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Dental decay is treated by removing infected dental tissues such as dentine and restoring the tooth with a material. However, the vast majority of these materials have been designed to be mechanically robust and bioinert, whereas the potential regenerative properties of a biomaterial have not been considered. In endodontics for example, materials are used to seal the pulp cavity to avoid bacterial colonisation of the tooth and prevent further infection. While these treatments are effective in the short term, many of these materials have not been designed to interface with the pulp tissue in a biocompatible manner and are often cytotoxic. This can lead to less favourable long-term outcomes such as devitalisation of the tooth via root-canal therapy or extraction of the tooth. Clinical outcomes could be improved if regenerative approaches were followed whereby the biology of the tooth is engineered for repair and regeneration often with the support of a biomaterial. Within these, acellular or cell homing approaches are particularly interesting, as some regulatory hurdles associated with cellular therapies could be circumvented which may aid their clinical translation. In this review, we highlight progress in regenerative dentistry and focus on exciting developments using acellular biomaterials for regenerating dental tissues.

This study was developed based on in vivo investigation of microporous granular biomaterials based on calcium phosphates, involving matrices of β-tricalcium phosphate (β-TCP), hydroxyapatite (HA), biphasic compositions of both phases and a control group. The physicochemical characterization of materials was carried out by X-Ray diffraction (DRX) and mercury porosimetry. Biodegradability, bioactivity and neoformation processes were investigated by Raman spectroscopy, scanning electron microscopy (SEM) and polarized light conducted on biopsies obtained from in vivo tests for periods of 90 and 180 days. These were performed to evaluate the behavior of granular microporous compositions in relation to bone neoformation. Through the performance obtained from in vivo assays, excellent osseointegration and bone tissue neoformation were observed. The results are encouraging and show that the microporous granular biomaterials of HA, β-TCP and biphasic compositions show similar results with perfect osseointegration. Architectures simulating a bone structure can make the difference between biomaterials for bone tissue replacement and repair.

The use of injectable materials as a biofiller for soft tissue augmentation has been increasing worldwide. Levan is a biocompatible and inexpensive polysaccharide with great potential in biomaterial applications, but it has not been extensively studied. In this study, we evaluated the potential of levan as a new material for dermal fillers and prepared an injectable and physical levan-based hydrogel by combining levan with Pluronic and carboxymethyl cellulose (CMC). A sol state was prepared by mixing the polymers in a specific ratio at 4 °C for 2 days and the hydrogel was formed by increasing the temperature to 37 °C. The elastic modulus of the levan hydrogel was higher than that of a hyaluronic acid (HA)-based hydrogel. The SEM images of the levan hydrogel showed an interconnected porous structure, similar to the HA hydrogel. Levan showed non-cytotoxicity, enhanced cell proliferation, and higher amount of collagen synthesis in human dermal fibroblast cells compared to HA. The injected levan hydrogel was biocompatible and stable over 2 weeks in vivo , longer than the Pluronic F127 hydrogel or HA hydrogel. Also, the levan hydrogel showed a higher amount of collagen production than the HA hydrogel in vivo . More importantly, the levan hydrogel showed enhanced anti-wrinkle efficacy compared to the HA hydrogel in a wrinkle model mouse. Thus, the levan hydrogel with injectability, biocompatibility, and an anti-wrinkle effect has high potential as an alternative to existing commercial dermal fillers.

Currently, the treatment and care of diabetic wounds, which generally possess the characteristics of a high amputation rate, high recurrence rate and high mortality, has developed into a worldwide challenge. Wound dressings have been playing an important role in diabetic wound treatment and continuously innovated to obtain many amazing properties. Among them, hydrogel dressings have become one of the most attractive and promising wound dressings because of their considerable moisture retention, biocompatibility and therapeutic properties. In recent years, with the in depth understanding of the pathogenesis of diabetic wounds, various functionalized hydrogel dressings have been reported and shown encouraging results, which has brought great benefits to the improvement of diabetic wounds. In this work, we will systematically and comprehensively summarize the advances of hydrogel dressings in diabetic wounds, aiming to provide not only theoretical support for hydrogel dressing devising but also inspiration for diabetic wound treatment.

Topological design provides additively manufactured (AM) biodegradable porous metallic biomaterials with a unique opportunity to adjust their biodegradation behavior and mechanical properties, thereby satisfying the requirements for ideal bone substitutes. However, no information is available yet concerning the effect of topological design on the performance of AM porous zinc (Zn) that outperforms Mg and Fe in biodegradation behavior. Here, we studied one functionally graded and two uniform AM porous Zn designs with diamond unit cell. Cylindrical specimens were fabricated from pure Zn powder by using a powder bed fusion technique, followed by a comprehensive study on their static and dynamic biodegradation behaviors, mechanical properties, permeability, and biocompatibility. Topological design, indeed, affected the biodegradation behavior of the specimens, as evidenced by 150% variations in biodegradation rate between the three different designs. After in vitro dynamic immersion for 28 days, the AM porous Zn had weight losses of 7–12%, relying on the topological design. The degradation rates satisfied the desired biodegradation time of 1–2 years for bone substitution. The mechanical properties of the biodegraded specimens of all the groups maintained within the range of those of cancellous bone. As opposed to the trends observed for other biodegradable porous metals, after 28 days of in vitro biodegradation, the yield strengths of the specimens of all the groups ( σ y = 7–14 MPa) increased consistently, as compared to those of the as-built specimens ( σ y = 4–11 MPa). Moreover, AM porous Zn showed excellent biocompatibility, given that the cellular activities in none of the groups differed from the Ti controls for up to 72 h. Using topological design of AM porous Zn for controlling its mechanical properties and degradation behavior is thus clearly promising, thereby rendering flexibility to the material to meet a variety of clinical requirements.

