotoxicity and hemolysis experiments showed that the scaffolds were essentially biocompatible. Human bone marrow mesenchymal stem cells adhered and proliferated well on the macroporous constructs containing 1% and 2% MNP-HNT; and remained metabolically active for at least 21 d in vitro. Collectively, the findings support the idea that magnetic nanocomposite dECM scaffolds containing MNP-HNT could be a potential template for TE applications.
Paulo André Marinho et al 2024 Biomed. Mater. 19 025041
In vitro hair follicle (HF) models are currently limited to ex vivo HF organ cultures (HFOCs) or 2D models that are of low availability and do not reproduce the architecture or behavior of the hair, leading to poor screening systems. To resolve this issue, we developed a technology for the construction of a human in vitro hair construct based on the assemblage of different types of cells present in the hair organ. First, we demonstrated that epithelial cells, when isolated in vitro, have similar genetic signatures regardless of their dissection site, and their trichogenic potential is dependent on the culture conditions. Then, using cell aggregation techniques, 3D spheres of dermal papilla (DP) were constructed, and subsequently, epithelial cells were added, enabling the production and organization of keratins in hair, similar to what is seen in vivo. These reconstructed tissues resulted in the following hair compartments: K71 (inner root-sheath), K85 (matrix region), K75 (companion layer), and vimentin (DP). Furthermore, the new hair model was able to elongate similarly to ex vivo HFOC, resulting in a shaft-like shape several hundred micrometers in length. As expected, when the model was exposed to hair growth enhancers, such as ginseng extract, or inhibitors, such as TGF-B-1, significant effects similar to those in vivo were observed. Moreover, when transplanted into skin biopsies, the new constructs showed signs of integration and hair bud generation. Owing to its simplicity and scalability, this model fully enables high throughput screening of molecules, which allows understanding of the mechanism by which new actives treat hair loss, finding optimal concentrations, and determining the synergy and antagonism among different raw materials. Therefore, this model could be a starting point for applying regenerative medicine approaches to treat hair loss.
Idil Uysal et al 2024 Biomed. Mater. 19 022004
As a thermoplastic and bioinert polymer, polyether ether ketone (PEEK) serves as spine implants, femoral stems, cranial implants, and joint arthroplasty implants due to its mechanical properties resembling the cortical bone, chemical stability, and radiolucency. Although there are standards and antibiotic treatments for infection control during and after surgery, the infection risk is lowered but can not be eliminated. The antibacterial properties of PEEK implants should be improved to provide better infection control. This review includes the strategies for enhancing the antibacterial properties of PEEK in four categories: immobilization of functional materials and functional groups, forming nanocomposites, changing surface topography, and coating with antibacterial material. The measuring methods of antibacterial properties of the current studies of PEEK are explained in detail under quantitative, qualitative, and in vivo methods. The mechanisms of bacterial inhibition by reactive oxygen species generation, contact killing, trap killing, and limited bacterial adhesion on hydrophobic surfaces are explained with corresponding antibacterial compounds or techniques. The prospective analysis of the current studies is done, and dual systems combining osteogenic and antibacterial agents immobilized on the surface of PEEK are found the promising solution for a better implant design.
Sreypich Say et al 2024 Biomed. Mater. 19 035012
In post-adhesion surgery, there is a clinical need for anti-adhesion membranes specifically designed for the liver, given the limited efficacy of current commercial products. To address this demand, we present a membrane suitable for liver surgery applications, fabricated through the modification of decellularized porcine pericardium with 20 KDa hexaglycerol octa (succinimidyloxyglutaryl) polyoxyethylene (8-arm PEGNHS). We also developed an optimized modification procedure to produce a high-performance anti-adhesion barrier. The modified membrane significantly inhibited fibroblast cell adherence while maintaining minimal levels of inflammation. By optimizing the modification ratio, we successfully controlled post-adhesion formation. Notably, the 8-arm PEG-modified pericardium with a molar ratio of 5 exhibited the ability to effectively prevent post-adhesion formation on the liver compared to both the control and Seprafilm®, with a low adhesion score of 0.5 out of 3.0. Histological analysis further confirmed its potential for easy separation. Furthermore, the membrane demonstrated regenerative capabilities, as evidenced by the proliferation of mesothelial cells on its surface, endowing anti-adhesion properties between the abdominal wall and liver. These findings highlight the membrane's potential as a reliable barrier for repeated liver resection procedures that require the removal of the membrane multiple times.
