The aim of the study was to assess an effectiveness of S53P4 bioglass in reconstruction of postinflammatory bone loss. We have also evaluated wound healing after the surgical dead space management with use of the bioglass. A group of 7 patients with bone loss due to active osteomyelitis and with purulent fistula treated with use of S53P4 bioglass is presented in the paper. All the treated patients were male with mean of age 40,5 years. Mean time of an active inflammatory process with purulent discharge from the wound prior the surgery was 587 weeks. Wound healing pattern with an X-ray evaluation of reconstructed void was performed in postoperative period as well as in 1, 3, 6 and 12 mounth follow-up. In 6 out of 7 cases we did not observed any signs of infection recurrence in 1-year follow-up. Starting from 1-month follow-up inflammatory serum markers remained in their reference values. In all the successfully treated cases wound healing was assessed by two independent surgeons as excellent or good. Starting from 3-month follow-up we have observed gradual blurring of granular bioglass structure on an X-ray scans. In 1 complicated case we observed recurrence of septic inflammatory process with purulent fistula that required revision procedure with removal of the bioglass and extended debridement of inflammatory focus. In this case we have faced posttraumatic malunion of the femur that substantially complicated surgical access to the inflammatory focus during primary procedure. S53P4 bioactive glass is an effective solution in reconstruction of postinflammatory bone loss. Properties of this biomaterial efficiently prevent from focal infection recurrence by inhibiting of bacterial bone growth and reduction of dead space. The product requires however meticulous debridement and the access to a vital bone as a source of osteoblast cells. Underestimation of surgical debridement will likely result in reopening of the fistula due to reinfection. The study group requires further evaluation

Musculoskeletal disorders is one of most important health problems human population is facing includes. Approximately 310 thousand of hip protheses have been used in 45 years and older patients in total according to the recent studies have been done. [1, 2]. Many factors, including poor osseointegration or relaxation of the implant due to stress, limit the life of the load-bearing implants [3]. To overcome these difficulties and to protect metal implants inside the body, the surfaces of the implants were coated with silver ion doped hydroxyapatite/bioglass. In this study, silver doped hydroxyapatite ceramic powder and 6P57 bioglass were synthesized. Two different coating suspensions, 100% bioglass and 70% Ag-HAp / 30% bioglass, were prepared in methyl alcohol with a solid content of 1% by weight. Two layers were coated on the external fixator nails by using electrospray method with the bioglass and Ag-Hap/Bioglass suspensions respectively. The coated implants were cut with an equal surface area and kept in human blood plasma for different time. The scanning electron microscopy (SEM, Zeiss Supra 50VP and Zeiss Evo 50EP) and stereo microscope (Zeiss Axiocam Stemi 2000-C) were used to characterize microstructure and thickness of coated surface. Energy dispersive X-ray Spectroscopy was used characterized of chemical composition of coating. Changing of pH value of plasma was measured by pH meter (Hanna HI83414). In addition, the ICP method was used to determine the elements contained in the plasma fluid after dissolution. As a result of this study, physical and chemical changes occurring on the coating surface in different time periods are presented in detail

