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.

A novel, multi-barrier, drug eluting calcium sulfate/biphasic calcium phosphate biodegradable composite bone cement for treatment of experimental MRSA osteomyelitis in rabbit model.

This article discloses the development of an effective and versatile technology to prepare a novel antibiotics-loaded biodegradable composite bone cement to treat methicillin-resistant Staphylococcal (MRSA) osteomyelitis and reports its detail in vitro characterization, drug loading efficiency, physico-mechanical properties, drug elution in simulated body fluid (SBF) and human plasma, merits and demerits over poly-methyl methacrylate (PMMA) cement. Chronic osteomyelitis in rabbit tibia (42) was induced by MRSA and composite cement was implanted to evaluate its safety and efficacy over PMMA cement and parenteral treated animals with histopathology, radiographs, bone/plasma drugs concentration, and SEM for 90days. The composite cement showed higher setting time, degradability, pH rise, injectability, in vitro drug elution but lesser mechanical strength than PMMA cement. Antibiotics release from cement beads was faster in SBF than plasma. Further, in vivo antibiotics elution from composite (42days) showed effective concentration against MRSA without eliciting drug-toxicity. Platelets activation by composite was an extraordinary feature. The in vivo studies also proved the superiority of composite cement than other treatment methods in terms of faster infection control and osteosynthesis. Based particularly on drug elution and in vivo results, this newly developed cement can successfully be used in clinical cases of chronic osteomyelitis.

Profilometric analysis of root surfaces after using various polishing agents.

BACKGROUND: Polishing is an important step in oral prophylaxis procedure which retards further accumulation of plaque on the root surfaces. Though polishing was done with various abrasive particles with different sizes over a long period of time, it was never been highlighted to evaluate the ideal polishing material and the particle size that would produce the ideal surface smoothness (Ra <0.2 µm). MATERIALS AND METHODS: The present study was carried out on 70 periodontally involved, caries-free extracted human teeth from 42 patients. All the teeth were collected from the region of incisors, canines, and premolars. In vitro scaling and root planing were performed by piezoelectric scaler and Gracey's area specific curettes, respectively. All the teeth were grouped at random into control and experimental. The collections of abrasive materials were done directly from the market, and the different particle sizes were prepared in the laboratory. EXPERIMENTATION: The polishing was done at a constant speed of 200 rpm with cylindrical nylon bristle brush followed by rubber prophy cup. Each group belonging to control and experimental was subjected to profilometric study for evaluation of surface roughness. RESULTS: Regular polishing abrasives are not able to produce the surface smoothness of our desire level (i.e., Ra <0.2 µm), which can be achieved only by submicron-sized particles. CONCLUSION: Regular size polishing particles available in the market (>5 µm) are not able to produce the surface smoothness <0.2 µm. Only, submicron sized particles are able to produce the desired smoothness.

Clinical Outcome of Hydroxyapatite Coated, Bioactive Glass Coated, and Machined Ti6Al4V Threaded Dental Implant in Human Jaws: A Short-Term Comparative Study.

INTRODUCTION: Growing aspect of endosseous implant research is focused on surface modification of dental implants for the purpose of improving osseointegration. The aim of this study was to evaluate and compare the clinical outcome (ie, osseointegration) of hydroxyapatite coated, bioactive glass coated and machined titanium alloy threaded dental implants in human jaw bone after implantation. MATERIALS AND METHODS: One hundred twenty-six implants (45 hydroxyapatite coated, 41 bioactive glass coated, and 40 machined titanium implants) have been placed in incisor areas of 62 adult patients. Outcome was assessed up to 12 months after prosthetic rehabilitation using different clinical and radiological parameters. Surface roughness of failed implants was analyzed by laser profilometer. DISCUSSION: Hydroxyapatite and bioactive glass coating materials were nontoxic and biocompatible. Least marginal bone loss in radiograph, significantly higher (P < 0.05) interface radiodensity, and less interfacial gaps were observed in computed tomography with bioactive glass coated implants at anterior maxilla compared to other 2 types. CONCLUSION: Bioactive glass coated implants are equally safe and effective as hydroxyapatite coated and machined titanium implants in achieving osseointegration; therefore, can be effectively used as an alternative coating material for dental implants.

