Influence of single and binary doping of strontium and lithium on in vivo biological properties of bioactive glass scaffolds

Effects of strontium and lithium ion doping on the biological properties of bioactive glass (BAG) porous scaffolds have been checked in vitro and in vivo. BAG scaffolds were prepared by conventional glass melting route and subsequently, scaffolds were produced by evaporation of fugitive pore formers. After thorough physico-chemical and in vitro cell characterization, scaffolds were used for pre-clinical study. Soft and hard tissue formation in a rabbit femoral defect model after 2 and 4 months, were assessed using different tools. Histological observations showed excellent osseous tissue formation in Sr and Li + Sr scaffolds and moderate bone regeneration in Li scaffolds. Fluorochrome labeling studies showed wide regions of new bone formation in Sr and Li + Sr doped samples as compared to Li doped samples. SEM revealed abundant collagenous network and minimal or no interfacial gap between bone and implant in Sr and Li + Sr doped samples compared to Li doped samples. Micro CT of Li + Sr samples showed highest degree of peripheral cancellous tissue formation on periphery and cortical tissues inside implanted samples and vascularity among four compositions. Our findings suggest that addition of Sr and/or Li alters physico-chemical properties of BAG and promotes early stage in vivo osseointegration and bone remodeling that may offer new insight in bone tissue engineering

Drug-eluting implants for osteomyelitis

Osteomyelitis, an inflammatory process accompanied by bone destruction, is caused by infective microorganisms. The high success rates of antimicrobial therapy by conventional routes of administration in controlling most infectious diseases have not yet been achieved with osteomyelitis for several reasons. Local and sustained availability of drugs have proven to be more effective in achieving prophylactic and therapeutic outcomes. This review introduces osteomyelitis-its prevalence and pathogenesis, the present options for drug delivery and their limitations, and the wide range of carrier materials and effective drug choices, with major focus on the pharmaceutical concepts involved in drug delivery system design and development. With increasing numbers of orthopedic surgeries and the advent of combination devices that provide support and deliver drugs, local drug delivery for osteomyelitis is a topic of importance for both social and commercial interest

Development of porous HAp and beta-TCP scaffolds by starch consolidation with foaming method and drug-chitosan bilayered scaffold based drug delivery system

The inability to maintain high concentrations of antibiotic at the site of infection for an extended period of time along with dead space management is still the driving challenge in treatment of osteomyelitis. Porous bioactive ceramics such as hydroxyapatite (HAp) and beta-tri calcium phosphate (beta-TCP) were some of the alternatives to be used as local drug delivery system. However, high porosity and high interconnectivity of pores in the scaffolds play a pivotal role in the drug release and bone resorption. Ceftriaxone is a cephalosporin that has lost its clinical popularity. But has recently been reported to exhibit better bactericidal activity in vitro and reduced probability of resistance development, in combination with sulbactam, a beta-lactamase inhibitor. In this article, a novel approach of forming HAp and pure beta-TCP based porous scaffolds by applying together starch consolidation with foaming method was used. For the purpose, pure HAp and beta-TCP were prepared in the laboratory and after thorough characterization (including XRD, FTIR, particle size distribution, etc.) the powders were used for scaffold fabrication. The ability of these scaffolds to release drugs suitably for osteomyelitis was studied in vitro. The results of the study indicated that HAp exhibited better drug release profile than beta-TCP when drug was used alone indicating the high influence of the carrier material. However, this restriction got relaxed when a bilayered scaffold was formed using chitosan along with the drug. SEM studies along with EDAX on the drug-chitosan bilayered scaffold showed closest apposition of this combination to the calcium phosphate surface

Porous Bioactive Glass Scaffolds for Local Drug Delivery in Osteomyelitis: Development and In Vitro Characterization

A new bioactive glass-based scaffold was developed for local delivery of drugs in case of osteomyelitis. Bioactive glass having a new composition was prepared and converted into porous scaffold. The bioactivity of the resulting scaffold was examined by in vitro acellular method. The scaffolds were loaded with two different drugs, an antibacterial or antifungal drug. The effects of the size of the scaffold, drug concentration, and dissolution medium on drug release were studied. The scaffolds were further coated with a degradable natural polymer, chitosan, to further control the drug release. Both the glass and scaffold were bioactive. The scaffolds released both the drugs for 6 weeks, in vitro. The results indicated that the bigger the size and the higher the drug concentration, the better was the release profile. The scaffolds appeared to be suitable for local delivery of the drugs in cases of osteomyelitis