Bioactive glasses, such as 45S5 Bioglass (BG), have been shown to promote bone ingrowth both in vitro and in vivo. The goal of this study was to analyze the effect of a high dose of BG (20%) in Direct Ink Writing (DIW)-produced controlled-geometry PCL-BG composite scaffolds in both their mechanical and biological performance. Porous cubes of 5 × 5 × 5 mm, 50% porosity and pore size and strut diameter of 400 µm were fabricated in a 3D-Bioplotter (EnvisionTec) to investigate their biological performance (n = 3). Additionally, cylindrical specimens (10 mm diameter; 15 mm height) with same internal structure were fabricated for mechanical testing (n = 6). The cylindrical specimens were tested by compression in a universal testing machine (ZwickRoell) with a 10 kN load cell. The tests were performed at 1.00 mm/min with extensometers in both sides. For biological characterization, scaffolds were sterilized in 70% ethanol overnight and pre-incubated with DMEM for 1 hour at room temperature. 1×10. 5. human gingival mesenchymal stem cells (hGMSCs) in 50 µl DMEM were seeded on the scaffolds using agarose molds to improve cell adhesion, and cultured in standard cell-culture conditions for 3, 7 and 14 days. To measure cell proliferation, the reagent CellTiter 96® AQueous One Solution Cell Proliferation Assay (MTS, Promega) was added to the cell-seeded scaffolds at each time point, using non-seeded scaffolds as blank controls. The OD (490 nm) was measured in a BioTek 800 TS plate reader. Both the apparent elastic modulus and yield stress were significantly lower in the scaffolds with 20% BG than their PCL control counterparts (p < 0.0001 for elastic modulus and p < 0.005 for yield stress, t-test). Cell proliferation in the scaffolds by MTS was variable, with the 20% BG scaffolds showing a significantly higher signal after seven days in culture (p < 0.05 by t-test), but a significantly lower signal after 14 days in culture (p < 0.05 by t-test). In conclusion, scaffolds with 20% BG showed a lower mechanical performance than their PCL counterparts in terms of both their apparent elastic modulus and yield stress. Additionally, scaffolds with 20% BG showed variable cell proliferation rates in terms of their metabolic activity over a two-week period. The decrease in proliferation rate after week 2 after an initial increase at the end of week 1 could be due to cytotoxic effects of the BG at this high dose (20%) after long term exposure. These results suggest that a dosage of 20% BG may not necessarily improve the mechanical and biological performance of scaffolds, so future experiments are required in order to characterize the optimum BG dosage in PCL scaffolds for tissue engineering applications

Aim. The treatment of osteomyelitis often requires extensive surgical debridement and removal of all infected tissues and foreign bodies. Resulting bone loss can then eventually be managed with antibacterial bone substitutes, that may also serve as a regenerative scaffold. Aim of the present study is to report the clinical results of a continuous series of patients, treated at our centre with an antibacterial bioglass*. Method. From November 2010 to May 2016, a total of 106 patients, affected by osteomyelitis, were included in this prospective, single centre, observational study. Inclusion criteria were the presence of osteomyelitis with a contained bone defect or segmental defects < 10 mm, with adequate soft tissue coverage. All patients underwent a one-stage procedure, including surgical debridement and bone void filling with the bioactive glass*, with systemic antibiotic therapy and no local antibiotics. Clinical, radiographic and laboratory examinations were performed at 3, 6 and 12 months and yearly thereafter. Results. Two patients were lost to follow-up, hence a total of 104 patients (65 males, 39 females; mean age: 46 ± 17 years, min 6 – max 81) were available at an average follow-up of 38 ± 26 months (range: 12 – 68); forty-eight patients (46.1%) were classified as Type A, 48 (46.1%) as Type B and 8 (7.7%) as Type C hosts, according to McPherson classification. Tibia (N=61) and femur (N=33) were the most common involved bones. On average patients had undergone 2.1 ± 1.3 (min 0 – max 7) previous surgical operations, with a mean infection duration of 18.7 ± 16.6 months (min 2 – max 120). Infection recurrence was observed in 10 patients (9.6%), most often within one year from surgery (8/10). Negative prognostic factors included infection duration > 2 years, Gram negative or mixed flora or negative cultural examination, Type B or C hosts and soft tissue defect. No side effects or complications related to bioglass were noted. Conclusions. This is to our knowledge the longest and the largest single centre consecutive series of patients, affected by bone infections of the long bones, treated according to a one-stage procedure using bioactive glass. Our results confirm, on a larger population and at a longer follow-up, previous reports. Early treatment, pathogen identification and adequate management of soft tissues should be considered to further reduce infection recurrence rate. *BonAlive®

