Iron-, magnesium-, or zinc-based metal vessel stents support vessel expansion at the period early after implantation and degrade away after vascular reconstruction, eliminating the side effects due to the long stay of stent implants in the body and the risks of restenosis and neoatherosclerosis. However, emerging evidence has indicated that their degradation alters the vascular microenvironment and induces adaptive responses of surrounding vessel cells, especially vascular smooth muscle cells (VSMCs). VSMCs are highly flexible cells that actively alter their phenotype in response to the stenting, similarly to what they do during all stages of atherosclerosis pathology, which significantly influences stent performance. This Review discusses how biodegradable metal stents modify vascular conditions and how VSMCs respond to various chemical, biological, and physical signals attributable to stent implantation. The focus is placed on the phenotypic adaptation of VSMCs and the clinical complications, which highlight the importance of VSMC transformation in future stent design.

Model verification is a critical aspect of scientific accountability, transparency, and learning. Here, we demonstrate an application of a model verification approach for a molecular dynamics (MD) simulation, where the interactions between silica and silk protein were studied experimentally toward understanding biomineralization. Following the ten rules for credible modeling and simulation of biosciences as developed in Erdemir et al., the authors of the original paper collaborated with an external modeling group to verify the key findings of their original simulation model and to document this verification approach. The process resulted in successful replication of the key findings of the original model. Beyond verification, study of the model from a new perspective generated new insight into the basic assumptions. We discuss key learnings for how model validation processes can be improved more generally, specifically through improved documentation methods. We anticipate that this application of our protocol for model verification can be further replicated and improved to verify and validate other simulations.

The clinical treatment of infectious bone defects is difficult and time-consuming due to the coexistence of infection and bone defects, and the simultaneous control of infection and repair of bone defects is considered a promising therapy. In this study, a dual-drug delivery scaffold system was fabricated by the combination of a three-dimensional (3D) printed scaffold with hydrogel for infected bone defects repair. The 3D printed polycaprolactone scaffold was incorporated with biodegradable mesoporous silica nanoparticles containing the small molecular drug fingolimod (FTY720) to provide structural support and promote angiogenesis and osteogenesis. The vancomycin (Van)-loaded hydrogel was prepared from aldehyde hyaluronic acid (AHA) and carboxymethyl chitosan (NOCC) by the Schiff base reaction, which can fill the pores of the 3D-printed scaffold to produce a bifunctional composite scaffold. The in vitro results demonstrated that the composite scaffold had Van concentration-dependent antimicrobial properties. Furthermore, the FTY720-loaded composite scaffold demonstrated excellent biocompatibility, vascularization, and osteogenic ability in vitro. In the rat femoral defect model with bacterial infection, the dual-drug composite scaffold showed a better outcome in both infection control and bone regeneration compared to other groups. Therefore, the prepared bifunctional composite scaffold has potential application in the treatment of infected bone defects.

Spinal cord injury (SCI) causes severe motor or sensory damage that leads to long-term disabilities due to disruption of electrical conduction in neuronal pathways. Despite current clinical therapies being used to limit the propagation of cell or tissue damage, the need for neuroregenerative therapies remains. Conductive hydrogels have been considered a promising neuroregenerative therapy due to their ability to provide a pro-regenerative microenvironment and flexible structure, which conforms to a complex SCI lesion. Furthermore, their conductivity can be utilized for noninvasive electrical signaling in dictating neuronal cell behavior. However, the ability of hydrogels to guide directional axon growth to reach the distal end for complete nerve reconnection remains a critical challenge. In this Review, we highlight recent advances in conductive hydrogels, including the incorporation of conductive materials, fabrication techniques, and cross-linking interactions. We also discuss important characteristics for designing conductive hydrogels for directional growth and regenerative therapy. We propose insights into electrical conductivity properties in a hydrogel that could be implemented as guidance for directional cell growth for SCI applications. Specifically, we highlight the practical implications of recent findings in the field, including the potential for conductive hydrogels to be used in clinical applications. We conclude that conductive hydrogels are a promising neuroregenerative therapy for SCI and that further research is needed to optimize their design and application.