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Wenming Yin et al 2024 Biomed. Mater. 19 035041
It is well-established that multi-scale porous scaffolds can guide axonal growth and facilitate functional restoration after spinal cord injury (SCI). In this study, we developed a novel mussel shell-inspired conductive scaffold for SCI repair with ease of production, multi-scale porous structure, high flexibility, and excellent biocompatibility. By utilizing the reducing properties of polydopamine, non-conductive graphene oxide (GO) was converted into conductive reduced graphene oxide (rGO) and crosslinked in situ within the mussel shells. In vitro experiments confirmed that this multi-scale porous Shell@PDA-GO could serve as structural cues for enhancing cell adhesion, differentiation, and maturation, as well as promoting the electrophysiological development of hippocampal neurons. After transplantation at the injury sites, the Shell@PDA-GO provided a pro-regenerative microenvironment, promoting endogenous neurogenesis, triggering neovascularization, and relieving glial fibrosis formation. Interestingly, the Shell@PDA-GO could induce the release of endogenous growth factors (NGF and NT-3), resulting in the complete regeneration of nerve fibers at 12 weeks. This work provides a feasible strategy for the exploration of conductive multi-scale patterned scaffold to repair SCI.
Zeqi Liu et al 2024 Biomed. Mater. 19 032005
Spinal cord injury (SCI) is a devastating neurological disorder, leading to loss of motor or somatosensory function, which is the most challenging worldwide medical problem. Re-establishment of intact neural circuits is the basis of spinal cord regeneration. Considering the crucial role of electrical signals in the nervous system, electroactive bioscaffolds have been widely developed for SCI repair. They can produce conductive pathways and a pro-regenerative microenvironment at the lesion site similar to that of the natural spinal cord, leading to neuronal regeneration and axonal growth, and functionally reactivating the damaged neural circuits. In this review, we first demonstrate the pathophysiological characteristics induced by SCI. Then, the crucial role of electrical signals in SCI repair is introduced. Based on a comprehensive analysis of these characteristics, recent advances in the electroactive bioscaffolds for SCI repair are summarized, focusing on both the conductive bioscaffolds and piezoelectric bioscaffolds, used independently or in combination with external electronic stimulation. Finally, thoughts on challenges and opportunities that may shape the future of bioscaffolds in SCI repair are concluded.
Yunda Han et al 2024 Biomed. Mater. 19 035042
Three-dimensional (3D) printing has emerged as a transformative technology for tissue engineering, enabling the production of structures that closely emulate the intricate architecture and mechanical properties of native biological tissues. However, the fabrication of complex microstructures with high accuracy using biocompatible, degradable thermoplastic elastomers poses significant technical obstacles. This is primarily due to the inherent soft-matter nature of such materials, which complicates real-time control of micro-squeezing, resulting in low fidelity or even failure. In this study, we employ Poly (L-lactide-co--caprolactone) (PLCL) as a model material and introduce a novel framework for high-precision 3D printing based on the material plasticization process. This approach significantly enhances the dynamic responsiveness of the start-stop transition during printing, thereby reducing harmful errors by up to 93%. Leveraging this enhanced material, we have efficiently fabricated arrays of multi-branched vascular scaffolds that exhibit exceptional morphological fidelity and possess elastic moduli that faithfully approximate the physiological modulus spectrum of native blood vessels, ranging from 2.5 to 45 MPa. The methodology we propose for the compatibilization and modification of elastomeric materials addresses the challenge of real-time precision control, representing a significant advancement in the domain of melt polymer 3D printing. This innovation holds considerable promise for the creation of detailed multi-branch vascular scaffolds and other sophisticated organotypic structures critical to advancing tissue engineering and regenerative medicine.
