Tissue engineering approaches such as the electrospinning technique can fabricate nanofibrous scaffolds which are widely used for small-diameter vascular grafting. However, foreign body reaction (FBR) and lack of endothelial coverage are still the main cause of graft failure after the implantation of nanofibrous scaffolds. Macrophage-targeting therapeutic strategies have the potential to address these issues. Here, we fabricate a monocyte chemotactic protein-1 (MCP-1)-loaded coaxial fibrous film with poly(l-lactide-co-ε-caprolactone) (PLCL/MCP-1). The PLCL/MCP-1 fibrous film can polarize macrophages toward anti-inflammatory M2 macrophages through the sustained release of MCP-1. Meanwhile, these specific functional polarization macrophages can mitigate FBR and promote angiogenesis during the remodeling of implanted fibrous films. These studies indicate that MCP-1-loaded PLCL fibers have a higher potential to modulate macrophage polarity, which provides a new strategy for small-diameter vascular graft designing.

Streptococcus mutans is one of the key etiological factors in tooth-borne biofilm development that leads to dental caries in the presence of fermentable sugars. We previously reported on the ability of acid-stabilized nanoceria (CeO2-NP) produced by the hydrolysis of ceric salts to limit biofilm adherence of S. mutans via non-bactericidal mechanism(s). Herein, we report a chondroitin sulfate A (CSA) formulation (CeO2-NP-CSA) comprising nanoceria aggregates that promotes resistance to bulk precipitation under a range of conditions with retention of the biofilm-inhibiting activity, allowing for a more thorough mechanistic study of its bioactivity. The principal mechanism of reduced in vitro biofilm adherence of S. mutans by CeO2-NP-CSA is the production of nonadherent cell clusters. Additionally, dose-dependent in vitro human cell toxicity studies demonstrated no additional toxicity beyond that of equimolar doses of sodium fluoride, currently utilized in many oral health products. This study represents a unique approach and use of a nanoceria aggregate formulation with implications for promoting oral health and dental caries prevention as an adjunctive treatment.

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), and maintained high stiffness without degradation long after implantation. Both PEEK and e-PTFE facilitated L929 cell adhesion, with PEEK having lower cytotoxicity than e-PTFE and silicone (p < 0.05 each). All three materials similarly hindered the motor function of mice 12 weeks after implantation (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.

Hydrogels are considered to be ideal biomedical materials as their physical properties are similar to the physiological tissue environment. In particular, thixotropic hydrogels have received increasing attention from researchers because of their injectability. Herein, a simple and rapid method was developed for the preparation of a regenerated silk fibroin (RSF) hydrogel with long-lasting and excellent thixotropy. The thixotropic RSF hydrogel was readily formed by ultrasonic treatment of the pretreated RSF solution for 2 min followed by incubation at 40 °C for 10 min. The storage modulus of the RSF hydrogels recovered to more than 90% of the original value within 20 s after withstanding 1000% shear strain. By avoiding complicated chemical or physical treatments and by addition of crosslinking agents and/or other chemical components, the obtained RSF hydrogels maintained excellent biocompatibility. Hence, the cells implanted inside the hydrogel can grow and proliferate normally. By virtue of ultrasonic treatment during the preparation, functional nanoparticles can be uniformly dispersed in the RSF solution to prepare RSF-based hybrid hydrogels with various functions. As an application example, hydroxyapatite (HAP) with osteoinductivity was mixed with RSF solution to prepare the RSF/HAP hybrid hydrogel. The RSF/HAP hybrid hydrogel maintained biocompatibility and thixotropy of the original RSF hydrogel and promoted osteoblastic differentiation of cells owing to the addition of HAP. Therefore, the RSF hydrogel prepared in this work has a strong application prospect in the biomedical field including, but not limited to, bone repair.