This article is part of the Biomaterials for Oral Medicine special issue. Oral delivery is considered the most painless, convenient, and widely acceptable route for drug administration due to patient compliance and ease of administration. (1,2) However, almost half of the currently available medications, and most biological molecules including proteins, peptides, antibodies, enzymes, and hormonal drugs, are not effective when administered via the oral route. (3) Large molecular drug molecules are not readily bioavailable in an oral dosage form as they are not stable in a harsh and acidic stomach environment and/or the molecules are too large to diffuse through the intestinal barrier (Figure 1). In addition, acidic gastric fluids, intestinal tight junctions, and a thick mucus layer can prevent absorption of orally administered drug molecules. (4) Figure 1. Large molecules or biological drugs have limited oral bioavailability because of acidic degradation in the stomach, enzymatic degradation in the small intestine, and poor permeability across the intestinal tight junction barrier. The image was prepared in www.biorender.com. This special issue aims to showcase articles focused on advanced technology such as 3D printing of oral formulations, and materials that can overcome gastrointestinal (GI) barriers, for instance, the acidic stomach, mucus, and intestinal tight junctions. In this special issue, we present one review and 10 research articles that discuss the prospects, potential, and feasibility of various materials and their role in the oral delivery of small and large molecular therapeutic modalities. Since the FDA approval of the first 3D printed tablet in 2015, 3D printing technology for pharmaceutical dosage forms including tablets and capsules has received significant attention by the formulation science community and pharmaceutical industries. (5) Here the article by Zhang et al describes 3D printing of oral tablets where the authors utilize magnetic nanoparticles as an alternative sintering agent. Selective laser sintering is a single-step process that has been gaining momentum in the 3D printing and manufacturing of pharmaceutical dosage forms. A carbonyl iron based multifunctional magnetic nanoparticle not only facilitates single-step 3D printed tablet production with lower laser energy but enhances as much as 25% more drug release under a magnetic field. This magnetic particle based oral tablet has shown potential for magnetic field-based controlled drug delivery and can be regulated externally upon magnetic field application. Furthermore, Reiländer et al. have reported on the development of a 3D printed oral dosage form for efficient delivery of carbon monoxide (CO) to treat intestinal bowel disease. This oral CO releasing system allows for a controlled release profile of CO from the device but prevents the release of other components including the molybdenum complex that was used to make the oral device. They have investigated the efficacy and biocompatibility using a porcine in vivo model and found it to be a very effective in oral delivery of CO. Over the last few decades, nanoparticle-based approaches have emerged for the oral delivery of small and large molecules. Here, Mathews et al. shows the development of chitosan- and alginate-based nanoparticles that can penetrate the intestinal barrier. The authors have investigated the efficacy of nanoparticles loaded with praziquantel, an anthelmintic drug, in a Corydoras schwartzi fish model and found these nanoparticles are effective in reducing intestinal parasites by 90% in the fish. The mucosal layer in the gastrointestinal tract plays a vital role in protecting the underlying tissues from the acidic gastric juice as well as maintaining gut homeostasis and health. However, mucus barriers are also one of the most significant barriers for oral drug absorption and transport, especially for large molecule drugs. In their review article, Wright et al. summarize various mucus barrier models that have been used to study in vitro drug transport and permeation of orally administered drugs. Such in vitro mucosal models could be very helpful in screening potential oral delivery carrier candidates and better understanding their permeability and diffusion profiles, and can potentially save time and resources prior to starting in vivo or preclinical studies. Along the same line, Jia et al. have reported on the utilization of an ex vivo model that can be used for understanding intestinal absorption and transcytosis of an orally administered nanoparticle. The authors have developed an optical clearing-based whole tissue imaging strategy to enable high resolution microscopic imaging of intestinal specimens that facilitate distribution of the nanoparticles within the intestinal villi and a quantitative analysis at the cellular level. In this study, the authors develop a polyethylene glycol-modified polystyrene nanoparticle, and show that introduction of Concanavalin A increases intestinal epithelium uptake of the particle by 4 times for nanoparticles with 200 nm in diameter, and ∼3 times for the nanoparticles with 50 nm in diameter. This ex vivo model can be used for understanding the intestinal transport profile of nanoparticles with different sizes in order to optimize nanoparticle-based carriers. Despite growing demand, oral protein delivery is very challenging due to the risk of degradation by the acidic environment in the stomach or enzymatic degradation in the small intestine. To address this issue, Lykins et al. has developed and investigated the effect of particle geometry and size on GT tract retention and distribution of orally administered particles. They observed that a planar and larger microdevice (>300 μm) has longer retention in the stomach than do smaller particles (<200 μm and less) in vivo. They also demonstrated that larger particles distribute across the GI tract but excrete more slowly. Interestingly, as the planar shaped microparticles translocate independently, the microdevices likely come in contact with the target site multiple times and these unique properties likely facilitate better therapeutic outcomes for GI tract specific local diseases. While protein oral delivery is a challenging area within the oral drug delivery field, Banun et al. has used milk-derived proteins for oral delivery of coenzyme-Q10, a hydrophobic small molecule that has antioxidant and anti-inflammatory effects. However, due to poor oral bioavailability, a higher dose of administration is required. The investigators encapsulated coenzyme-Q10 into the milk derived protein ß-lactoglubulin and lactoferrin and investigated their oral delivery using in vitro and in silico models. This protein-based nanoparticle was found to improve oral bioavailability of the payload and thereby improve therapeutic outcomes with a lower dose. In vitro caco-2 assays show a 2.5-fold higher permeability for the protein-based nanoparticle compared to that of free coenzyme-Q10. Moreover, these findings reveal that these milk-derived proteins could potentially be used to facilitate oral delivery of a wide range of hydrophobic small molecules. In the next article, Parvez et al. reported on the oral codelivery of biological and chemotherapeutic agents mediated by a solid lipid nanoparticle. The nanoparticle was grafted with 2-hydroporpyl-ß-cyclodextrin and loaded with melatonin and amphotericin B, and then evaluated for visceral lesihmaniasis treatment upon oral administration. The formulations were administered to L. donovani-infected BALB/c mice and the investigators observed more than a 95% reduction of intracellular parasites in liver tissue. No significant signs of toxicity were observed in macrophage culture and mouse models, showing promise as an effective oral drug delivery vehicle. Over the years, nanoemulsion-based delivery systems have also been attractive for the oral delivery of hydrophobic molecules. In their research article, Thanki et al. incorporated an oleyl acid-based emulsion for the oral delivery of amphotericin B to treat leishmaniasis and fungal infections. The authors have used both in vitro caco-2 cell monolayer and animal models to evaluate their approach and investigate the feasibility of the self-nanoemulsifying agent. Pharmacokinetics studies of this nanoemulsion, loaded with amphotericin B, show an almost 9-fold increase in oral bioavailability than that of free drug in Sprague–Dawley rats. More importantly, oral administration of this antibiotic shows significantly less systemic toxicity compared to intravenously administered free amphotericin B, supporting the biosafety and biocompatibility of this nanoemulsion based vehicle for oral delivery of antibiotics. In the next article of this issue, Vargason et al. report an advanced approach for oral delivery of live biotherapeutic agents. Carriers plat a very important role in live biotherapeutic delivery because carriers not only facilitate efficient delivery but can also maintain the viability and bioactivity of the loaded biotherapeutics. Moreover, unlike chemical-based therapeutics, intestinal retention for a certain duration of the orally administered biotherapeutic is necessary to achieve efficacy. To achieve this goal, the authors modified the surface of a live biotherapeutic payload through covalent and noncovalent chemistry. This surface modification is sought to control the interaction between the GI tract and the biotherapeutics, improve viability, increase attachment to the gut wall, and enhance therapeutic efficacy. The investigators evaluated the impact of surface modification on the growth of the biotherapeutic as well as loss of attachment over the time. This biocompatible surface modification chemistry can be utilized for cell and biotherapeutic delivery sciences. This special issue concludes with a research article on ionic liquid-based mucoadhesive patches for oral drug delivery reported by Mitragotri and colleagues. Ionic liquids have emerged as a promising approach in the noninvasive drug delivery field including oral delivery of biological therapeutics such as peptides and antibodies. (6) In this article the authors have developed a orally administered mucoadhesive patch for local and sustained release of a payload that has the potential to improve treatment of both local and systemic diseases. Previously, Mitragotri and his collaborators have developed choline bicarbonate and geranic acid (CAGE) based ionic liquids for the oral systemic delivery of insulin and found this approach to be effective in reducing blood glucose level in diabetes rats. (7) In this study, they extend these findings, developing a CAGE-patch in association with poly(vinyl alcohol) for sustained and controlled release of insulin upon oral administration. To show concept feasibility, insulin was loaded into the CAGE-patch and release profiles were determined using a Caco-2 and HT-29-MTX-E12 cell monolayer-based in vitro model. The patch showed 30% higher release of the insulin payload compared to the free insulin. Based on the findings in this report, this patch offers a new approach for oral controlled release of large molecules. With the increase in demand for oral medication and the growing number of biological therapeutics, the need for oral drug delivery technologies are more extensive than before. In this special issue we have compiled articles that discuss several biomaterials, techniques, and strategies for improving oral delivery of pharmacotherapeutics. Taken together, we believe that with continued investigation and efforts by the delivery scientists’ community, many of the intravenously administered therapeutics can be translated to oral dosage form for ease and painless administration (Figure 2). Figure 2. Biomaterials-based formulations in the form of nano/microparticles, emulsions, and liposomes can facilitate oral administration by protecting proteins, peptides, antibodies, and RNA from the harsh gastric/intestinal microenvironment and thereby enhance their intestinal retention, permeability, and bioavailability. The image was prepared in www.biorender.com. M.N. prepared the draft of the manuscript. T.A.D. edited, revised, and provided feedback on the manuscript. This article references 7 other publications. This article has not yet been cited by other publications. Figure 1. Large molecules or biological drugs have limited oral bioavailability because of acidic degradation in the stomach, enzymatic degradation in the small intestine, and poor permeability across the intestinal tight junction barrier. The image was prepared in www.biorender.com. Figure 2. Biomaterials-based formulations in the form of nano/microparticles, emulsions, and liposomes can facilitate oral administration by protecting proteins, peptides, antibodies, and RNA from the harsh gastric/intestinal microenvironment and thereby enhance their intestinal retention, permeability, and bioavailability. The image was prepared in www.biorender.com. This article references 7 other publications.