Kimaya Meher et al 2024 Biomed. Mater. 19 035039
Fabrication of gold nanoparticles (GNPs) with phytochemicals is an emerging green nanotechnology approach with therapeutic implications. Garlic, known for its culinary and medicinal properties, has been extensively investigated for its anticancer properties. Here, we report a method to substantially enhance the antiproliferative potency of garlic by functionalizing its phytochemicals to GNPs and demonstrate a possible mechanism of action of these nanoparticles in the triple-negative breast cancer cell line, MDA-MB-231. Garlic gold nanoparticles (As-GNPs) were synthesized using garlic extract (As-EX) and gold chloride and characterized using a variety of spectroscopy techniques, and transmission electron microscopy (TEM). Compared to As-EX, which has a negligible effect on the viability of the cells, As-GNPs inhibited cell viability with an IC50 of 0.310 ± 0.04 mg ml−1 and strongly inhibited the clonogenic and migratory propensities of these cells. As indicated by TEM, the As-GNPs entered the cells via endocytosis and dispersed in the cellular milieu. Since tubulin, the protein involved in cell division, is a verified target for several antiproliferative drugs, we next examined whether the As-GNPs interact with this protein. The As-GNPs showed concentration-dependent binding to purified tubulin, slightly but consistently perturbing its secondary helical integritywithout grossly damaging the tertiary structure of the protein or the net polymer mass of the microtubules, as indicated by a tryptophan-quenching assay, far UV-circular dichroism spectroscopy, anilinonaphthalene sulfonate-binding assay, and polymer mass analysis, respectively. In cells, As-GNPs killed the cancer cells without cell cycle arrest, as evidenced by flow cytometry.
Febina Josephraj et al 2024 Biomed. Mater. 19 035040
Dental cement residues exacerbate peri-implant tissue irritation and peri-implantitis. The present study aims to evaluate the cytotoxicity, physiochemical, optical, and rheological properties of carbon quantum dots (CQDs) impregnated glass ionomer cement (GIC). Surface passivated fluorescent CQDs were synthesized using citric acid via thermal decomposition and blended with GIC. Characterization studies and rheological measurements were made to evaluate their performance. 3D-printed dental implant models cemented with GIC and GIC-CQD were compared to analyze excess cement residues. MTT assay was performed with human dental pulp stem cells (hDPSCs) and statistically analyzed using ANOVA and Tukey's test. CQDs with a particle dimension of ∼2 nm were synthesized. The amorphous property of GIC-CQD was confirmed through XRD. The fluorescence properties of GIC-CQD showed three times higher emission intensity than conventional GIC. GIC-CQD attained maturation with a setting time extended by 64 s than GIC. Cement residue of size 2 mm was detected with a UV light excitation at a distance between 5 to 10 cm. Biocompatibility at 0.125 mg ml−1 dilution concentrations of GIC-CQD showed viability greater than 80% to hDPSCs. For the first time, we report that CQDs-impregnated GIC is a unique and cost-effective strategy for in-situ detection of excess cement rapidly using a hand-held device. A novel in-situ rapid detection method enables the dentist to identify residual cement of size less than 2 mm during the implantation. Therefore, GIC-CQD would replace conventional GIC and help in the prevention of peri-implant diseases.
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Zeqi Liu et al 2024 Biomed. Mater. 19 032005
Spinal cord injury (SCI) is a devastating neurological disorder, leading to loss of motor or somatosensory function, which is the most challenging worldwide medical problem. Re-establishment of intact neural circuits is the basis of spinal cord regeneration. Considering the crucial role of electrical signals in the nervous system, electroactive bioscaffolds have been widely developed for SCI repair. They can produce conductive pathways and a pro-regenerative microenvironment at the lesion site similar to that of the natural spinal cord, leading to neuronal regeneration and axonal growth, and functionally reactivating the damaged neural circuits. In this review, we first demonstrate the pathophysiological characteristics induced by SCI. Then, the crucial role of electrical signals in SCI repair is introduced. Based on a comprehensive analysis of these characteristics, recent advances in the electroactive bioscaffolds for SCI repair are summarized, focusing on both the conductive bioscaffolds and piezoelectric bioscaffolds, used independently or in combination with external electronic stimulation. Finally, thoughts on challenges and opportunities that may shape the future of bioscaffolds in SCI repair are concluded.