Low efficiency of targeting and delivery toward the thrombus site poses challenges to using thrombolytic drugs. Inspired by the biomimetic system of platelet membranes (PMs) and glucose oxidase (GOx) modification technologies, we develop a novel GOx-powered Janus nanomotor by asymmetrically attaching the GOx to polymeric nanomotors coated with the PMs. Then the PM-coated nanomotors were conjugated with urokinase plasminogen activators (uPAs) on their surfaces. The PM-camouflaged design conferred excellent biocompatibility to the nanomotors and improved their targeting ability to thrombus. The Janus distribution of GOx also allows the uneven decomposition of glucose in biofluids to produce a chemophoretic motion, increasing the drug delivery efficiency of nanomotors. In addition, these nanomotors are located at the lesion site due to the mutual adhesion and aggregation of platelet membranes. Furthermore, thrombolysis effects of nanomotors are enhanced in static and dynamic thrombus as well as in mouse models. It is believed that the novel PM-coated enzyme-powered nanomotors represent a great value for thrombolysis treatment.

Adverse remodeling post-myocardial infarction is hallmarked by the phenotypic change of cardiac fibroblasts (CFs) into myofibroblasts (MyoFs) and over-deposition of the fibrotic extracellular matrix (ECM) mainly composed by fibronectin and collagens, with the loss of tissue anisotropy and tissue stiffening. Reversing cardiac fibrosis represents a key challenge in cardiac regenerative medicine. Reliable in vitro models of human cardiac fibrotic tissue could be useful for preclinical testing of new advanced therapies, addressing the limited predictivity of traditional 2D cell cultures and animal in vivo models. In this work, we engineered a biomimetic in vitro model, reproducing the morphological, mechanical, and chemical cues of native cardiac fibrotic tissue. Polycaprolactone (PCL)-based scaffolds with randomly oriented fibers were fabricated by solution electrospinning technique, showing homogeneous nanofibers with an average size of 131 ± 39 nm. PCL scaffolds were then surface-functionalized with human type I collagen (C1) and fibronectin (F) by dihydroxyphenylalanine (DOPA)-mediated mussel-inspired approach (PCL/polyDOPA/C1F), in order to mimic fibrotic cardiac tissue-like ECM composition and support human CF culture. BCA assay confirmed the successful deposition of the biomimetic coating and its stability during 5 days of incubation in phosphate-buffered saline. Immunostaining for C1 and F demonstrated their homogeneous distribution in the coating. AFM mechanical characterization showed that PCL/polyDOPA/C1F scaffolds, in wet conditions, resembled fibrotic tissue stiffness with an average Young’s modulus of about 50 kPa. PCL/polyDOPA/C1F membranes supported human CF (HCF) adhesion and proliferation. Immunostaining for α-SMA and quantification of α-SMA-positive cells showed HCF activation into MyoFs in the absence of a transforming growth factor β (TGF-β) profibrotic stimulus, suggesting the intrinsic ability of biomimetic PCL/polyDOPA/C1F scaffolds to sustain the development of cardiac fibrotic tissue. A proof-of-concept study making use of a commercially available antifibrotic drug confirmed the potentialities of the developed in vitro model for drug efficacy testing. In conclusion, the proposed model was able to replicate the main hallmarks of early-stage cardiac fibrosis, appearing as a promising tool for future preclinical testing of advanced regenerative therapies.

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.

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.

In bone tissue engineering, the performance of scaffolds underpins the success of the healing of bone. Microbial infection is the most challenging issue for orthopedists. The application of scaffolds for healing bone defects is prone to microbial infection. To address this challenge, scaffolds with a desirable shape and significant mechanical, physical, and biological characteristics are crucial. 3D printing of antibacterial scaffolds with suitable mechanical strength and excellent biocompatibility is an appealing strategy to surmount issues of microbial infection. The spectacular progress in developing antimicrobial scaffolds, along with beneficial mechanical and biological properties, has sparked further research for possible clinical applications. Herein, the significance of antibacterial scaffolds designed by 3D, 4D, and 5D printing technologies for bone tissue engineering is critically investigated. Materials such as antibiotics, polymers, peptides, graphene, metals/ceramics/glass, and antibacterial coatings are used to impart the antimicrobial features for the 3D scaffolds. Polymeric or metallic biodegradable and antibacterial 3D-printed scaffolds in orthopedics disclose exceptional mechanical and degradation behavior, biocompatibility, osteogenesis, and long-term antibacterial efficiency. The commercialization aspect of antibacterial 3D-printed scaffolds and technical challenges are also discussed briefly. Finally, the discussion on the unmet demands and prevailing challenges for ideal scaffold materials for fighting against bone infections is included along with a highlight of emerging strategies in this field.