There is an evident advantage in personalized customization of orthopedic implants by 3D-printed titanium (Ti) and its alloys. However, 3D-printed Ti alloys have a rough surface structure caused by adhesion powders and a relatively bioinert surface. Therefore, surface modification techniques are needed to improve the biocompatibility of 3D-printed Ti alloy implants. In the present study, porous Ti6Al4V scaffolds were manufactured by a selective laser melting 3D printer, followed by sandblasting and acid-etching treatment and atomic layer deposition (ALD) of tantalum oxide films. SEM morphology and surface roughness tests confirmed that the unmelted powders adhered on the scaffolds were removed by sandblasting and acid-etching. Accordingly, the porosity of the scaffold increased by about 7%. Benefiting from the self-limitation and three-dimensional conformance of ALD, uniform tantalum oxide films were formed on the inner and outer surfaces of the scaffolds. Zeta potential decreased by 19.5 mV after depositing tantalum oxide films. The in vitro results showed that the adhesion, proliferation, and osteogenic differentiation of rat bone marrow mesenchymal stem cells on modified Ti6Al4V scaffolds were significantly enhanced, which may be ascribed to surface structure optimization and the compatibility of tantalum oxide. This study provides a strategy to improve the cytocompatibility and osteogenic differentiation of porous Ti6Al4V scaffolds for orthopedic implants.