Safety and efficacy of additive and subtractive surface modification of Ti6Al4V endosseous implant in goat bone.

Growing interest of endosseous implant research is focused on surface modification to achieve early and strong osseointegration. The present study compared the behaviour of hydroxyapatite coated, zinc doped hydroxyapatite coated and hydrothermally treated titanium (Ti6Al4V) with machined Ti6Al4V implants (control) on osseointegration. The surface characterization and bacterial affinity test for implants were performed. Forty eight (48) cylinders (4 types in each animal) were placed in the humerus bone of 12 black Bengal goats. Bone-implant interface was examined with histological, radiological parameters and scanning electron microscopy on 42nd, 90th, and 180th day post-implantation. Surface roughness alterations of bone-detached implants with time were analyzed by non-contact profilometer. Push-out test (90th day) was performed to assess the strength of bony integration of implants. The coated implants revealed direct and early bone-implant contact but high bacterial affinity and coating resorption/cracks. Low bacterial affinity and strongest osseointegration was observed with hydrothermally treated implants. Poor bacterial affinity and delayed but strong fixation were evident with control implant. Based on the results of laboratory and animal experiments, we conclude that the hydrothermal modification of titanium implant is the more suitable way to achieve safe and effective osseointegration than the other three implant types for endosseous application.

Converted marine coral hydroxyapatite implants with growth factors: in vivo bone regeneration.

Herein we report rabbit model in vivo bone regeneration of hydrothermally converted coralline hydroxyapatite (HCCHAp) scaffolds without (group I) and with growth factors namely insulin like growth factor-1 (IGF-1) (group II) and bone morphogenetic protein-2 (BMP-2) (group III). All HCCHAp scaffolds have been characterized for phase purity and morphology before implantation. Calcined marine coral was hydrothermally converted using a mineralizer/catalyst to phase pure HAp retaining original pore structure and geometry. After sintering at 1250°C, the HCCHAp found to have ~87% crystallinity, 70-75% porosity and 2±0.5MPa compressive strength. In vitro growth factor release study at day 28 revealed 77 and 98% release for IGF-1 and BMP-2, respectively. The IGF-1 release was more sustained than BMP-2. In vivo bone healing of different groups was compared using chronological radiology, histological evaluations, scanning electron microscopy and fluorochrome labeling up to 90days of implantation. In vivo studies showed substantial reduction in radiolucent zone and decreased radiodensity of implants in group II followed by group III and group I. These observations clearly suggest in-growth of osseous tissue, initiation of bone healing and complete union between implants and natural bone in group II implants. A statistical score sheet based on histological observations showed an excellent osseous tissue formation in group II and group III scaffolds and moderate bone regeneration in group I scaffolds.

Development and effect of different bioactive silicate glass scaffolds: in vitro evaluation for use as a bone drug delivery system.

Local drug delivery systems to bone have attracted appreciable attention due to their efficacy to improve drug delivery, healing and regeneration. In this paper, development and characterization of new formulations of bioactive glass into a porous scaffold has been reported for its suitability to act as a drug delivery system in the management of bone infections, in vitro. Two new glass compositions based on SiO2-Na2O-ZnO-CaO-MgO-P2O5 system (BGZ and MBG) have been developed which after thorough chemical and phase evaluation, studied for acellular static in vitro bioactivity in SBF. Porous scaffolds made of these glasses have been fabricated and characterized thoroughly for bioactivity study, SEM, XRD, in vitro cytotoxicity, MTT assay and wound healing assay using human osteocarcoma cells. Finally, gatifloxacin was loaded into the porous scaffold by vacuum infiltration method and in vitro drug release kinetics have been studied with varying parameters including dissolution medium (PBS and SBF) and with/without impregnation chitosan. Suitable model has also been proposed for the kinetics. 63-66% porous and 5-50µm almost unimodal porous MBG and BGZ bioactive glass scaffolds were capable of releasing drugs successfully for 43 days at concentrations to treat orthopedic infections. In addition, it was also observed that the release of drug followed Peppas-Korsmeyer release pattern based on Fickian diffusion, while 0.5-1% chitosan coating on the scaffolds decreased the burst release and overall release of drug. The results also indicated that MBG based scaffolds were bioactive, biocompatible, noncytotoxic and exhibited excellent wound healing potential while BGZ was mildly cytotoxic with moderate wound healing potential. These results strongly suggest that MBG scaffolds appear to be a suitable bone drug delivery system in orthopedic infections treatment and as bone void fillers, but BGZ should be handled with caution or studied elaborately in detail further to ascertain and confirm the cytotoxic nature and wound healing potential of this glass.