Synthetic bone grafts are used in several major dental and orthopaedic procedures. Strontium, in the form of strontium ranelate, has been shown to reduce fracture risk when used to treat osteoporosis. The aim of the study was to compare bone repair in femoral condyle defects filled with either a 10% strontium substituted bioactive glass (StronBoneTM) or a TCP-CaSO4 graft. We hypothesise that strontium substituted bioactive glass increases the rate of bone ingrowth into a bone defect when compared to a TCP-CaSO4 ceramic graft. A critical size defect was created in the medial femoral condyle of 24 sheep; half were treated with a Sr-bioactive glass (StronBoneTM), and in the other animals defects were filled TCP-CaSO4. Two time points of 90 and 180 days were selected. The samples were examined with regard to: bone mineral density (BMD) from peripheral quantitative CT (pQCT), mechanical properties through indentation testing, and bony ingrowth and graft resorption through histomorphometry. The radiological density of Sr-bioactive glass in the defect is significantly higher than that of the TCP-CaSO4-filled defect at 90 and 180 days, (p=0.035 and p=0.000). At 90 days, the stiffness of the defect containing Sr-bioactive glass and is higher than that of the TCP-CaSO4 filled defect, (p=0.023). At 6 months there is no significant difference between the two materials. Histomorphometry showed no significant difference in bone ingrowth at any time point, however significantly more of the graft is retained for the StronBoneTM treatment group than the TCP-CaSO4 group at both 0 days (p=0.004) and 180 days (p=0.000). The amount of soft tissue within the defect was significantly less in the StronBoneTM group than for the TCP-CaSO4 group at 90 days (p=0.006) and 180 days (p=0.000). The data shows the mechanical stability of the defect site is regained at a faster rate with the strontium substituted bioglass than the TCP-CaSO4 alternative. Histomorphmetry shows this is not due to increased bone ingrowth but may be due to the incorporation of stiff graft particles into the trabeculae. Sr-bioactive glass produces a stronger repair of a femoral condyle defect at 3 months compared with TCP-CaSO4

Aim. Infections in long bones can be divided in osteitis, osteomyelitis and septic non-unions. All are challenging situations for the orthopaedic surgeon. Treatment is a mix with debridement, radical resection of infected tissue, void filling with different types of products, and antibiotic therapy of different kinds. In cavitary bone defects, bioglasses such as BAG-S53P4 have given good results in early or mid-term follow-up. Results of such treatment in segmental bone defects remain unknown. The goal of our study was to evaluate efficacity of active bioglass BAG-S53P4 in septic segmental bone defects. Method. A retrospective cohort study has been done in a single specific orthopaedic center devoted to treatment of infected bony situations. All cases were a severe septic bone defect. We have compared the segmental bone defects to the cavitary ones. Results were analyzed on recurrence of infection, bone healing, functional result and complication rate. Results. 14 patients were included with a minimum follow-up of 1 year after treatment. 8 were in the group “cavitary”, 6 in the group “segmental”. The mean age was 54 years-old (30–76). Sex-ratio was 2.5. All patients have been treated with bone resection and debridement of infected bone and tissue, even if more than 1 surgery was necessary in some cases. After cleaning, 7 patients have needed a local flap, and 1 a free flap. Then, all bone defects were filled up by bioglass BAG-S53P4*. Additional antibiotherapy with specific molecules based of the results of bacterial analysis, was given for a minimum time-period of 6 weeks. In the “cavitary” group, the mean volume of BAG-S53P4 was de 21.25 ml (10–60). In the “segmental” group, it was of 12.5 ml (10–20). The healing rate was of 80% in the “cavitary” group and of 100% in the “segmental” one. No complication related to the bioglass insertion was noted. Conclusions. Different publications have been made using bioglass in the treatment of infected bone with a continuous bone such as osteitis or osteomyelitis. Our study is the first one to compare specifically the results obtained in a cavitary defect where the bone is still in continuity, and in a segmental defect. Active bioglass such as the BAG-S53P4 seems to be a good option in the treatment of segmental septic bone defects in the limb. *BonAlive Biomaterials Ltd, Turku, Finland