Efficient local delivery of mesenchymal stem cells (MSCs) is a decisive factor for their application in regeneration processes. Here, we prepared a biomimetic bilayer silk fibroin/sodium alginate (SF/SA) scaffold to deliver human umbilical mesenchymal stem cells (hUC-MSCs) for wound healing. An SA membrane was prepared by the casting method on the upper layer of the scaffold to simulate the dense epidermal structure. On the lower layer, porous materials simulating the loose structure of the dermis were formed by the freeze-drying method. In vitro, the scaffold was proven to have a high-density pore structure, good swelling property, and suitable degradation rate. The hUC-MSCs could survive on the scaffold for up to 14 days and maintain cell stemness for at least 7 days. In vivo, SF/SA scaffolds loaded with hUC-MSCs (M-SF/SA) were applied to full-thickness defect wounds and compared with the local injection of hUC-MSCs. The M-SF/SA group showed excellent therapeutic efficacy, characterized by induction of macrophage polarization, regulation of TGF-β expression and collagen components, and enhancement of vascular regeneration, thereby preventing scar formation and promoting hair follicle regeneration. Furthermore, the expression of endoplasmic reticulum stress markers IRE1, XBP1, and CHOP was inhibited significantly in M-SF/SA treatment. In conclusion, the bilayer SF/SA scaffold is an ideal delivery platform for hUC-MSCs, and the M-SF/SA system could locally promote scarless skin healing and hair follicle regeneration by alleviating the IRE1/XBP1 signal pathway.

