Xinyuan Xu

Antibacterial and anti-biofouling coating on hydroxyapatite surface based on peptide-modified tannic acid

Hydroxyapatite-based implant is widely used in the fields of artificial teeth and bones. However, the problem of microbial communities on hydroxyapatite surfaces remain a great challenge. In order to inhibit bacterial adhesion and activity in a long term, a salivary acquired pellicle (SAP) bioinspired tannic acid (SAP3-TA) is synthesized and characterized. The SAP inspired peptide sequence DDDEEK has a good adsorption performance on the surface of hydroxyapatite (HA). Tannic acid (TA) is a natural polyphenolic compound that can be extracted from green tea, and it has been proved to have an effective antibacterial property. After the coating of SAP3-TA on HA slices, the water contact angle is decreased to 14.2° and the HA surface becomes super-hydrophilic. The hydrophilic surface can prevent proteins adhesion and further inhibit the adhesion of bacteria. In this work, Streptococcus mutans (S. mutans) and bovine serum albumin (BSA) are used as models to prove the antibacterial and anti-biofouling properties of SAP3-TA coating on HA surface, respectively. SAP3-TA also shows low cytotoxicity to MG63 cells in the MTT test. All these results indicate that the SAP3-TA can be used as a potential antibacterial and anti-biofouling coating for hydroxyapatite-based implants.

Advances in polymeric materials for dental applications

Over the past decade, polymeric materials for clinical dental applications have been developed with excellent properties and various functionalities. This review outlines the present understanding and design of polymeric dental materials based on structure–property–function relationships. First, the chemistry/microstructure of polymeric materials will be reviewed. Then, the resultant properties such as mechanical, thermal, visco-elastic, and water solution properties, as well as additional bio-functionalities such as antibacterial capabilities, remineralization, and bioactive-delivery properties, will be reviewed for specific dental applications. Finally, perspectives and challenges regarding the rational design and application of polymeric dental materials will be discussed.

Effective in situ repair and bacteriostatic material of tooth enamel based on salivary acquired pellicle inspired oligomeric procyanidins

Remineralization and reduction of cariogenic bacteria at the tooth surface are effective ways to treat dental caries. In this work, a type of in situ repair and bacteriostatic material, i.e., salivary acquired pellicle inspired oligomeric procyanidins (SAP-OPC), was prepared for tooth enamel. Oligomeric procyanidins (OPC), as the active ingredient of grape seed extract, has good remineralization ability and bacteriostatic effects. The peptide sequence DDDEEKC, which has strong adsorption ability on hydroxyapatite (HA), is inspired by the sequence of statherin in the salivary acquired pellicle (SAP). Thus, SAP-OPC has the capability to tightly adsorb on the enamel surface, then repair the tooth decay and inhibit the growth of biofilm of cariogenic bacteria. We mainly explored the relationship between the remineralization property and aggregation morphology of SAP-OPC, and evaluate the anti-bacterial adhesion ability of the SAP-OPC coating. The acid-etched enamel was treated by SAP-OPC and SAP-OPC/Fe(III) and then incubated in artificial saliva. After 2 weeks, the HA mineralized layer was regenerated significantly on the surface of acid-etched enamel samples, and the hardness of the samples recovered to 61.6% and 76.8%, respectively. Also, SAP-OPC exhibited good antibacterial adhesive effects in the bacteriological test. In summary, SAP-OPC has good performance as restorative biomaterials to resist bacteria and also induce the remineralization of tooth enamel.

