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Guided bone regeneration (GBR) is a surgical procedure utilizing occlusive membranes for providing space maintenance and enabling selective repopulation of the damaged area. While this technique is effective in regenerating bone, bacterial infiltration occurs frequently and can compromise the regenerative outcome. In this study, the authors describe the development and characterization of a GBR membrane made of medical grade polycaprolactone (mPCL) electrospun fibers with antibacterial and immunomodulatory properties. This is achieved by the immobilization of the antibiotic azithromycin into the membrane via a solvent evaporation technique leading to a sustained release of the drug over 14 d. In vitro testing shows that this controlled release of azithromycin is proficient at inhibiting the growth of Staphylococcus aureus for 14 d. Implantation of azithromycin loaded mPCL membrane in a rodent calvarial defect induces macrophage polarization toward the M2 phenotype after one week and results in significantly more bone regeneration eight weeks post-surgery. The results suggest that this antibacterial membrane should be effective at preventing infection and also impacts on the macrophage polarization enhancing bone regeneration. The drug loading technique developed in this study is simple, effective with a strong potential for clinical translation and can be applied to different types of scaffolds and implants for applications in craniofacial and orthopedics applications.
A calcium phosphate coated polycaprolactone (mPCL-CaP) electrospun membrane loaded with azithromycin is developed for improving the clinical outcomes of bone regeneration. The sustained local delivery of azithromycin using mPCL-CaP membrane inhibits bacterial growth, and enhances bone regeneration by promoting transition of pro-inflammatory M1 macrophages to a reparative M2 phenotype.
Hierarchical assemblies of dissimilar block copolymers (BCPs) can reveal interesting perspectives on material properties and device performance by providing multiple functionalities. Up to now, hierarchical assemblies of BCPs have been mostly prepared by stepwise assembling methods, in which the first type of BCP nanodomains is used as predefined patterns to guide the second-level assembly of another BCP. On the other hand, single-step blending methods suffer from a dilemma in the creation of hierarchical patterns because blending dissimilar BCPs typically induces either macrophase separation of component BCPs or chain-level hybridization into a single morphology. The present study is designed to overcome this apparent dilemma in polymer blends by exploiting a solvent annealing method. In particular, hierarchically assembled spheres-in-lamellae structures from a solvent-annealed blended film of binary polystyrene-block-poly(2-vinylpyrdine) and polystyrene-block-poly(4-vinyl pyridine) micelles are prepared. The focus of the current study is to understand the different effects of solvent vapor on the component BCPs and the molecular mechanism for the one-step assembling process. By addressing this issue, the parallelism in the phase behavior of BCP micelles and inorganic nanoparticles is highlighted, the underlying physical processes of which could be suggested as a one-step assembly principle for hierarchical superstructures beyond the previously reported multistep methods.
Hierarchically assembled spheres-in-lamellae structures have been prepared from a solvent-annealed blended film of binary polystyrene-block-poly(2-vinylpyrdine) and polystyrene-block-poly(4-vinyl pyridine) micelles. In addressing the assembling mechanism, an interesting parallelism in the phase behavior of polymer micelles and inorganic nanoparticles is discovered, the underlying physical processes of which could be suggested as a one-step assembly principle for hierarchical superstructures.
Engineering bone tissue requires the generation of a highly organized vasculature. Cellular behavior is affected by the respective niche. Directing cellular behavior and differentiation for creating mineralized regions surrounded by vasculature can be achieved by controlling the pattern of osteogenic and angiogenic niches. This manuscript reports on engineering vascularized bone tissues by incorporating osteogenic and angiogenic cell-laden niches in a photocrosslinkable hydrogel construct. Two-step photolithography process is used to control the stiffness of the hydrogel and distribution of cells in the patterned hydrogel. In addittion, osteoinductive nanoparticles are utilized to induce osteogenesis. The size of microfabricated constructs has a pronounced effect on cellular organization and function. It is shown that the simultaneous presence of both osteogenic and angiogenic niches in one construct results in formation of mineralized regions surrounded by organized vasculature. In addition, the presence of angiogenic niche improves bone formation. This approach can be used for engineered constructs that can be used for treatment of bone defects.
Photocrosslinkable bicomponent hydrogel is an engineered 3D vascularized bone-like construct. Two-step photolithography process allows controlling the stiffness and distribution of cells in the patterned hydrogel. Incorporating nanoparticles can induce formation of mineralized regions surrounded by organized vasculature. This approach can be used to fabricate customized engineered constructs for treatment of bone defects.
Nature Materials. doi:10.1038/nmat4869
Authors: Étienne Ducrot, Mingxin He, Gi-Ra Yi & David J. Pine
Nature Materials. doi:10.1038/nmat4868
Authors: Timothée Mouterde, Gaëlle Lehoucq, Stéphane Xavier, Antonio Checco, Charles T. Black, Atikur Rahman, Thierry Midavaine, Christophe Clanet & David Quéré
Nature Materials. doi:10.1038/nmat4864
Authors: Paul E. Pearce, Arnaud J. Perez, Gwenaelle Rousse, Mathieu Saubanère, Dmitry Batuk, Dominique Foix, Eric McCalla, Artem M. Abakumov, Gustaaf Van Tendeloo, Marie-Liesse Doublet & Jean-Marie Tarascon
Nature Materials. doi:10.1038/nmat4863
Authors: L. Rossetti, L. A. Kuntz, E. Kunold, J. Schock, K. W. Müller, H. Grabmayr, J. Stolberg-Stolberg, F. Pfeiffer, S. A. Sieber, R. Burgkart & A. R. Bausch