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      Mesoporous silica nanoparticles/gelatin porous composite scaffolds with localized and sustained release of vancomycin for treatment of infected bone defects

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          Abstract

          A highly porous composite scaffold with localized and sustained antibiotic release property for treatment of infected bone defects.

          Abstract

          Treatment of infected bone defects still remains a formidable clinical challenge, the design of bone implants with the controlled release of antibiotics is now regarded as a powerful strategy for infection control and bone healing. In this study, we fabricated a composite scaffold based on vancomycin (Van) loaded mesoporous silica nanoparticles (Van@MSNs) and a gelatin matrix. The microscopic structure of the gelatin-based composite scaffolds was characterized as highly porous. By the addition of MSNs, an enhancement in the compression property of MSNs-incorporated composite scaffolds was observed. The Van could release from the Van@MSNs incorporated composite scaffold in a sustained-release manner with a minimal burst, and thus effectively inhibit the growth of Staphylococcus aureus in a subsequent in vitro antibacterial study. In addition, the drug-loaded composite scaffold showed no unfavorable effects on the proliferation and differentiation of bone mesenchymal stem cells (BMSCs), confirming good biocompatibility. Moreover, in vivo results demonstrated that the antibiotic-loaded composite scaffold could significantly reduce bacterial contamination while promoting bone healing. Thus, our results suggest that the fabricated Van@MSNs/Gelatin composite scaffold with a localized and sustained release of antibiotics is a promising biomaterial for treating infected bone defects.

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          Most cited references 38

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          Fabrication and characterization of novel nano-biocomposite scaffold of chitosan-gelatin-alginate-hydroxyapatite for bone tissue engineering.

          A novel nano-biocomposite scaffold was fabricated in bead form by applying simple foaming method, using a combination of natural polymers-chitosan, gelatin, alginate and a bioceramic-nano-hydroxyapatite (nHAp). This approach of combining nHAp with natural polymers to fabricate the composite scaffold, can provide good mechanical strength and biological property mimicking natural bone. Environmental scanning electron microscopy (ESEM) images of the nano-biocomposite scaffold revealed the presence of interconnected pores, mostly spread over the whole surface of the scaffold. The nHAp particulates have covered the surface of the composite matrix and made the surface of the scaffold rougher. The scaffold has a porosity of 82% with a mean pore size of 112±19.0μm. Swelling and degradation studies of the scaffold showed that the scaffold possesses excellent properties of hydrophilicity and biodegradability. Short term mechanical testing of the scaffold does not reveal any rupturing after agitation under physiological conditions, which is an indicative of good mechanical stability of the scaffold. In vitro cell culture studies by seeding osteoblast cells over the composite scaffold showed good cell viability, proliferation rate, adhesion and maintenance of osteoblastic phenotype as indicated by MTT assay, ESEM of cell-scaffold construct, histological staining and gene expression studies, respectively. Thus, it could be stated that the nano-biocomposite scaffold of chitosan-gelatin-alginate-nHAp has the paramount importance for applications in bone tissue-engineering in future regenerative therapies.
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            Transcriptional regulatory cascades in Runx2-dependent bone development.

             Bonita Lee,  Lu T. Liu (2013)
            The development of the musculoskeletal system is a complex process that involves very precise control of bone formation and growth as well as remodeling during postnatal life. Although the understanding of the transcriptional mechanisms of osteogenesis has increased considerably, the molecular regulatory basis, especially the gene regulatory network of osteogenic differentiation, is still poorly understood. This review provides the reader with an overview of the key transcription factors that govern bone formation, highlighting their function and regulation linked to Runt-related transcription factor 2 (Runx2). Runx2 as the master transcription factor of osteoblast differentiation, Twist, Msh homeobox 2 (Msx2), and promyelocytic leukemia zinc-finger protein (PLZF) acting upstream of Runx2, Osterix (Osx) acting downstream of Runx2, and activating transcription factor 4 (ATF4) and zinc-finger protein 521 (ZFP521) acting as cofactors of Runx2 are discussed, and their relevance for tissue engineering is presented. References are provided for more in-depth personal study.
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              Antibiotic-eluting medical devices for various applications.

              Infection is defined as a homeostatic imbalance between the host tissue and the presence of microorganisms. It is associated with a large variety of wound occurrences ranging from traumatic skin tears and burns to chronic ulcers and complications following surgery and device implantations. If the wound setting manages to overcome the microorganism invasion by a sufficient immune response then the wound should heal. If not, the formation of an infection can seriously limit the wound healing process. Evidence of increasing bacterial resistance is on the rise, and complications associated with infections are therefore expected to increase. The main goal in treating various types of wound infections is to decrease the bacterial load in the wound to a level that enables wound healing processes to take place. Conventional systemic delivery of antibiotics entails poor penetration into ischemic and necrotic tissue and can cause systemic toxicity with associated renal and liver complications, which result in a need for hospitalization for monitoring. Alternative local delivery of antibiotics by either topical administration or by a delivery device may enable the maintenance of a high local antibiotic concentration for an extended duration of release without exceeding systemic toxicity. The present review describes approaches for local prevention of bacterial infections based on antibiotic-eluting medical devices. These devices include bone cements, fillers and coatings for orthopedic applications, wound dressings based on synthetic and natural polymers, intravascular devices, vascular grafts and periodontal devices. Part of the review is dedicated to our novel composite drug-eluting fibers and structured drug-eluting films, which are designed to be used as basic elements of various devices. In this review emphasis is placed on processing techniques, microstructure, drug release profiles, biocompatibility and other relevant aspects necessary for advancing the therapeutic field of antibiotic-eluting devices.
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                Author and article information

                Contributors
                Journal
                JMCBDV
                Journal of Materials Chemistry B
                J. Mater. Chem. B
                Royal Society of Chemistry (RSC)
                2050-750X
                2050-7518
                2018
                2018
                : 6
                : 5
                : 740-752
                Affiliations
                [1 ]College of Chemistry
                [2 ]Chemical Engineering and Biotechnology
                [3 ]State Key Laboratory for Modification of Chemical Fibers and Polymer Materials
                [4 ]Donghua University
                [5 ]Shanghai 201620
                [6 ]Department of Orthopaedics Trauma
                [7 ]Changhai Hospital
                [8 ]Second Military Medical University
                [9 ]Shanghai 200433
                [10 ]P. R. China
                [11 ]Department of Radiology
                [12 ]Shanghai East Hospital
                [13 ]Tongji University School of Medicine
                [14 ]Shanghai 200120
                Article
                10.1039/C7TB01246B
                © 2018
                Product
                Self URI (article page): http://xlink.rsc.org/?DOI=C7TB01246B

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