Thermoresponsive hydrogels based on a phosphorylated star-shaped copolymer: mimicking the extracellular matrix for in situ bone repair

A type of four-arm star-shaped copolymer (star-PAA(PEA)-PNIPAM), consisting of the thermoresponsive block (poly(N-isopropylacrylamide), PNIPAM) and the phosphorylated functional block O-phosphoethanolamine (PEA) grafted poly(acrylic acid) (PAA(PEA)), is synthesized by atom transfer radical polymerization (ATRP) and subsequent modification. Owing to the unique superiority of the star-shaped structure, star-PAA(PEA)-PNIPAM can transform from the sol to gel state in response to the physiological temperature (37 °C) at a relatively low polymer concentration (>0.5 wt%). In addition, because of the enriched phosphorylated functional groups, the hydrogel formed by star-PAA(PEA)-PNIPAM can mimic the acidic extracellular matrix protein to adsorb calcium ions and mineralize in situ, both in in vitro and in in vivo experiments. Meanwhile, it is favorable for cell adhesion and proliferation due to its appropriate three-dimensional interspace. Thus, the biocompatible star-PAA(PEA)-PNIPAM hydrogel has great potential for bone repair applications.

Bio-inspired peptide decorated dendrimers for a robust antibacterial coating on hydroxyapatite

Bacterial colonization on implanted biomaterials remains a clinically significant problem. In order to achieve relatively long-term antibacterial activity and reduce the incidence of infections associated with the use of biomaterials, a salivary statherin protein (SSP) inspired poly(amidoamine) dendrimer (SSP-PAMAM-NH2) was synthesized and characterized. PAMAM-NH2 has numerous peripheral amino groups, and thus possesses effective antibacterial activity. The SSP bio-inspired peptide sequence DDDEEKC was conjugated to PAMAM-NH2 since it has a strong capability of adsorbing on hydroxyapatite (HA). Moreover, SSP-PAMAM-NH2 is a zwitterionic polymer possessing cationic amino groups and anionic carboxylic groups, thus it can form aggregates by intermolecular electrostatic interactions, thereby promoting its adsorption on HA. Adsorption tests by ATR-IR, UV, QCM-D, and CLSM, all indicated that SSP-PAMAM-NH2 can tightly adsorb on the HA surface. We found that even after being incubated in PBS for 4 weeks, the SSP-PAMAM-NH2 treated HA disks still retained stable antibacterial activity, while the inhibitory impact of PAMAM-NH2 treated disks had disappeared. Animal experiments also demonstrated that SSP-PAMAM-NH2 could significantly reduce infection of HA implanted into the medullary cavity of rats.

Calcitonin-Loaded Thermosensitive Hydrogel for Long-Term Antiosteopenia Therapy

Effective antiosteopenia therapy can be achieved by designing long-term protein/peptide drug delivery systems for bone trabecula restoration. Here we show that a complex of salmon calcitonin and oxidized calcium alginate (sCT-OCA) was prepared and loaded into a thermosensitive copolymer hydrogel for long-term antiosteopenia treatment. The triblock copolymer, poly(d,l-lactic acid-co-glycolic acid)-b-poly(ethylene glycol)-b-poly(d,l-lactic acid-co-glycolic acid) (PLGA-PEG-PLGA) exhibited sol-gel transition at body temperature. The sustained release of sCT from the in situ gelling system was determined by both the degradation of the hydrogel and the decomposition of the sCT-OCA complex. This system showed sustained effects in reducing serum calcium and bone trabecula reconstruction in the treatment of glucocorticoid-induced osteopenia in rats for approximately 30 days after a single subcutaneous injection, which may shed light on antiosteopenia therapy in the future.

Bioinspired heptapeptides as functionalized mineralization inducers with enhanced hydroxyapatite affinity

The regeneration of mineral crystals under physiological conditions is an efficient way to repair defects in hard tissues. To achieve robust mineralization on surfaces such as the tooth enamel, an inducer requires strong affinity with the substrates and should be able to induce mineralization. Thus far, most studies used a single molecule containing two components to realize the above functions separately, which might be troublesome to synthesize and purify. In this work, inspired by the statherin in the salivary acquired pellicle, we designed a simple peptide sequence, Asp-Asp-Asp-Glu-Glu-Lys-Cys (peptide-7), to accomplish the dual tasks of adsorption and mineralization on enamel surfaces. We speculate the calcium binding ability of the negatively charged carboxylic acid groups in the peptide itself contributes to the dual functions of peptide-7. In vitro and in vivo experiments demonstrated its excellent repair effect on enamel as compared to fluoride. More importantly, due to the strong affinity between peptides and hydroxyapatite, a compact mineralized crystal layer and a strong adhesion between the regenerated minerals and the bottom substrates were observed, similar to the effect induced by fluoride. This work sheds light on the interaction mechanism between peptide-7 and minerals. In addition, since it is safer than fluoride, peptide-7 may have potential applications in the repair of other hard tissues and the functionalization of biomaterials.