High Mobility Group Box 1 (HMGB1) is a redox-sensitive molecule that plays dual roles in tissue healing and inflammation. We previously demonstrated that HMGB1 is stable when anchored by a well-characterized imidazolium-based ionic liquid (IonL), which serves as a delivery vehicle for exogenous HMGB1 to the site of injury and prevents denaturation from surface adherence. However, HMGB1 exists in different isoforms [fully reduced HMGB1 (FR), a recombinant version of FR resistant to oxidation (3S), disulfide HMGB1 (DS), and inactive sulfonyl HMGB1(SO)] that have distinct biological functions in health and disease. Thus, the goal of this study was to evaluate the effects of different recombinant HMGB1 isoforms on the host response using a rat subcutaneous implantation model. A total of 12 male Lewis rats (12–15 weeks) were implanted with titanium discs containing different treatments (n = 3/time point; Ti, Ti-IonL, Ti-IonL-DS, Ti-IonL-FR, and Ti-IonL-3S) and assessed at 2 and 14 days. Histological (H&E and Goldner trichrome staining), immunohistochemistry, and molecular analyses (qPCR) of surrounding implant tissues were employed for analysis of inflammatory cells, HMGB1 receptors, and healing markers. Ti-IonL-DS samples resulted in the thickest capsule formation, increased pro-inflammatory, and decreased anti-inflammatory cells, while Ti-IonL-3S samples demonstrated suitable tissue healing similar to uncoated Ti discs, as well as an upregulation of anti-inflammatory cells at 14 days compared to all other treatments. Thus, results from this study demonstrated that Ti-IonL-3S are safe alternatives for Ti biomaterials. Future studies are necessary to investigate the healing potential of Ti-IonL-3S in osseointegration scenarios.

Despite numerous studies on tissue-engineered injectable cartilage, it is still difficult to realize stable cartilage formation in preclinical large animal models because of suboptimal biocompatibility, which hinders further application in clinical settings. In this study, we proposed a novel concept of cartilage regeneration units (CRUs) based on hydrogel microcarriers for injectable cartilage regeneration in goats. To achieve this goal, hyaluronic acid (HA) was chosen as the microparticle to integrate gelatin (GT) chemical modification and a freeze-drying technology to create biocompatible and biodegradable HA-GT microcarriers with suitable mechanical strength, uniform particle size, a high swelling ratio, and cell adhesive ability. CRUs were then prepared by seeding goat autologous chondrocytes on the HA-GT microcarriers and culturing in vitro. Compared with traditional injectable cartilage methods, the proposed method forms relatively mature cartilage microtissue in vitro and improves the utilization rate of the culture space to facilitate nutrient exchange, which is necessary for mature and stable cartilage regeneration. Finally, these precultured CRUs were used to successfully regenerate mature cartilage in nude mice and in the nasal dorsum of autologous goats for cartilage filling. This study provides support for the future clinical application of injectable cartilage.