Cartilage injuries often represent irreversible tissue damage because cartilage has only a low ability to regenerate. Thus, cartilage loss results in permanent damage, which can become the starting point for osteoarthritis. In the past, bioactive glass scaffolds have been developed for bone replacement and some of these variants have also been colonized with chondrocytes. However, the hydroxylapaptite phase that is usually formed in bioglass scaffolds is not very suitable for cartilage formation (chondrogenesis). This interdisciplinary project was undertaken to develop a novel slowly degrading bioactive glass scaffold tailored for cartilage repair by resembling the native extracellular cartilage matrix (ECM) in structure and surface properties. When colonized with articular chondrocytes, the composition and topology of the scaffolds should support cell adherence, proliferation and ECM synthesis as a prerequisite for chondrogenesis in the scaffold. To study cell growth in the scaffold, the scaffolds were colonized with human mesenchymal stromal cells (hMSCs) and primary porcine articular chondrocytes (pACs) (27,777.8 cells per mm. 3. ) for 7 – 35 d in a rotatory device. Cell survival in the scaffold was determined by vitality assay. Scanning electron microscopy (SEM) visualized cell ultramorphology and direct interaction of hMSCs and pACs with the bioglass surface. Cell proliferation was detected by CyQuant assay. Subsequently, the production of sulphated glycosaminoglycans (sGAGs) typical for chondrogenic differentiation was depicted by Alcian blue staining and quantified by dimethylmethylene blue assay assay. Quantitative real-time polymerase chain reaction (QPCR) revealed gene expression of cartilage-specific aggrecan, Sox9, collagen type II and dedifferentiation-associated collagen type I. To demonstrate the ECM-protein synthesis of the cells, the production of collagen type II and type I was determined by immunolabelling. The bioactive glass scaffold remained stable over the whole observation time and allowed the survival of hMSCs and pACs for 35 days in culture. The SEM analyses revealed an intimate cell-biomaterial interaction for both cell types showing cell spreading, formation of numerous filopodia and ECM deposition. Both cell types revealed initial proliferation, decreasing after 14 days and becoming elevated again after 21 days. hMSCs formed cell clusters, whereas pACs showed an even distribution. Both cell types filled more and more the pores of the scaffold. The relative gene expression of cartilage-specific markers could be proven for hMSCs and pACs. Cell associated sGAGs deposition could be demonstrated by Alcian blue staining and sGAGs were elevated in the beginning and end of the culturing period. While the production of collagen type II could be observed with both cell types, the synthesis of aggrecan could not be detected in scaffolds seeded with hMSCs. hMSCs and pACs adhered, spread and survived on the novel bioactive glass scaffolds and exhibited a chondrocytic phenotype

Introduction: New biological approaches to reconstruction of major bone deficiency such as the use of bone substitutes and growth factors are being developed. This paper reports on the adverse response to the Bioglass in comparison to allograft alone. Aim: To compare the biological response to femoral impaction grafting and a cemented femoral stem when using allograft bone versus allograft bone plus a synthetic bone graft substitute, Bioactive glass. Methods: Eighteen merino wethers underwent a left cemented hemi-arthroplasty and were randomised to have impaction allografting of the femur using either allograft alone (allograft group) or a 50:50 mix of allograft and Bioactive glass (Bioglass group). After sacrifice at 12 weeks, histological analysis of the femora at the levels of the proximal, mid and distal femoral stem and distal to the stem was undertaken. Results: In the allograft group, there was a consistent response with bone graft incorporation being greatest in the proximal femur and occurring progressively less, more distally. Mineralised bone apposition in the graft occurred post-operatively after eight weeks. In contrast, in the Bioglass group, the response was inconsistent. Bone graft incorporation was either minimal, or there was partial or complete resorption of the bone graft with replacement by particulate-laden fibrous tissue and resorption of endocortical bone. Inflammation of the capsule tissue was noted in some cases. Conclusion: In comparison to allograft alone, the use of Bioglass to supplement allograft for use in impaction grafting in ovine hip arthroplasty gave inferior results