A stimuli-responsive insulin delivery system based on reversible phenylboronate modified cyclodextrin with glucose triggered host-guest interaction

ABSTRACT Injection of insulin is an effective therapy to treat most patients with the type I diabetes and some with type II diabetes. Additionally, the release of insulin under specific conditions has attracted widespread interest. In this study, a smart drug carrier that can release insulin depending on the changes in blood glucose levels was designed. Combining two popular molecules through facile synthetic processes, a drug carrier of reversible phenylboronate group modified cyclodextrin (&bgr;‐CD‐EPDME) was fabricated. The drug carrier is composed of cyclodextrin, which can encapsulate insulin, and phenylboronate, which is sensitive to the cis‐diols in some saccharides. Moreover, &bgr;‐CD‐EPDME can successfully encapsulate insulin and almost completely release insulin in the presence of glucose. The detached phenylboronic acid moiety triggered by glucose can attack the &bgr;‐CD cavity and form a host‐guest complex, which can force out the encapsulated insulin within the cavity. In addition, the insulin released from the &bgr;‐CD‐EPDME@Insulin complex retains its secondary structure, and the drug carrier has been proven to have low cytotoxicity. Thus, this safe and glucose‐responsive drug carrier shows the potential for use in the therapy of diabetes.

One-step phosphorylated poly(amide-amine) dendrimer loaded with apigenin for simultaneous remineralization and antibacterial of dentine

Dental caries, starting from demineralization of enamel and dentine, is closely related with acid-producing bacteria in oral cavity, for example, Streptococcus mutans. Remineralization is an efficient way to prevent the disease progression and facilitate the therapy of incipient caries. Therefore, for the purpose of effective dentine repair, remineralization and antibacterial should be combined simultaneously. However, most of the literatures only focus on one single aspect, while combing remineralization and antibacteria for dentine repair in one system is rarely reported. Here in this work, phosphoryl-terminated poly(amide-amine) dendrimers were loaded with apigenin, a water-nonsoluble drug antibacterial agains Streptococcus mutans. The apigenin-loaded dendrimers bind strongly with dentine, which further induce dentine tubules occlusion through mineralization in artificial saliva, and the release of apigenin can prevent further erosion of dentine by bacteria. Meanwhile, the phosphorylated dendrimers are easily prepared by one-step modification of poly(amide-amine) and exhibit good cytocompatibility. This strategy developed here can provide reference for the design of effective anti-caries materials.

Multifunctional Biomaterial Coating Based on Bio-Inspired Polyphosphate and Lysozyme Supramolecular Nanofilm

Current implant materials have widespread clinical applications together with some disadvantages, the majority of which are the ease with which infections are induced and difficulty in exhibiting biocompatibility. For the efficient improvement of their properties, the development of interface multifunctional modification in a simple, universal, and environmently benign approach becomes a critical challenge and has acquired the attention of numerous scientists. In this study, a lysozyme-polyphosphate composite coating was fabricated for titanium(Ti)-based biomaterial to obtain a multifunctional surface. This coating was easily formed by sequentially soaking the substrate in reduced-lysozyme and polyphosphate solution. Such a composite coating has shown predominant antibacterial activity against Gram-negative bacteria ( E. coli) and improved cell adhesion, proliferation, and differentiation, which are much better than those of the pure substrate. This facile modification endows the biomaterial with anti-infective and potential bone-regenerative performance for clinical applications of biomaterial implants.