Fibrosis of implants remains a significant challenge in the use of biomedical devices and tissue engineering materials. Antifouling coatings, including synthetic zwitterionic coatings, have been developed to prevent fouling and cell adhesion to several implantable biomaterials. While many of these coatings need covalent attachment, a conceptually simpler approach is to use a spontaneous self-assembly event to anchor the coating to a surface. This could simplify material processing through highly specific molecular recognition. Herein, we investigate the ability to utilize directional supramolecular interactions to anchor an antifouling coating to a polymer surface containing a complementary supramolecular unit. A library of controlled copolymerization of ureidopyrimidinone methacrylate (UPyMA) and 2-methacryloyloxyethyl phosphorylcholine (MPC) was prepared and their UPy composition was assessed. The MPC-UPy copolymers were characterized by 1H NMR, Fourier transform infrared (FTIR), and gel permeation chromatography (GPC) and found to exhibit similar mol % of UPy as compared to feed ratios and low dispersities. The copolymers were then coated on an UPy elastomer and the surfaces were assessed for hydrophilicity, protein absorption, and cell adhesion. By challenging the coatings, we found that the antifouling properties of the MPC-UPy copolymers with more UPy mol % lasted longer than the MPC homopolymer or low UPy mol % copolymers. As a result, the bioantifouling nature could be tuned to exhibit spatio-temporal control, namely, the longevity of a coating increased with UPy composition. In addition, these coatings showed nontoxicity and biocompatibility, indicating their potential use in biomaterials as antifouling coatings. Surface modification employing supramolecular interactions provided an approach that merges the simplicity and scalability of nonspecific coating methodology with the specific anchoring capacity found when using conventional covalent grafting with longevity that could be engineered by the supramolecular composition itself.

In recent years, bioactive ceramic bone scaffolds have drawn remarkable attention as an alternative method for treating and repairing bone defects. Vat photopolymerization (VP) is a promising additive manufacturing (AM) technique that enables the efficient and accurate fabrication of bioactive ceramic bone scaffolds. This review systematically reviews the research progress of VP-printed bioactive ceramic bone scaffolds. First, a summary and comparison of commonly used bioactive ceramics and different VP techniques are provided. This is followed by a detailed introduction to the preparation of ceramic suspensions and optimization of printing and heat treatment processes. The mechanical strength and biological performance of the VP-printed bioactive ceramic scaffolds are then discussed. Finally, current challenges and future research directions in this field are highlighted.

Engineered liposomal nanoparticles have unique characteristics as cargo carriers in cancer care and therapeutics. Liposomal theranostics have shown significant progress in preclinical and clinical cancer models in the past few years. Liposomal hybrid systems have not only been approved by the FDA but have also reached the market level. Nanosized liposomes are clinically proven systems for delivering multiple therapeutic as well as imaging agents to the target sites in (i) cancer theranostics of solid tumors, (ii) image-guided therapeutics, and (iii) combination therapeutic applications. The choice of diagnostics and therapeutics can intervene in the theranostics property of the engineered system. However, integrating imaging and therapeutics probes within lipid self-assembly “liposome” may compromise their overall theranostics performance. On the other hand, liposomal systems suffer from their fragile nature, site-selective tumor targeting, specific biodistribution and premature leakage of loaded cargo molecules before reaching the target site. Various engineering approaches, viz., grafting, conjugation, encapsulations, etc., have been investigated to overcome the aforementioned issues. It has been studied that surface-engineered liposomes demonstrate better tumor selectivity and improved therapeutic activity and retention in cells/or solid tumors. It should be noted that several other parameters like reproducibility, stability, smooth circulation, toxicity of vital organs, patient compliance, etc. must be addressed before using liposomal theranostics agents in solid tumors or clinical models. Herein, we have reviewed the importance and challenges of liposomal medicines in targeted cancer theranostics with their preclinical and clinical progress and a translational overview.

The SARS-CoV-2 global pandemic has reinvigorated interest in the creation and widespread deployment of durable, cost-effective, and environmentally benign antipathogenic coatings for high-touch public surfaces. While the contact-kill capability and mechanism of metallic copper and its alloys are well established, the biocidal activity of the refractory oxide forms remains poorly understood. In this study, commercial cuprous oxide (Cu2O, cuprite) powder was rapidly nanostructured using high-energy cryomechanical processing. Coatings made from these processed powders demonstrated a passive “contact-kill” response to Escherichia coli (E. coli) bacteria that was 4× (400%) faster than coatings made from unprocessed powder. No viable bacteria (>99.999% (5-log10) reduction) were detected in bioassays performed after two hours of exposure of E. coli to coatings of processed cuprous oxide, while a greater than 99% bacterial reduction was achieved within 30 min of exposure. Further, these coatings were hydrophobic and no external energy input was required to activate their contact-kill capability. The upregulated antibacterial response of the processed powders is positively correlated with extensive induced crystallographic disorder and microstrain in the Cu2O lattice accompanied by color changes that are consistent with an increased semiconducting bandgap energy. It is deduced that cryomilling creates well-crystallized nanoscale regions enmeshed within the highly lattice-defective particle matrix. Increasing the relative proportion of lattice-defective cuprous oxide exposed to the environment at the coating surface is anticipated to further enhance the antipathogenic capability of this abundant, inexpensive, robust, and easily handled material for wider application in contact-kill surfaces.

