Mani Diba

Electrophoretic Deposition of Chitosan Coatings Modified with Gelatin Nanospheres To Tune the Release of Antibiotics.

Orthopedic and dental implants are increasingly used in the medical field in view of their high success rates. Implant-associated infections, however, still occur and are difficult to treat. To combat these infections, the application of an active coating to the implant surface is advocated as an effective strategy to facilitate sustained release of antibacterial drugs from implant surfaces. Control over this release is, however, still a major challenge. To overcome this problem, we deposited composite coatings composed of a chitosan matrix containing gelatin nanospheres loaded with antibiotics onto stainless steel plates by means of the electrophoretic deposition technique. The gelatin nanospheres were distributed homogeneously throughout the coatings. The surface roughness and wettability of the coatings could be tuned by a simple adjustment of the weight ratio between the gelatin nanospheres and chitosan. Vancomycin and moxifloxacin were released in sustained and burst-type manners, respectively, while the coatings were highly cytocompatible. The antibacterial efficacy of the coatings containing different amounts of antibiotics was tested using a zone of inhibition test against Staphylococcus aureus, which showed that the coatings containing moxifloxacin exhibited an obvious inhibition zone. The coatings containing a high amount of vancomycin were able to kill bacteria in direct contact with the implant surface. These results suggest that the antibacterial capacity of metallic implants can be tuned by orthogonal control over the release of (multiple) antibiotics from electrophoretically deposited composite coatings, which offers a new strategy to prevent orthopedic implant-associated infections.

Highly Elastic and Self‐Healing Composite Colloidal Gels

Composite colloidal gels are formed by the pH-induced electrostatic assembly of silica and gelatin nanoparticles. These injectable and moldable colloidal gels are able to withstand substantial compressive and tensile loads, and exhibit a remarkable self-healing efficiency. This study provides new, critical insight into the structural and mechanical properties of composite colloidal gels and opens up new avenues for practical application of colloidal gels.

Exploiting Bisphosphonate-Bioactive-Glass Interactions for the Development of Self-Healing and Bioactive Composite Hydrogels

Hydrogels are widely recognized as promising candidates for various biomedical applications, such as tissue engineering. Recently, extensive research efforts have been devoted to the improvement of the biological and mechanical performance of hydrogel systems by incorporation of functional groups and/or inorganic particles in their composition. Bisphosphonates are a class of drugs, commonly used for treatment of osteoporosis, which exhibit a strong binding affinity for hydroxyapatite. In this study, the binding affinity of a bisphosphonate-functionalized polymer, hyaluronan, toward a bioactive glass (i.e., 45S5 Bioglass) is evaluated using force-distance measurements with atomic force microscopy. The strong interaction between bisphosphonate and bioactive glass is then exploited to develop organic-inorganic composite hydrogels and the viscoelastic and self-healing ability of these materials are investigated. Finally, the stability and mineralization behavior of these hydrogels are evaluated in simulated body fluid. Following this approach, injectable, bioactive and self-healing organic-inorganic composite hydrogels are produced, which mineralize abundantly and rapidly in simulated body fluid. These properties render these composite gels suitable for applications in bone-tissue engineering.

Gelatin Nanoparticles with Enhanced Affinity for Calcium Phosphate

Gelatin nanoparticles can be tuned with respect to their drug loading efficiency, degradation rate, and release kinetics, which renders these drug carriers highly suitable for a wide variety of biomedical applications. The ease of functionalization has rendered gelatin an interesting candidate material to introduce specific motifs for selective targeting to specific organs, but gelatin nanoparticles have not yet been modified to increase their affinity to mineralized tissue. By means of conjugating bone-targeting alendronate to biocompatible gelatin nanoparticles, a simple method is developed for the preparation of gelatin nanoparticles which exhibit strong affinity to mineralized surfaces. It has been shown that the degree of alendronate functionalization can be tuned by controlling the glutaraldehyde crosslinking density, the molar ratio between alendronate and glutaraldehyde, as well as the pH of the conjugation reaction. Moreover, it has been shown that the affinity of gelatin nanoparticles to calcium phosphate increases considerably upon functionalization with alendronate. In summary, gelatin nanoparticles have been developed, which exhibit great potential for use in bone-specific drug delivery and regenerative medicine.