Ritu Raj et al 2024 Biomed. Mater. 19 032004
Electrospinning technique converts polymeric solutions into nanoscale fibers using an electric field and can be used for various biomedical and clinical applications. Extracellular vesicles (EVs) are cell-derived small lipid vesicles enriched with biological cargo (proteins and nucleic acids) potential therapeutic applications. In this review, we discuss extending the scope of electrospinning by incorporating stem cell-derived EVs, particularly exosomes, into nanofibers for their effective delivery to target tissues. The parameters used during the electrospinning of biopolymers limit the stability and functional properties of cellular products. However, with careful consideration of process requirements, these can significantly improve stability, leading to longevity, effectiveness, and sustained and localized release. Electrospun nanofibers are known to encapsulate or surface-adsorb biological payloads such as therapeutic EVs, proteins, enzymes, and nucleic acids. Small EVs, specifically exosomes, have recently attracted the attention of researchers working on regeneration and tissue engineering because of their broad distribution and enormous potential as therapeutic agents. This review focuses on current developments in nanofibers for delivering therapeutic cargo molecules, with a special emphasis on exosomes. It also suggests prospective approaches that can be adapted to safely combine these two nanoscale systems and exponentially enhance their benefits in tissue engineering, medical device coating, and drug delivery applications.
Tanima Dey et al 2024 Biomed. Mater. 19 032003
In terms of biomedical tools, nanodiamonds (ND) are a more recent innovation. Their size typically ranges between 4 to 100 nm. ND are produced via a variety of methods and are known for their physical toughness, durability, and chemical stability. Studies have revealed that surface modifications and functionalization have a significant influence on the optical and electrical properties of the nanomaterial. Consequently, surface functional groups of NDs have applications in a variety of domains, including drug administration, gene delivery, immunotherapy for cancer treatment, and bio-imaging to diagnose cancer. Additionally, their biocompatibility is a critical requisite for their in vivo and in vitro interventions. This review delves into these aspects and focuses on the recent advances in surface modification strategies of NDs for various biomedical applications surrounding cancer diagnosis and treatment. Furthermore, the prognosis of its clinical translation has also been discussed.
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.
Sanchita Tripathy et al 2024 Biomed. Mater. 19 032001
Sodium nitroprusside (SNP), U.S approved drug has been used in clinical emergency as a hypertensive drug for more than a decade. It is well established for its various biomedical applications such as angiogenesis, wound healing, neurological disorders including anti-microbial applications etc. Apart from that, SNP have been considered as excellent biomedical materials for its use as anti-cancer agent because of its behavior as NO-donor. Recent reports suggest that incorporation of metals in SNP/encapsulation of SNP in metal nanoparticles (metal nitroprusside analogues) shows better therapeutic anti-cancer activity. Although there are numerous reports available regarding the biological applications of SNP and metal-based SNP analogue nanoparticles, unfortunately there is not a single comprehensive review which highlights the anti-cancer activity of SNP and its derivative metal analogues in detail along with the future perspective. To this end, the present review article focuses the recent development of anti-cancer activity of SNP and metal-based SNP analogues, their plausible mechanism of action, current status. Furthermore, the future perspectives and challenges of these biomedical materials are also discussed. Overall, this review article represents a new perspective in the area of cancer nanomedicine that will attract a wider spectrum of scientific community.
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Rodríguez-Mandujano et al
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.
Bihari et al
Bone fracture plates are usually made from steel or titanium, which are much stiffer than 
cortical bone. This may cause bone "stress shielding" (i.e., bone resorption leading to plate 
loosening) and delayed fracture healing (i.e., fracture motion is less than needed to stimulate 
callus formation at the fracture). Thus, the authors previously designed, fabricated, and 
mechanically tested novel "hybrid" composites made from inorganic and organic materials as 
potential bone fracture plates that are more flexible to reduce these negative effects. This is the 
first study to measure the cytotoxicity of these composites via the survival of rat cells. Cubes 
of carbon fiber/flax fiber/epoxy and glass fiber/flax fiber/epoxy had better cell survival vs. 
Kevlar fiber/flax fiber/epoxy (57% and 58% vs. 50%). Layers and powders made of carbon 
fiber/epoxy and glass fiber/epoxy had higher cell survival than Kevlar fiber/epoxy (96-100% 
and 100% vs. 39-90%). The presence of flax fibers usually decreased cell survival. Thus, 
carbon and glass fiber composites (with or without flax fibers), but not Kevlar fiber composites
(with or without flax fibers), may potentially be used for bone fracture plates.