Elucidating the fouling phenomena of polymer surfaces will facilitate the molecular design of high-performance biomedical devices. Here, we investigated the remarkable antifouling properties of two acrylate materials, poly(2-methoxyethyl acrylate) (PMEA) and poly(3-methoxypropionic acid vinyl ester) (PMePVE), which have a terminal methoxy group on the side chain, via molecular dynamics simulations of binary mixtures of acrylate/methacrylate trimers with n-pentane or 2,2-dimethylpropane (neopentane), that serve as the nonpolar organic probe (organic foulants). The second virial coefficient (B2) was determined to assess the aggregation/dispersion properties in the binary mixtures. The order of the B2 values for the trimer/pentane mixtures indicated that the terminal methoxy group of the side chain plays an important role in enhancing the fouling resistance to nonpolar organic foulants. Here, we hypothesized that the antifouling properties of PMEA/PMePVE surfaces originate from the resistance. To evaluate the molecular-level accessibility of organic foulants to acrylate/methacrylate materials, we examined the radial distribution functions (RDFs) of the terminal methyl groups of neopentane around the main chains of the acrylate/methacrylate trimers. As a result, the third distinct RDF peaks are observed only for the methacrylate trimers. The peaks are attributed to the hydrophobic interactions between the methyl group of neopentane and that of the main chain of the trimer. Accordingly, the methyl group of the main chain of methacrylate materials, such as poly(2-hydroxyethyl methacrylate) and poly(2-methoxyethyl methacrylate), unfavorably induces fouling with organic foulants. In this study, we clarify that preventing hydrophobic interactions between an organic foulant and polymeric material is essential for enhancing the antifouling property. Our approach has great potential for evaluating the molecular-level affinities of organic foulant with polymer surfaces for the molecular design of excellent antifouling polymeric materials.

The biocompatibility and biodegradation of iron (Fe) make it a suitable candidate for developing biodegradable metallic implants. However, the degradation rate of Fe in a physiological environment is extremely slow and needs to be enhanced to a rate compatible with tissue growth. Incorporating noble metals improves the Fe degradation rate by forming galvanic couples. This study incorporated gold (Au) into Fe at very low concentrations of 1.25 and 2.37 μg/g to improve the degradation rate. The electrochemical corrosion test of the samples revealed that the Au-containing samples showed a four-time and nine-time faster degradation rate than pure Fe. Furthermore, the immersion test and long-term electrochemical impedance spectroscopy conducted in simulated body fluid (SBF) revealed that the Au-incorporated samples exhibited increased bioactivity and degraded faster than pure Fe. Integrating nanogold into a Fe matrix increased the in situ formation of hydroxyapatite on the sample’s surface and did not cause toxicity to L929-murine fibroblast cells. It is suggested that Fe–Au composites with low concentrations of Au can be used to tailor the biodegradation rate and promote the biomineralization of Fe-based implants in the physiological environment.

Silicone and e-poly(tetrafluoroethylene) (e-PTFE) are the most commonly used artificial materials for repairing maxillofacial bone defects caused by facial trauma and tumors. However, their use is limited by poor histocompatibility, unsatisfactory support, and high infection rates. Polyetheretherketone (PEEK) has excellent mechanical strength and biocompatibility, but its application to the repair of maxillofacial bone defects lacks a theoretical basis. The microstructure and mechanical properties of e-PTFE, silicone, and PEEK were evaluated by electron microscopy, BOSE machine, and Fourier transformed infrared spectroscopy. Mouse fibroblast L929 cells were incubated on the surface of the three materials to assess cytotoxicity and adhesion. The three materials were implanted onto the left femoral surface of 90 male mice, and samples of the implants and surrounding soft tissues were evaluated histologically at 1, 2, 4, 8, and 12 weeks post-surgery. PEEK had a much higher Young’s modulus than either e-PTFE or silicone (p 0.05 each). Connective tissue ingrowth was observed in PEEK and e-PTFE, whereas a fibrotic peri-prosthetic capsule was observed on the surface of silicone. The postoperative infection rate was significantly lower for both PEEK and silicone than for e-PTFE (p < 0.05 each). PEEK shows excellent biocompatibility and mechanical stability, suggesting that it can be effective as a novel implant to repair maxillofacial bone defects.