Although polymeric nanoconjugates (NCs) hold great promise for the treatment of cancer patients, their clinical utility has been hindered by the lack of efficient delivery of therapeutics to targeted tumor sites. Here, we describe an albumin-functionalized polymeric NC (Alb-NC) capable of crossing the endothelium barrier through a caveolae-mediated transcytosis pathway to better target cancer. The Alb-NC is prepared by nanoprecipitation of doxorubicin (Doxo) conjugates of poly(phenyl O -carboxyanhydrides) bearing aromatic albumin-binding domains followed by subsequent surface decoration of albumin. The administration of Alb-NCs into mice bearing MCF-7 human breast cancer xenografts with limited tumor vascular permeability resulted in markedly increased tumor accumulation and anti-tumor efficacy compared to their conventional counterpart PEGylated NCs (PEG-NCs). The Alb-NC provides a simple, low-cost and broadly applicable strategy to improve the cancer targeting efficiency and therapeutic effectiveness of polymeric nanomedicine.

Calcific aortic valve disease (CAVD) is the most frequent cardiac valve pathology. Its standard treatment consists of surgical replacement either with mechanical (metal made) or biological (animal tissue made) valve prostheses, both of which have glaring deficiencies. In the search for novel materials to manufacture artificial valve tissue, we have conducted a high-throughput screening with subsequent up-scaling to identify non-degradable polymer substrates that promote valve interstitial cells (VICs) adherence/growth and, at the same time, prevent their evolution toward a pro-calcific phenotype. Here, we provide evidence that one of the two identified ‘hit’ polymers, poly(methoxyethylmethacrylate- co -diethylaminoethylmethacrylate), provided robust VICs adhesion and maintained the healthy VICs phenotype without inducing pro-osteogenic differentiation. This ability was also maintained when the polymer was used to coat a non-woven poly-caprolactone (PCL) scaffold using a novel solvent coating procedure, followed by bioreactor-assisted VICs seeding. Since we observed that VICs had an increased secretion of the elastin-maturing component MFAP4 in addition to other valve-specific extracellular matrix components, we conclude that valve implants constructed with this polyacrylate will drive the biological response of human valve-specific cells.

Metabolic syndrome (MetS) includes central obesity, hypertension, insulin resistance, and dyslipidemia and is closely related to nonalcoholic fatty liver disease, atherosclerotic cardiovascular disease (CVD) and type 2 diabetes mellitus, involving multiple causative factors. Current drug therapies for intervention and amelioration of MetS are essential in clinical treatment of metabolic disease. In this report, we proposed an H + -modified montmorillonite (H-MMT) using an acid modification method with ultrafine structure and super absorption ability as a potential drug for MetS. Hamsters fed a high-fat diet were orally treated with H-MMT and simvastatin was applied as a control. H-MMT lowered lipids by decreasing intestinal absorption and promoting lipid excretion, subsequently preventing obesity, fatty liver, and hyperlipidemia. Moreover, H-MMT was significantly safer and better tolerated by the liver compared to simvastatin, which was hepatotoxic. In addition, we found that H-MMT had protective effects on gastric mucosal damage. Therefore, this versatile H-MMT provides a potential strategy to effectively improve MetS and provide gastric mucosal protection in clinical applications.

Biothiols such as cysteine (Cys), homocysteine (Hcy) and glutathione (GSH) play important roles in various physiological and pathological processes, and due to their similar structures and reaction activities, it is still challenging to simultaneously discriminate between GSH and Cys/Hcy in vivo . Hence, a novel fluorescent probe for simultaneously discriminating GSH and Cys/Hcy in biological samples is highly desirable. Herein, we presented two enhanced fluorescent probes (Cy1 and Cy2) with doubly-activated dual emission for sensitive and discriminative detection of Cys/Hcy and GSH. The probes were constructed with IR-780 and NBD linked via an ether bond, which responds to GSH with near infrared (NIR) emission at 810 nm ( λ ex = 720 nm) and Cys/Hcy with visible green emission at 550 nm ( λ ex = 470 nm). The probe Cy2 is operable in human serum samples, thus holding promise for its diagnosis-related application. Notably, the results of fluorescence microscopy imaging indicated that Cy2 is suitable for visualization of exogenous and endogenous biothiols in living cells. Furthermore, desirable results were obtained when the probe Cy2 was applied for bioimaging in tumor-bearing mice and acute liver injury (ALI) mice models, which revealed encouraging clinical values of this probe.

Introducing hydroxylapatite (HAp) into biomolecular materials is a promising approach to improve their bone regenerative capability. Thus a facile method needs to be developed to achieve this goal. Here we show that a simple air-plasma treatment of silk fibroin (SF) films for 5 min induced the formation of bone-like plate-shaped nano-HAp (nHAp) on their surface and the resultant material efficiently enhanced in vivo osteogenesis. The air-plasma-treated SF films (termed A-SF) presented surface nano-pillars and enhanced hydrophilicity compared to the pristine SF films (termed SF), making the A-SF and SF films induce the formation of plate-shaped/more-crystalline and needle-like/less-crystalline nHAp, respectively. The mineralized A-SF and SF films (termed A-SF-nHAp and SF-nHAp, respectively) and their non-mineralized counterparts were seeded with rat mesenchymal stem cells and subcutaneously implanted into the rat models. The A-SF-nHAp and A-SF films exhibited more efficient bone formation than the SF-nHAp and SF films in 4 weeks due to their unique nanotopography, with the A-SF-nHAp films being more efficient than the A-SF films. This work shows that a combination of the air-plasma treatment and the subsequent nHAp mineralization most efficiently promotes bone formation. Our plasma-based method is an attractive approach to enhance the bone regenerative capacity of protein-based biomaterials.