Introduction and Objective. Bone is a tissue which continually regenerates and also having the ability to heal after injuries however, healing of large defects requires intensive surgical treatment. Bioactive glasses are unique materials that can be utilized in both bone and skin regeneration and repair. They are degradable in physiological fluids and have osteoconductive, osteoinductive and osteostimulative properties. Osteoinductive growth factors such as Bone Morphogenetic Proteins (BMP), Vascular Endothelial Growth Factor (VEGF), Epidermal Growth Factor (EGF), Transforming Growth Factor (TGF) are well known to stimulate new bone formation and regeneration. Unfortunately, the synthesis of these factors is not cost- effective and, the broad application of growth factors is limited by their poor stability in the scaffolds. Instead, it is wise to incorporate osteoinductive nanomaterials such as graphene nanoplatelets into the structures of synthetic scaffolds. In this study, borate-based 13-93B3 bioactive glass scaffolds were prepared by polymer foam replication method and they were coated with graphene-containing poly (ε-caprolactone) layer to support the bone repair and regeneration. Materials and Methods. Effects of graphene concentration (1, 3, 5, 10 wt%) on the healing of rat segmental femur defects were investigated in vivo using male Sprague–Dawley rats. Fabricated porous bioactive glass scaffolds were coated by graphene- containing polycaprolactone solution using dip coating method. The prepared 0, 1, 3, 5 and 10 wt% graphene nanoparticle-containing PCL-coated composite scaffolds were designated as BG, 1G-P-BG, 3G-P-BG, 5G-P-BG and 10G-P-BG, for each group (n: 4) respectively. Histopathological and immunohistochemical (bone morphogenetic protein, BMP-2; smooth muscle actin, SMA and alkaline phosphatase, ALP) examinations were made after 4 and 8 weeks of implantation. Results. Results showed that after 8-weeks of implantation both cartilage and bone formation were observed in all animal groups. After 4 and 8 weeks of implantation the both osteoblast and osteoclast numbers were significantly higher in the group 4 compared to the control group. Bone formation was significant starting from 1 wt% graphene-coated bioactive glass implanted group and highest amount of bone formation was obtained in group containing 10 wt% graphene (p<0.001). Newly formed vessels expressed this marker and increased vascularization was observed in 8- weeks period compared to the 4-weeks period. In addition, an increase in new vessel formation were observed in graphene-coated scaffold implanted groups compared to the control group. While cartilage tissue was observed in control group, bone formation percentages were significant in graphene-coated scaffold implanted groups. Highest amount of bone formation occurred in group 4 (10 % wt G-C). Conclusions. Additionally, the presence of graphene nanoplatelets enhanced the BMP-2, SMA and ALP levels compared to the bare bioactive glass scaffolds. It was concluded that pristine graphene-coated bioactive glass scaffolds improve osteointegration and bone formation in rat femur defect when compared to bare bioglass scaffolds

Introduction and Objectives: The coating of implants with biomaterials seems to be a step further toward the ideal biological integration of an inert implant in live recipient bone where it will be subjected to load and movement. The goal of this study is to present results from 70 hip prostheses with implantation of a bioglass-coated stem. Materials and Methods: The “Grupo para el Estudio del Biovidrio” [Group for the Study of Bioglass] and the Stazione del Vetro de Murano experimented with a biocompatible, osteoconductive bioglass in 1992, creating the Biovetro patent as the first bioglass used for the coating of the CRM total hip prosthesis (Seipi-Bio-implant). In 1992, implantation of this prosthesis was begun in Italy and Spain. In 1994 and 1995, we implanted 70 TiAlva CRM stem total hip prostheses with the proximal two-thirds coated with an 80-micron thick layer of Biovetro. A Ceraver-Osteal impacted cup covered with a titanium mesh was used in all cases. Results: Of the 70 CRM prostheses implanted, adequate clinical and radiographic examination was possible in 62 cases, with an 8-year follow-up time. Clinical evaluation was done using the Merle D’Aubigne Postel criteria: pain, mobility, and gait. In 77% of patients, results were excellent or good, while 23% had fair or poor results. Radiographic evaluation according to Engh’s criteria for cementless stems showed 56 (90%) stable stems, 1 (1.6%) unstable stem, and 5 (8%) stem revisions, in one case due to infection. Survival rate for this stem at 8 years was 91.4%. Discussion and Conclusions: Based on these results, we believe Biovetro coating produces worse osteointegration than HA due to: 1) Appearance of a fibrous interface with a macrophage foreign body reaction. 2) Less new bone formation activity and a significant delay in maturation. 3) Insufficient mineralization of newly-formed bone