Technological advancement in the field of dentistry has to be proven in new avenues for professionals as well as laboratory programmers. An advanced type of technology is emerging based on digitalization, as a computerized three-dimensional (3-D) model, additive manufacturing also called 3-D printing, allows formation of block pieces by adding material layer-by-layer. The additive manufacturing (AM) approach has offered extreme progress in the broad choice of distinct zones, permitting the production of fragments of all possible varieties of substances such as metal, polymer, ceramic, and composites. The significant goal of current the article is to recapitulate the recent scenarios including the imminent perspective of AM techniques and challenges in dentistry. Moreover, this article reviews the recent developments of 3-D printing advancements along with the advantages and disadvantages. Herein, various AM technologies comprising vat photopolymerization (VPP), material jetting, material extrusion, selective laser sintering (SLS), selective laser melting (SLM), and direct metal laser sintering (DMLS) technologies based powder bed fusion technologies/direct energy deposition/sheet lamination centered on binder jetting technologies were discussed in detail. This paper attempts to provide a balanced view by emphasizing the economic, scientific, and technical challenges and presenting an overview of methods to discuss the similarities based on the authors’ continuing research and development.

Drug loading of polymer micelles can have a profound effect on their particle size and morphology as well as their physicochemical properties. In turn, this influences performance in biological environments. For oral delivery of drugs, the intestinal environment is key, and consequently, a thorough structural understanding of what happens at this material–biology interface is required to understand in vivo performance and tailor improved delivery vehicles. In this study, we address this interface in vitro through a detailed structural characterization of the colloidal assemblies of polymeric micelles based on poly(2-oxazolines) with three different guest loadings with the natural product curcumin (17–52 wt %) in fed-state simulated intestinal fluids (FeSSIF). For this, we employ NMR spectroscopy, in particular, 1H NMR, 1H–1H-NOESY, and 1H DOSY experiments complemented by quantum chemical calculations and cryo-TEM measurements. Through this mixture of methods, we identified curcumin–taurocholate interactions as central interaction patterns alongside interactions with the polymer and lipids. Furthermore, curcumin molecules can be exchanged between polymer micelles and bile colloids, an important prerequisite for their uptake. Finally, increased loading of the polymer micelles with curcumin resulted in a larger number of vesicles as taurocholate─through coordination with Cur─is less available to form nanoparticles with the lipids. The loading-dependent behavior found in this study deviates from previous work on a different drug substance highlighting the need for further studies including different drug molecules and polymer types to improve the understanding of events on the molecular level.

This article is part of the Engineering Bioinspired and Biological Materials special issue. This article references 18 other publications. This article has not yet been cited by other publications. This article references 18 other publications.

Photoactivating dental resin composites have been the most prevailing material for repairing dental defects in various clinical scenarios due to their multiple advantages. However, compared to other restorative materials, the surface of resin-based composites is more susceptible to plaque biofilm accumulation, which can lead to secondary caries and restoration failure. This study introduced different weight fractions (1, 2, 5, 10, and 15%) of magnesium oxide nanoparticles (MgONPs) as antibacterial fillers into dental resin composites. Multifarious properties of the material were investigated, including antibacterial activity against a human salivary plaque-derived biofilm, cytotoxicity on human gingival fibroblasts, mechanical and physicochemical properties as well as the performance when subjected to thermocycling aging treatment. Results showed that the incorporation of MgONPs significantly improved the composites’ anti-biofilm capability even at a low amount of 2 wt % without compromising the mechanical, physicochemical, and biocompatibility performances. The results of the thermocycling test suggested certain of aging resistance. Moreover, a small amount of MgONPs possibly made a difference in enhancing photoactivated polymerization and increasing the curing depth of experimental resin composites. Overall, this study highlights the potential of MgONPs as an effective strategy for developing antibacterial resin composites, which may help mitigating cariogenic biofilm-associated secondary caries.