In vitro and in vivo dissolution of biocompatible S59 glass scaffolds.

Fabrication of porous tissue-engineering scaffolds from bioactive glasses (BAG) is complicated by the tendency of BAG compositions to crystallize in thermal treatments during scaffold manufacture. Here, experimental biocompatible glass S59 (SiO2 59.7 wt%, Na2O 25.5 wt%, CaO 11.0 wt%, P2O5 2.5 wt%, B2O3 1.3 wt%), known to be resistant to crystallization, was used in sintering of glass granules (300-500 µm) into porous scaffolds. The dissolution behavior of the scaffolds was then studied in vivo in rabbit femurs and under continuous flow conditions in vitro (14 days in vitro/56 days in vivo). The scaffolds were osteoconductive in vivo, as bone could grow into the scaffold structure. Still, the scaffolds could not induce sufficiently rapid bone ingrowth to replace the strength lost due to dissolution. The scaffolds lost their structure and strength as the scaffold necks dissolved. In vitro, S59 dissolved congruently throughout the 14-day experiments, resulting in only a slight reaction layer formation. Manufacturing BAG scaffolds from S59 that retain their amorphous structure was thus possible. The relatively rapid and stable dissolution of the scaffold implies that the glass S59 may have the potential to be used in composite implants providing initial strength and stable, predictable release of ions over longer exposure times.

Influence of polylactide coating stereochemistry on mechanical and in vitro degradation properties of porous bioactive glass scaffolds for bone regeneration.

The mechanical properties of polylactide stereocomplexes (PLA SC) have been primarily studied through tensile testing, with inconsistent results, and the compressive properties of PLA SC compared to homocrystalline or amorphous PLA remain poorly understood. In this study, we coated porous bioactive glass 13-93 scaffolds with amorphous, homocrystalline, or stereocomplex PLA to investigate their mechanical and degradation properties before and after immersion in simulated body fluid. The glass scaffolds had interconnected pores and an average porosity of 76%. The PLA coatings, which were 10-100 µm thick and approximately 3% of the glass scaffold mass, covered the glass to a large extent. The compressive strength and toughness of all PLA-coated scaffolds were significantly higher than those of uncoated scaffolds, with approximately a fourfold increase before immersion and a twofold increase after immersion. The compressive strength and toughness of PLA SC-coated scaffolds were similar to those of scaffolds with homocrystalline PLA coating, and significantly higher than for scaffolds with amorphous PLA coating. All PLA coatings moderated the initial pH increase caused by the glass, which could benefit surrounding cells and bone tissue in vivo after implantation.

Dissolution of Amorphous S53P4 Glass Scaffolds in Dynamic In Vitro Conditions.

The silicate-based bioactive glass S53P4 is clinically used in bone regenerative applications in granule form. However, utilization of the glass in scaffold form has been limited by the high tendency of the glass to crystallize during sintering. Here, careful optimization of sintering parameters enabled the manufacture of porous amorphous S53P4 scaffolds with a strength high enough for surgical procedures in bone applications (5 MPa). Sintering was conducted in a laboratory furnace for times ranging from 25 to 300 min at 630 °C, i.e., narrowly below the commencement of the crystallization. The phase composition of the scaffolds was verified with XRD, and the ion release was tested in vitro and compared with granules in continuous flow of Tris buffer and simulated body fluid (SBF). The amorphous, porous S53P4 scaffolds present the possibility of using the glass composition in a wider range of applications.

Biological response to an experimental implant for tibial tuberosity advancement in dogs: A pre-clinical study.

In this study, we propose a novel bioresorbable bioactive implant for tibial tuberosity advancement (TTA). The implant consists of a gradually resorbing load-bearing shell which encompasses rapidly resorbing small casings loaded with silica-based bioactive glass (BG) particulates which promote bone formation and reduce the risk of infection. The shell and the casings are manufactured by 3D printing from two medical grade bioresorbable polymers (a polyglycolide/lactide based and a polydioxanone based) that have different degradation rates. The casings are expected to resorb within days after surgery to expose the BG particulates while the shell would retain the load-bearing properties of the implant for the time required by bone healing. Unlike the currently used metallic devices, the novel implant is resorbed and excreted from the body once its purpose is fulfilled. This study presents a logical progression from the in vitro characterisation of the materials and implants to the in vivo investigation of the experimental implants. This included mechanical testing of the materials, finite element analysis of a preliminary design of the novel TTA implant, assessment of the degradation behaviour of the polymers and the ion exchange of BG in simulated body fluid, and investigation of the biological response to the novel implants after implantation in rabbits. The osteointegration of the novel implants was comparable to the osteointegration of Ti6Al4V implants in the control group; the biological efficacy and safety were confirmed. The biological response was in line with the expectations. The proof of concept for the novel TTA implants was demonstrated.

Gas-foamed poly(lactide-co-glycolide) and poly(lactide-co-glycolide) with bioactive glass fibres demonstrate insufficient bone repair in lapine osteochondral defects.