Dual-functionalisation of gelatine nanoparticles with an anticancer platinum(II)–bisphosphonate complex and mineral-binding alendronate

In order to improve the efficacy of therapeutic systems to treat bone tumours, novel drug delivery vehicles should be developed that have strong and specific affinity to mineralised tissue and at the same time are able to release anticancer molecules locally in a controlled and sustained manner. Recently, we developed mineral-binding gelatine nanoparticles with enhanced affinity to calcium phosphate by conjugating alendronate (ALN) molecules onto their surface. Herein, we have enhanced the functionality of these nanoparticles by rendering them potentially therapeutically active via covalent linking of an anticancer platinum–bisphosphonate (Pt–BP) complex. Different functionalisation schemes and molar ratios between reactants were screened and the effective functionalisation of gelatine nanoparticles with Pt–BP (or with both Pt–BP and ALN) was assessed. Our results revealed that the degree of functionalisation could be tailored by varying the molar ratio of Pt–BP and ALN relative to glutaraldehyde used as crosslinker. A sustained and tunable release of platinum as a function of the initial Pt–BP/ALN/glutaraldehyde molar ratio was achieved for both Pt–BP- and dual-functionalised gelatine nanoparticles. Moreover, dual-functionalised gelatine nanoparticles also displayed a high affinity to hydroxyapatite-coated surfaces thanks to the presence of ALN. Summarising, it was demonstrated that mineral-binding gelatine nanoparticles can be loaded with tailored amounts of anticancer molecules, which may benefit the development of bone-seeking carriers for targeted delivery of drugs to treat bone tumours.

Silver-containing bioactive glasses for tissue engineering applications

Abstract: Bioactive glasses have shown promising results for tissue engineering applications. Specific metallic ions can be used for doping these materials to induce enhanced biological performance. Silver is an element well-known for its antibacterial properties. This chapter present an overview of Ag-doped bioactive glasses including their synthesis, properties and applications in tissue engineering. Moreover, the reported effects of Ag-doping on the properties of bioactive glasses are discussed.

Nanostructured raspberry-like gelatin microspheres for local delivery of multiple biomolecules

Multicompartment particles, which are particles composed of smaller building units, have gained considerable interest during the past decade to facilitate simultaneous and differential delivery of several biomolecules in various applications. Supercritical carbon dioxide (CO2) processing is an industrial technology widely used for large-scale synthesis and processing of materials. However, the application of this technology for production of multicompartment particles from colloidal particles has not yet been explored. Here, we report the formation of raspberry-like gelatin (RLG) microparticles composed of gelatin nanoparticles as colloidal building blocks through supercritical CO2 processing. We show that these RLG microparticles exhibit a high stability upon dispersion in aqueous media without requiring chemical cross-linking. We further demonstrate that these microparticles are cytocompatible and facilitate differential release of two different model compounds. The strategy presented here can be utilized as a cost-effective route for production of various types of multicompartment particles using colloidal particles with suitable interparticle interactions. STATEMENT OF SIGNIFICANCE Multicompartment particles have gained considerable interest during the past decade to facilitate simultaneous and differential delivery of multiple biomolecules in various biomedical applications. Nevertheless, common methods employed for the production of such particles are often complex and only offer small-scale production. Here, we report the formation of raspberry-like gelatin (RLG) microparticles composed of gelatin nanoparticles as colloidal building blocks through supercritical CO2 processing. We show that these microparticles are cytocompatible and facilitate differential release of two model compounds with different molecular sizes, promising successful applications in various biomedical areas. Summarizing, this paper presents a novel strategy that can be utilized as a cost-effective route for production of various types of multicompartment particles using a wide range of colloidal building blocks.

Electrophoretic Co-Deposition of Chitosan and Graphene Oxide Results in Antibacterial Coatings for Medical Applications

Chitosan – graphene oxide (GO) composite coatings intended for antibacterial applications were obtained by cathodic electrophoretic deposition (EPD) on stainless steel. The coatings were characterized using SEM, FTIR, contact angle and roughness measurements and by antibacterial studies against E.coli. The coating was observed to consist of a polymer matrix with embedded, agglomerated graphene oxide sheets. A decrease in bacteria cell viability of at least 50 % was measured on the chitosan – GO surface in comparison to uncoated stainless steel.

Fiber-reinforced colloidal gels as injectable and moldable biomaterials for regenerative medicine

Hydrogels are the preferred material choice for various strategies in regenerative medicine. Nevertheless, due to their high water content and soft nature, these materials are often mechanically weak, which limits their applicability. This study demonstrates mechanical reinforcement of colloidal gels at microscale using discrete polyester fibers, as confirmed by rheological, compression and nanoindentation tests. This reinforcement strategy results in injectable and moldable colloidal gels with improved mechanical performance. The fully organic gels presented here are cytocompatible and can maintain their mechanical integrity under physiological conditions. Consequently, these gels exhibit a strong potential for applications in tissue engineering and regenerative medicine.