Aim. Intramedullary osteomyelitis remains a challenge in the treatment of bone infections, requires organized, sequential and effective management to prevent its spread and subsequent recurrence. Errors are often made in the comprehensive treatment of this type of infection classified as type 1 of Cierny-Mader, where you can perform an insufficient treatment or in some cases perform very extensive and unnecessary bone resections. A rigorous protocol is proposed, by stages to achieve the total eradication of the infection and a surgical tactic that avoids diffusion of the infection or recurrences. Method. In the prospective case series study, 16 patients with type 1 intramedullary infection of Cierny Mader, diagnosed by radiology, TAC or MRI were included. The microbiological protocol is carried out, with the germ typing and the corresponding antibiogram, at least 3 samples of deep tissues, the biofilm and segments of dead bone are taken. In the surgical tactic, intramedullary sequestrations are resected, the intramedullary canal is cleaned by stages, initially in the most inflammatory focus detected, the medullary canal is accessed through a planned and defined bone window, with round edges to avoid fractures and allowing access To the flexible reamer and cleaning guides, an additional window is made that avoids the blood dissemination of the infection, the septic embolisms or the contamination of the underlying soft tissues. It is defined if it requires stabilization of the bone with internal or external devices, therapies are applied locally to avoid recolonization, using Bioglass or absorbable substitutes with selective antibiotic. The treatment is associated with intravenous antibiotic therapy between 2 and 6 weeks according to the type of germ and if it is multiresistant. It guarantees skin coverage and protection of structures at risk such as nerves, tendons and exposed bone. Results. Successful treatment results are obtained, infection eradication in 100% of cases, the healing of osteomyelitis is achieved by applying an integral management of the intramedullary canal Osteomyelitis and a complete protocol is established. Conclusions. The tactic and surgical technique applied in the integral management of intramedullary bone infection is essential to obtain definitive results in the eradication of bone infection. Care must be taken that the debridement is complete of the intramedullary canal and additionally, segmental or exaggerated resection of viable bone must be avoided, which survives and heals after the integral management of the infection with effective antibiotic therapy

Introduction and Aims: The usefulness of bone graft substitutes and growth factors to promote bone graft incorporation and prosthesis fixation in hip replacement should be examined in a loaded model, as results from cortical defect models may not apply. This paper reviews the results of femoral impaction grafting using these materials in an ovine hip replacement model. Method: At cemented hemiarthroplasty, sheep femurs were impacted with allograft bone (control group n=23) or with allograft mixed with: 1) corglaes bioglass (n=12); 2) a synthetic hydroxyapatite (HA) (n=6) or the bone morpohogenetic protein OP-1 (n=6) (study groups) and implanted with a cemented double taper femoral stem. Sheep were sacrificed at between six and 26 weeks. The primary outcome was femoral stem subsidence, as determined more recently by the development of clinical radiostereometric analysis (RSA) in this model. Femoral fixation, as assessed by ex-vivo mechanical testing, and bone graft incorporation, as assessed by histological review and histoquantitation, were also key outcomes. Results: In the control groups, there was a consistent response with bone graft incorporation by new bone advancing proximal to distally in the femur and advancing from the endocortex towards the cement mantle. Mineralised bone apposition occurred by six weeks and this was preceeded by partial resorption of the graft. Complete graft incorporation, with subsequent remodelling of bone, was evident proximally by 26 weeks. Bone graft incorporation in femurs impacted with a 1:1 allograft: bioglass mix was minimal and there was often partial or complete resorption of the graft with replacement by fibrous tissue, resorption of endocortical bone and instability of the femoral prosthesis. Supplementation of allograft with OP-1 promotes initial graft resorption, thus hastening bone graft incorporation and remodelling but one case of stem subsidence, that may have been associated with early resorption seen in the OP-1 group, reinforces the need for further studies examining dose response. There was excellent incorporation of the allograft and HA, with new woven bone directly apposing the HA surface and integrated into the larger porous spaces of the HA. There was no adverse response to the HA and there was minimal to no subsidence of the stem at the cement-bone interface, as determined by RSA. Conclusion: This model is extremely valuable for investigating new biological approaches to reconstruction of major bone deficiency at revision hip replacement and demonstrates clear differences between materials used to supplement allograft, with HA and OP-1 giving encouraging results. RSA is an essential outcomes tool for this model