Deep osteochondral defects may leave voids in the subchondral bone, increasing the risk of joint structure collapse. To ensure a stable foundation for the cartilage repair, bone grafts can be used for filling these defects. Poly(lactide-co-glycolide) (PLGA) is a biodegradable material that improves bone healing and supports bone matrix deposition. We compared the reparative capacity of two investigative macroporous PLGA-based biomaterials with two commercially available bone graft substitutes in the bony part of an intra-articular bone defect created in the lapine femur. New Zealand white rabbits (n = 40) were randomized into five groups. The defects, 4 mm in diameter and 8 mm deep, were filled with neat PLGA; a composite material combining PLGA and bioactive glass fibres (PLGA-BGf); commercial beta-tricalcium phosphate (ß-TCP) granules; or commercial bioactive glass (BG) granules. The fifth group was left untreated for spontaneous repair. After three months, the repair tissue was evaluated with X-ray microtomography and histology. Relative values comparing the operated knee with its contralateral control were calculated. The relative bone volume fraction (∆BV/TV) was largest in the ß-TCP group (p ≤ 0.012), which also showed the most abundant osteoid. BG resulted in improved bone formation, whereas defects in the PLGA-BGf group were filled with fibrous tissue. Repair with PLGA did not differ from spontaneous repair. The PLGA, PLGA-BGf, and spontaneous groups showed thicker and sparser trabeculae than the commercial controls. We conclude that bone repair with ß-TCP and BG granules was satisfactory, whereas the investigational PLGA-based materials were only as good as or worse than spontaneous repair.

Bone morphogenic protein expression and bone formation are induced by bioactive glass S53P4 scaffolds in vivo.

The two-stage induced-membrane (IM) technique is increasingly used for treatment of large bone defects. In stage one, the bone defect is filled with polymethylmethacrylate (PMMA), which induces a membrane around the implant. In stage two, PMMA is replaced with bone graft. Bioactive glasses (BAGs) are bone substitutes with bone-stimulating and angiogenic properties. We have previously shown that a certain type of BAG can also induce a foreign-body membrane similar to PMMA. The aim of this study was to evaluate the bone-forming capacity of sintered BAG-S53P4 and poly(lactide-co-glycolide) (PLGA)-coated BAG-S53P4 scaffolds for potential use as bone substitutes in a single-stage IM technique. Sintered porous rods of BAG-S53P4, BAG-S53P4-PLGA, or PMMA were implanted in rabbit femurs for 2, 4, or 8 weeks. The expression of bone morphogenic protein (BMP)-2, -4, and -7 in the IMs of implanted materials were analyzed with real-time quantitative polymerase chain reaction. Micro-computed tomography imaging was used to evaluate bone growth and further verified with scanning electron microscopy. BAG-S53P4 and BAG-S53P4-PGLA scaffold IMs show similar or superior expression of BMP-2, -4, and -7 compared with PMMA IM. Bone ingrowth into BAG scaffolds increased over time. Active bone formation occurred inside the BAG scaffolds and the respective BMP expressions were similar or superior for the BAG IMs compared with PMMA, thus making BAGs a promising device for single-stage treatment of bone defects. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res B Part B: Appl Biomater, 2018. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 847-857, 2019.

Novel biorenewable composite of wood polysaccharide and polylactic acid for three dimensional printing.

Hemicelluloses, the second most abundant polysaccharide right after cellulose, are in practice still treated as a side-stream in biomass processing industries. In the present study, we report an approach to use a wood-derived and side-stream biopolymer, spruce wood hemicellulose (galactoglucomannan, GGM) to partially replace the synthetic PLA as feedstock material in 3D printing. A solvent blending approach was developed to ensure the even distribution of the formed binary biocomposites. The blends of hemicellulose and PLA with varied ratio up to 25% of hemicellulose were extruded into filaments by hot melt extrusion. 3D scaffold prototypes were successfully printed from the composite filaments by fused deposition modeling 3D printing. Combining with 3D printing technique, the biocompatible and biodegradable feature of spruce wood hemicellulose into the composite scaffolds would potentially boost this new composite material in various biomedical applications such as tissue engineering and drug-eluting scaffolds.

Improved dimensional stability with bioactive glass fibre skeleton in poly(lactide-co-glycolide) porous scaffolds for tissue engineering.

Bone tissue engineering requires highly porous three-dimensional (3D) scaffolds with preferable osteoconductive properties, controlled degradation, and good dimensional stability. In this study, highly porous 3D poly(d,l-lactide-co-glycolide) (PLGA) - bioactive glass (BG) composites (PLGA/BG) were manufactured by combining highly porous 3D fibrous BG mesh skeleton with porous PLGA in a freeze-drying process. The 3D structure of the scaffolds was investigated as well as in vitro hydrolytic degradation for 10weeks. The effect of BG on the dimensional stability, scaffold composition, pore structure, and degradation behaviour of the scaffolds was evaluated. The composites showed superior pore structure as the BG fibres inhibited shrinkage of the scaffolds. The BG was also shown to buffer the acidic degradation products of PLGA. These results demonstrate the potential of these PLGA/BG composites for bone tissue engineering, but the ability of this kind of PLGA/BG composites to promote bone regeneration will be studied in forthcoming in vivo studies.