Kim et al
This study investigated the effectiveness of bone regeneration upon the application of leptin and osteolectin to a three-dimensional (3D) printed poly(ε-caprolactone) (PCL) scaffold. A fused deposition modeling 3D bioprinter was used to fabricate scaffolds with a diameter of 4.5 mm, a height of 0.5 mm, and a pore size of 420–520 nm using PCL (molecular weight: 43,000). After amination of the scaffold surface for leptin and osteolectin adhesion, the experimental groups were divided into the PCL scaffold (control), the aminated PCL (PCL/Amine) scaffold, the leptin-coated PCL (PCL/Leptin) scaffold, and the osteolectin-coated PCL (PCL/Osteo) scaffold. Next, the water-soluble tetrazolium salt-1 (WST-1) assay was used to assess cell viability. All groups exhibited cell viability rates of >100%. Female 7-week-old Sprague-Dawley rats were used for in vivo experiments. Calvarial defects were introduced on the rats' skulls using a 5.5 mm trephine bur. The rats were divided into the PCL (control), PCL/Leptin, and PCL/Osteo scaffold groups. The scaffolds were then inserted into the calvarial defect areas, and the rats were sacrificed after 8-weeks to analyze the defect area. Micro-CT analysis indicated that the leptin- and osteolectin-coated scaffolds exhibited significantly higher bone regeneration. Histological analysis revealed new bone and blood vessels in the calvarial defect area. These findings indicate that the 3D-printed PCL scaffold allows for patient-customized fabrication as well as the easy application of proteins like leptin and osteolectin. Moreover, leptin and osteolectin did not show cytotoxicity and exhibited higher bone regeneration potential than the existing scaffold.
Li et al
Anodized titania nanotubes have been considered as an effective coating for bone implants due to their ability to induce osteogenesis, but the mechanism is not fully understood. Our previous study indicated the potential role of autophagy in osteogenic regulation of nanotubular surface, whereas how the autophagy is activated remains unknown. In this study, we focused on the cell membrane curvature-sensing protein Bif-1 and its effect on the regulation of autophagy. Both autophagosome formation and autophagic flux are enhanced on the nanotubular surface, as indicated by LC3-II accumulation and p62 degradation. In the meanwhile, the Bif-1 was significantly upregulated, which contributed to autophagy activation and osteogenic differentiation through Beclin-1/PIK3C3 signaling pathway. In conclusion, these findings may provide deeper insight into the signaling transition from mechanical to biological across the cell membrane.
Gupta et al
Tissue adhesives offer a plethora of advantages in achieving efficient wound closure over conventional sutures and staples. Such materials are of great value, especially in cases where suturing could potentially damage tissues or compromise blood flow or in cases of hard-to-reach areas. Besides providing wound closure, the tissue adhesives must also facilitate wound healing. Previously, plasma-based tissue adhesives and similar bioinspired strategies have been utilized to aid in wound healing. Still, their application is constrained by factors such as high cost, diminished biocompatibility, prolonged gelation times, inadequate swelling, quick resorption, as well as short-term and inconsistent efficacy. To address these limitations, we report the development of a highly biocompatible and ultrafast-gelling tissue adhesive hydrogels. Freeze-dried platelet-rich plasma (PRP), heat-denatured freeze-dried platelet-poor plasma (PPP), and gelatin were utilized as the base matrix. Gelation was initiated by adding Tetrakis hydroxymethyl phosphonium chloride (THPC). The fabricated gels displayed rapid gelation (3-4 s), low swelling, increased proliferation, and migration against L929 cells and had porcine skin tissue adhesion strength similar to that of plasma-based commercial glue (Tisseel®).
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Laura Rodríguez-Mandujano et al 2024 Biomed. Mater.
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.
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.
Zhijun Zhang et al 2024 Biomed. Mater.
The decellularized matrixhas 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. Inthis study, we tested several conditions and determined that 0.1% Sodium dodecyl sulfate(SDS) 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 solid theoretical and experimental foundation for the potential application of DPDM in pulp regeneration.
Zhihui Chen et al 2024 Biomed. Mater.
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.
Chang Liu et al 2024 Biomed. Mater. 19 035028
In bone tissue engineering, the bone immunomodulatory properties of biomaterials are critical for bone regeneration, which is a synergistic process involving physiological activities like immune response, osteogenesis, and angiogenesis. The effect of the macrophage immune microenvironment on the osteogenesis and angiogenesis of various material extracts was examined in this experiment using Mg2+ and Nano-hydroxyapatite/collagen (nHAC) in both a single application and a combined form. This study in vitro revealed that the two compounds combined significantly inhibited the NF-κB signaling pathway and reduced the release of inflammatory factors from macrophages when compared with the extraction phase alone. Additionally, by contributing to the polarization of macrophages towards the M2 type, the combined effects of the two materials can significantly improve osteogenesis/angiogenesis. The results of in vivo experiments confirmed that Mg2+/nHAC significantly promoted bone regeneration and angiogenesis. This study offers a promising method for enhancing bone graft material osseointegration.