Helical amphipathic peptides containing cationic and hydrophobic amino acid residues can possess potent antimicrobial activity against both Gram-positive and Gram-negative bacteria. In this study, several amphipathic peptides with enhanced helical structures containing nonproteinogenic amino acids were designed, and the relationships between the antimicrobial activity, hemolytic activity, and cytotoxicity were evaluated. In particular, the effect on the antimicrobial activity and cytotoxicity of the number and position of stapling structures introduced into the sequence was investigated. Peptide stp1 containing α,α-disubstituted amino acids showed potent antimicrobial activity against multidrug-resistant bacteria (MDRP, SP45, and Staphylococcus aureus) without causing appreciable hemolytic activity or cytotoxicity. The cytotoxicity was found to be somewhat correlated to the hydrophobicity of the peptides.

The manufacturing process of chimeric antigen receptor T cell therapies includes isolation systems that provide pure T cells. Current magnetic-activated cell sorting and immunoaffinity chromatography methods produce desired cells with high purity and yield but require expensive equipment and reagents and involve time-consuming incubation steps. Here, we demonstrate that aptamers can be employed in a continuous-flow resin platform for both depletion of monocytes and selection of CD8+ T cells from peripheral blood mononuclear cells at low cost with high purity and throughput. Aptamer-mediated cell selection could potentially enable fully synthetic, traceless isolations of leukocyte subsets from a single isolation system.

Polymeric microparticles are promising biomaterial platforms for targeting macrophages in the treatment of disease. This study investigates microparticles formed by a thiol-Michael addition step-growth polymerization reaction with tunable physiochemical properties and their uptake by macrophages. The hexafunctional thiol monomer dipentaerythritol hexa-3-mercaptopropionate (DPHMP) and tetrafunctional acrylate monomer di(trimethylolpropane) tetraacrylate (DTPTA) were reacted in a stepwise dispersion polymerization, achieving tunable monodisperse particles over a size range (1–10 μm) relevant for targeting macrophages. An off-stoichiometry thiol-acrylate reaction afforded facile secondary chemical functionalization to create particles with different chemical moieties. Uptake of the microparticles by RAW 264.7 macrophages was highly dependent on treatment time, particle size, and particle chemistry with amide, carboxyl, and thiol terminal chemistries. The amide-terminated particles were non-inflammatory, while the carboxyl- and thiol-terminated particles induced pro-inflammatory cytokine production in conjunction with particle phagocytosis. Finally, a lung-specific application was explored through time-dependent uptake of amide-terminated particles by human alveolar macrophages in vitro and mouse lungs in vivo without inducing inflammation. The findings demonstrate a promising microparticulate delivery vehicle that is cyto-compatible, is non-inflammatory, and exhibits high rates of uptake by macrophages.

Titanium alloy porous scaffolds possess excellent mechanical properties and biocompatibility, making them promising for applications in bone tissue engineering. The integration of triply periodic minimal surface (TPMS) with porous scaffolds provides a structural resemblance to the trabecular and cortical bone structures of natural bone tissue, effectively reducing stress-shielding effects, enabling the scaffold to withstand complex stress environments, and facilitating nutrient transport. In this study, we designed fused porous scaffolds based on the Gyroid and Diamond units within TPMS and fabricated samples using selective laser melting technology. The effects of the rotation direction and angle of the inner-layer G unit on the elastic modulus of the fused TPMS porous scaffold were investigated through quasi-static compression experiments. Furthermore, the influence of the rotation direction and angle of the inner-layer G unit on the permeability, pressure, and flow velocity of the fused TPMS porous scaffold structure was studied using computational fluid dynamics (CFD) based on the Navier–Stokes model. The quasi-static compression experiment results demonstrated that the yield strength of the fused TPMS porous scaffold ranged from 367.741 to 419.354 MPa, and the elastic modulus ranged from 10.617 to 11.252 GPa, exhibiting stable mechanical performance in different loading directions. The CFD simulation results indicated that the permeability of the fused TPMS porous scaffold model ranged from 5.70015 × 10–8 to 6.33725 × 10–8 m2. It can be observed that the fused porous scaffold meets the requirements of the complex stress-bearing demands of skeletal structures and complies with the permeability requirements of human bone tissue.