Effects of bioactive glass, hydroxyapatite and bioactive glass - Hydroxyapatite composite graft particles in the treatment of infrabony defects.

BACKGROUND: Several synthetic alloplastic materials have been used in the past as an implant in infrabony defects with a goal to reconstruct the lost part of attachment apparatus via new osseous tissue formation. The present study was undertaken to evaluate and compare clinico-radiographically, the effect of bioactive glass (BG), hydroxyapatite (HA), and BG-HA composite bone graft particles in the treatment of human infra-bony periodontal defects. MATERIALS AND METHODS: Indigenous synthetic HA, BG, and BG-HA composite bone graft materials were developed in the laboratory. Twenty eight infrabony periodontal defects were equally distributed (i.e., seven defects) into four groups. The defects were treated separately with three types of graft materials and non-grafted manner (open flap debridement alone, control) to evaluate both the soft and hard tissue responses after six months of surgery. Evaluation was done by studying different parameters such as plaque index, gingival index, relative attachment level, probing pocket depth, and radiographic bone fill in Intra Oral Peri-Apical radiograph. RESULTS: The healing of defects was uneventful and free of any biological complications. The gain in relative attachment level, reduction of probing pocket depth, and bone fill was statistically significant in all four groups. BG and BG-HA synthetic bone graft implanted sites showed significant bone fill (P<0.05) than hydroxyapatite and unimplanted control sites. CONCLUSION: The performance of BG and its composite was better compared to HA and open flap debridement alone for the reconstruction of infrabony defects. The BG-HA composite particles may effectively be used as an alternative bone graft material for infrabony defects.

Indigenous hydroxyapatite coated and bioactive glass coated titanium dental implant system - Fabrication and application in humans.

BACKGROUND: The use of different bioactive materials as coating on dental implant to restore tooth function is a growing trend in modern Dentistry. In the present study, hydroxyapatite and the bioactive glass-coated implants were evaluated for their behavior in osseous tissue following implantation in 14 patients. MATERIALS AND METHODS: Bioactive glass and hydroxyapatite formulated and prepared for coating on Ti-6Al-4V alloy. Hydroxyapatite coating was applied on the implant surface by air plasma spray technique and bioactive glass coating was applied by vitreous enameling technique. Their outcome was assessed after 6 months in vivo study in human. RESULTS: Hydroxyapatite and bioactive glass coating materials were nontoxic and biocompatible. Uneventful healing was observed with both types of implants. CONCLUSION: The results showed bioactive glass is a good alternative coating material for dental implant.

Macro-to-micro porous special bioactive glass and ceftriaxone-sulbactam composite drug delivery system for treatment of chronic osteomyelitis: an investigation through in vitro and in vivo animal trial.

A systematic and extensive approach incorporating in vitro and in vivo experimentation to treat chronic osteomyelitis in animal model were made using antibiotic loaded special bioactive glass porous scaffolds. After thorough characterization for porosity, distribution, surface charge, a novel drug composite were infiltrated by using vacuum infiltration and freeze-drying method which was subsequently analyzed by SEM-EDAX and studied for in vitro drug elution in PBS and SBF. Osteomyelitis in rabbit was induced by inoculation of Staphylococcus aureus and optimum drug-scaffold were checked for its efficacy over control and parenteral treated animals in terms of histopathology, radiology, in vivo drug concentration in bone and serum and implant-bone interface by SEM. It was optimized that 60P samples with 60-65% porosity (bimodal distribution of macro- to micropore) with average pore size ~60 µm and higher interconnectivity, moderately high antibiotic adsorption efficiency (~49%) was ideal. Results after 42 days showed antibiotic released higher than MIC against S. aureus compared to parenteral treatment (2 injections a day for 6 weeks). In vivo drug pharmacokinetics and SEM on bone-defect interface proved superiority of CFS loaded porous bioactive glass implants over parenteral group based on infection eradication and new bone formation.