Vancomycin containing PLLA/β-TCP controls experimental osteomyelitis in vivo

BACKGROUND: Implant-related osteomyelitis (IRO) is recently controlled with local antibiotic delivery systems to overcome conventional therapy disadvantages. In vivo evaluation of such systems is however too little. QUESTIONS/PURPOSES: We asked whether vancomycin (V)-containing poly-l-lactic acid/β-tricalcium phosphate (PLLA/β-TCP) composites control experimental IRO and promote bone healing in vivo. METHODS: Fifty-six rats were distributed to five groups in this longitudinal controlled study. Experimental IRO was established at tibiae by injecting methicillin-resistant Staphylococcus aureus (MRSA) suspensions with titanium particles in 32 rats. Vancomycin-free PLLA/β-TCP composites were implanted into the normal and infected tibiae, whereas V-PLLA/β-TCP composites and coated (C)-V-PLLA/β-TCP composites were implanted into IRO sites. Sham-operated tibiae established the control group. Radiological and histological scores were quantified with microbiological findings on weeks 1 and 6. RESULTS: IRO is resolved in the CV- and the V-PLLA/β-TCP groups but not in the PLLA/β-TCP group. MRSA was not isolated in the CV- and the V-PLLA/β-TCP groups at all times whereas the bacteria were present in the PLLA/β-TCP group. Radiological signs secondary to infection are improved from 10.9 ± 0.9 to 3.0 ± 0.3 in the V-PLLA/β-TCP group but remained constant in the PLLA/β-TCP group. Histology scores are improved from 24.7 ± 6.5 to 17.6 ± 4.8 and from 27.6 ± 7.9 to 32.4 ± 8.9 in the CV-PLLA/β-TCP and the V-PLLA/β-TCP groups, respectively. New bone was formed in all the PLLA/β-TCP group at weeks 1 and 6. CONCLUSIONS: CV- and V-PLLA/β-TCP composites controlled experimental IRO and promoted bone healing. CLINICAL RELEVANCE: CV- and V-PLLA/β-TCP composites have the potential of controlling experimental IRO and promoting bone healing

Insights on the properties of levofloxacin-adsorbed Sr- and Mg-doped calcium phosphate powders

Several types of biodegradable materials have been investigated for the treatment of osteomyelitis. Calcium phosphate (CaP) ceramics are among the most performing materials due to their resemblance to human hard tissues in terms of mineralogical composition, and proven ability to adsorb and deliver a number of drugs. This research work was intended to study the suitability of modified CaP powders loaded with a fluoroquinolone as drug delivery systems for osteomyelitis treatment. Levofloxacin (LEV) was chosen due to the well-recognized antistaphylococcal activity and adequate penetration into osteoarticular tissues. Substituted CaP powders (5 mol% Sr2+ or 5 mol% Mg2+) were synthesised through aqueous precipitation. The obtained powders were characterised by X-ray diffraction, SEM and FTIR analysis. The X-ray diffraction patterns confirmed the presence of HA and beta-tricalcium phosphates (beta-TCP) phases in doped compositions, especially in the case of Mg-doped system. The fixation of LEV at the surface of the particles occurred only by physisorption. Both the in vitro microbiological susceptibility, against Staphylococcus spp, and biocompatibility of LEV-loaded CaP powders have not been compromised

Bioactive glass particles as multi‐functional therapeutic carriers against antibiotic‐resistant bacteria

The development of antibiotic resistance in pathogenic bacteria like Staphylococcus aureus calls for novel approaches to cope with the limited availability of effective antibacterial options. This work aims to develop a site- specific drug- delivery multifunctional vehicle with the ability to clear resistant bacteria while promoting the healing of the surrounding damaged tissue. The use of silver- doped microparticles (Ag- BG) is proposed as a platform to deliver vancomycin against MRSA, which under growth- arrested conditions exhibits resistance to vancomycin. Ag- BG caged vancomycin within the Ca- P deposits resulted from the ion exchange between surface and medium, with a loading efficiency higher than 50% after 6 h of uptake. The drug was always released above the minimum inhibitory concentration against MRSA. The Ag- BG@vanc conjugate presented strong antibacterial properties against metabolically impaired bacteria, which can tolerate high concentrations of vancomycin. Ag- BG@vanc was more lethal for MRSA than Ag- BG alone, due to its capability to synergize with antibiotics. The presence of Ca- P deposits and antibiotics at the Ag- BG surface did not compromise its biological properties since the Ag- BG@vanc conjugate still promoted the cell proliferation of human pre- osteoblast cells. These properties of multifunctional Ag- BG@vanc can provide new hope to fight antibiotic resistance and simultaneously promote bone regeneration holding great potential.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/171517/1/jace17923_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/171517/2/jace17923.pd