While millions of ureteral stents are placed in patients with urinary tract issues around the world every year, hydronephrosis still poses great danger to these patients as a common complication. In the present work, an intelligent double-J ureteral stent equipped with a micro pressure sensor and antenna circuitry is investigated and prototyped toward enabling continuous wireless monitoring of kidney pressure to detect a ureteral obstruction and the resultant hydronephrosis via the indwelling stent. This electromechanically functionalized “intelligent” ureteral stent acts as a radiofrequency resonator with a pressure-sensitive resonant frequency that can be interrogated using an external antenna to track the local pressure. The prototype passes mechanical bending tests of up to 15 cm radius of curvature and shows wireless sensing with a sensitivity of 3.1 kHz/mmHg in artificial urine, which represents 25× enhancement over the preceding design, using an in vitro model with test tissue layers and a pressure range that functions within the conditions found in hydronephrotic conditions. These promising results are expected to propel intelligent ureteral stent technology into further clinical research.

A novel method for hydroxyapatite fiber preparation with highly large-scale production prospects is of paramount importance but remains particularly difficult. Here, group replacement–rearrangement-triggered linear-assembly nonaqueous precipitation synthesis has been proposed for hydroxyapatite fibers under mild conditions. Pure hydroxyapatite fibers can be fabricated taking disodium hydrogen phosphate, calcium acetate, and glycerol as the phosphorus source, calcium source, and solvent, respectively. Single hexagonal crystal structures of hydroxyapatite fibers growing along the c-axis and preferential growth of the (002) crystal plane similar to the layered stacking structure of an adult bone have been confirmed by XRD refinement tests and calculation, TEM electron diffraction calibration, and FE-SEM. Highly active carbonate apatite is further demonstrated by EDS, FT-IR, Raman spectroscopy, and XPS. Unsaturated P–O and O–Ca bonds at both ends of the hexagonal-sheet assembly unit in a high-polarity nonaqueous glycerol environment without strongly coordinated OH– confirm the solution spontaneous linear assembly to form the single hydroxyapatite fibers.

Triboelectric nanogenerators (TENGs) are associated with several drawbacks that limit their application in the biomedical field, including toxicity, thrombogenicity, and poor performance in the presence of fluids. By proposing the use of a hemo/biocompatible hydrogel, poly(2-hydroxyethyl methacrylate) (pHEMA), this study bypasses these barriers. In contact–separation mode, using polytetrafluoroethylene (PTFE) as a reference, pHEMA generates an output of 100.0 V, under an open circuit, 4.7 μA, and 0.68 W/m2 for an internal resistance of 10 MΩ. Our findings unveil that graphene oxide (GO) can be used to tune pHEMA’s triboelectric properties in a concentration-dependent manner. At the lowest measured concentration (0.2% GO), the generated outputs increase to 194.5 V, 5.3 μA, and 1.28 W/m2 due to the observed increase in pHEMA’s surface roughness, which expands the contact area. Triboelectric performance starts to decrease as GO concentration increases, plateauing at 11% volumetric, where the output is 51 V, 1.76 μA, and 0.17 W/m2 less than pHEMA’s. Increases in internal resistance, from 14 ΩM to greater than 470 ΩM, ζ-potential, from −7.3 to −0.4 mV, and open-circuit characteristic charge decay periods, from 90 to 120 ms, are all observed in conjunction with this phenomenon, which points to GO function as an electron trapping site in pHEMA’s matrix. All of the composites can charge a 10 μF capacitor in 200 s, producing a voltage between 0.25 and 3.5 V and allowing the operation of at least 20 LEDs. The triboelectric output was largely steady throughout the 3.33 h durability test. Voltage decreases by 38% due to contact–separation frequency, whereas current increases by 77%. In terms of pressure, it appears to have little effect on voltage but boosts current output by 42%. Finally, pHEMA and pHEMA/GO extracts were cytocompatible toward fibroblasts. According to these results, pHEMA has a significant potential to function as a biomaterial to create bio/hemocompatible TENGs and GO to precisely control its triboelectric outputs.