Local drug delivery system for the treatment of osteomyelitis: In vitro evaluation.

Local antimicrobial delivery is a potential area of research conceptualized to provide alternative and better methods of treatment for cases, as osteomyelitis where avascular zones prevent the delivery of drugs from conventional routes of administration. Drug-loaded polymers and calcium phosphates as hydroxyapatites have been tried earlier. Bioactive glasses are bone-filling materials used for space management in orthopedic and dental surgery. A new bioactive glass (SSS2) was synthesized and fabricated into porous scaffold with a view to provide prolonged local delivery of gatifloxacin and fluconazole as suitable for the treatment of osteomyelitis. The new SSS2 was characterized by Fourier transform infrared (FTIR) and X-ray diffraction (XRD) analyses. In addition, the bioactivity of the SSS2 glass and resulting scaffold was examined by in vitro acellular method and ascertained by FTIR and XRD. The pore size distribution was analysed by mercury intrusion porosimetry and the release of drugs from scaffolds were studied in vitro. The glass and the resulting scaffolds were bioactive indicating that they can bond with bone in vivo. The scaffolds were porous with pores predominantly in the range of 10-60 µm, released the drugs effectively for 6 weeks and deemed suitable for local delivery of drugs to treat osteomyelitis.

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.

Organic-inorganic composites for bone drug delivery.

This review paper attempts to provide an overview in the fabrication and application of organic-inorganic based composites in the field of local drug delivery for bone. The concept of local drug delivery exists for a few decades. However, local drug delivery in bone and specially application of composites for delivery of drugs to bone is an area for potential research interest in the recent time. The advantages attained by an organic-inorganic composite when compared to its individual components include their ability to release drug, adopting to the natural environment and supporting local area until complete bone regeneration, which make them carriers of interest for local drug delivery for bone.

The repair of segmental bone defects with porous bioglass: an experimental study in goat.

This study was exclusively conducted to evaluate healing of surgically created defects on the radius of adult Black Bengal goat after implantation of porous bioglass blocks and compare the process kinetics with normal healing. Twelve Black Bengal goats were divided randomly into two groups: control and experimental group implanted with bioglass blocks. Unicortical bone defects in radius were generated in all animals under aseptic condition. Local inflammatory reaction and healing of wound, radiological investigations, histological studies, oxytetracycline leveling and angiographic studies were performed up to 90th day post-operatively and compared with normal healing. It has been found that extensive new bone formation originating from host bone towards the implant whereas in control, the process was active from both the ends; the defect site appeared as homogenous nonfluorescent area. Thus, porous bioglass promoted bone formation over the entire extension of the defect independent of size of block in comparison to control group.

In vivo response of porous hydroxyapatite and beta-tricalcium phosphate prepared by aqueous solution combustion method and comparison with bioglass scaffolds.

Pure hydroxyapatite (HAp) and a biphasic calcium phosphate [containing 90% of beta-tri-calcium phosphate (beta-TCP) and 10% HAp] were tailored through an aqueous solution combustion synthesis. Porous struts were prepared using all the powders along with bioglass, a known bioactive material, and subsequently characterized. Sterilized struts were implanted to the lateral side of radius bone of 24 black Bengal goats of either sex, in which a blank hole was left unfilled in a group of six specimens to act as control. The bone formation response of the three implanting materials in vivo has been studied using scanning electron microscope and histological analysis in contrast with positive controls. Push-out tests were used to assess the mechanical strength at the bone-biomaterial interface. It was observed that interfacial response was strongly dependent on combinations of different physical and chemical parameters. The surface of beta-TCP exhibited similar characteristics of bone and was distinct from those of intervening apatite layer of bioglass. Lower bone ingrowth and reduced strength was observed with HAp compared to beta-TCP/bioglass-based implants. Bone formation response of the Ca-P material varied according to the composition of the implanting material, which could be tailored through this novel synthesis.

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 interests.