Aysel Koç-Demir et al 2024 Biomed. Mater. 19 035027
The development of new three-dimensional biomaterials with advanced versatile properties is critical to the success of tissue engineering (TE) applications. Here, (a) bioactive decellularized tendon extracellular matrix (dECM) with a sol-gel transition feature at physiological temperature, (b) halloysite nanotubes (HNT) with known mechanical properties and bioactivity, and (c) magnetic nanoparticles (MNP) with superparamagnetic and osteogenic properties were combined to develop a new scaffold that could be used in prospective bone TE applications. Deposition of MNPs on HNTs resulted in magnetic nanostructures without agglomeration of MNPs. A completely cell-free, collagen- and glycosaminoglycan- rich dECM was obtained and characterized. dECM-based scaffolds incorporated with 1%, 2% and 4% MNP-HNT were analysed for their physical, chemical, and in vitro biological properties. Fourier-transform infrared spectroscopy, x-ray powder diffractometry and vibrating sample magnetometry analyses confirmed the presence of dECM, HNT and MNP in all scaffold types. The capacity to form apatite layer upon incubation in simulated body fluid revealed that dECM-MNP-HNT is a bioactive material. Combining dECM with MNP-HNT improved the thermal stability and compressive strength of the macroporous scaffolds upto 2% MNP-HNT. In vitro cytotoxicity and hemolysis experiments showed that the scaffolds were essentially biocompatible. Human bone marrow mesenchymal stem cells adhered and proliferated well on the macroporous constructs containing 1% and 2% MNP-HNT; and remained metabolically active for at least 21 d in vitro. Collectively, the findings support the idea that magnetic nanocomposite dECM scaffolds containing MNP-HNT could be a potential template for TE applications.
Sophie Schweinitzer et al 2024 Biomed. Mater. 19 031001
Tissue-like constructs, intended for application in tissue engineering and regenerative medicine, can be produced by three-dimensional (3D) bioprinting of cells in hydrogels. It is essential that the viability and proliferation of the encapsulated cells can be reliably determined. Methods currently used to evaluate cell proliferation, such as quantification of DNA and measurement of metabolic activity, have been developed for application in 2D cultures and might not be suitable for bioinks. In this study, human fibroblasts were either cast or printed in gelatin methacryloyl (GelMA) or sodium alginate hydrogels and cell proliferation was assessed by AlamarBlue, PicoGreen and visual cell counts. Comparison of data extrapolated from standard curves generated from 2D cultures and 3D hydrogels showed potential inaccuracies. Moreover, there were pronounced discrepancies in cell numbers obtained from these assays; the different bioinks strongly influenced the outcomes. Overall, the results indicate that more than one method should be applied for better assessment of cell proliferation in bioinks.
Alexandra Jednorski et al 2024 Biomed. Mater. 19 035022
Cd0.3Pb0.7S (CdPbS) aqueous quantum dots (AQDs) made with 3-mercaptoproprionic acid (MPA) as a ligand have the advantages of emitting near-infrared light, well above 800 nm, that completely circumvents interference from tissue autofluorescence and have significant amounts of ligands for bioconjugation. However, retaining the right amount of MPA became a challenge when using CdPbS AQDs for bioimaging because retaining too much MPA could lead to significant nonspecific staining in cell imaging while insufficient MPA could cause AQDs instability in biological systems. Here we examined PEGylation (i.e. chemically linking amine-functionalized polyethylene glycol (PEG)) to modify MPA on the AQDs surface to improve AQDs stability and reduce nonspecific staining. In addition, for conjugation with antibodies, a bifunctional PEG with a carboxyl functionality was used to permit chemical linkage of a PEG to an antibody on the other end. It was found that performing PEGylation at the thiol concentration where the zeta potential becomes saturated stabilized the CdPbS AQDs suspension and reduced nonspecific binding to cells. Furthermore, with the bifunctional PEG, the CdPbS AQDs were conjugated with antibodies and the AQD-Ab conjugates were shown to stain cancer cells specifically against normal cells with a signal-to-noise ratio of 8.
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.
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.