Polyethylene glycol (PEG) was utilized to functionalize the surface of zinc ferrite nanoparticles (NPs) synthesized by the hydrothermal process in order to prevent aggregation and improve the biocompatibility of the NPs for the proposed magnetic resonance imaging (MRI) agent. Various spectroscopy techniques were used to examine the NPs’ structure, size, morphology, and magnetic properties. The NPs had a cubic spinel structure with an average size of 8 nm. The formations of the spinel ferrite and the PEG coating band at the ranges of 300–600 and 800–2000 cm–1, respectively, were validated by Fourier-transform infrared spectroscopy. The NPs were spherical in shape, and energy-dispersive X-ray spectroscopy with mapping confirmed the presence of zinc, iron, and oxygen in the samples. The results of high-resolution transmission electron microscopy revealed an average size of 14 nm and increased stability after PEG coating. The decrease in zeta potential from −24.5 to −36.5 mV confirmed the PEG coating on the surface of the NPs. A high saturation magnetization of ∼50 emu/g, measured by vibration sample magnetometer, indicated the magnetic potential of NPs for biomedical applications. An MTT assay was used to examine the cytotoxicity and viability of human normal skin cells (HSF 1184) exposed to zinc ferrite and PEG@Zn ferrite NPs at various concentrations. After 24 h of treatment, negligible cytotoxicity of PEG-coated NPs was observed at high concentrations. Magnetic resonance imaging (MRI) suggested that PEG@Zn ferrite NPs are a unique and perfectly suited contrast agent for T2-weighted MRI and can successfully enhance the image contrast.

Vascular endothelial growth factor A-165 (VEGF-A165) positively modulates neointimal hyperplasia, lumen stenosis, and neovascularization. One challenge for the use of VEGF-A165 for potential therapy is its short serum half-life. Therefore, we are designing VEGF-A165 bioconjugates carrying polyethylene glycol (PEG). The purity of the recombinantly expressed human VEGF-A165 exceeded 90%. The growth factor had a half-maximal effective concentration of 0.9 ng/mL (EC50) and induced tube formation of human umbilical vein endothelial cells. PEGylation was conducted by Schiff base reaction followed by reductive amination. After purification, two species were obtained, with one or two PEG attached per VEGF-A165 dimer. Both resulting bioconjugates had a purity exceeding 90%, wild-type bioactivity, and increased hydrodynamic radii as required for prolonging the half-life.

Since the physical properties are similar to native extracellular matrices, double network (DN) hydrogels have been studied extensively in the tissue engineering. However, the double chemical crosslinked DN hydrogel is limited by poor fatigue resistance. π–π stacking is a non-covalent bonding interaction, which is essential to maintain and self-assemble the three-dimensional structure of biological proteins and nucleic acids. In this study, a robust polyethylene glycol diacrylate (PEGDA)/FFK hybrid DN hydrogel was prepared by Michael addition and π–π stacking. The hybrid DN hydrogels with π–π stacking interactions have excellent mechanical strength and fatigue resistance. The DN FFK/PEGDA hydrogels reveal great biocompatibility and hemocompatibility. The DN hydrogels containing π–π stacking have the potential to fabricate robust hybrid DN hydrogels in drug release and tissue engineering.

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.