As arthroplasty demand grows worldwide, the need for a novel cost-effective treatment option for articular cartilage (AC) defects tailored to individual patients has never been greater. 3D bioprinting can deposit patient cells and other biomaterials in user-defined patterns to build tissue constructs from the “bottom-up,” potentially offering a new treatment for AC defects. The aim of this research was to create bioinks that can be injected or 3D bioprinted to aid osteochondral defect repair using human cells. Novel composite bioinks were created by mixing different ratios of methacrylated alginate (AlgMA) with methacrylated gelatin (GelMA). Chondrocytes or mesenchymal stem cells (MSCs) were then encapsulated in the bioinks and 3D bioprinted using a custom-built extrusion bioprinter. UV and double-ionic (BaCl2 and CaCl2) crosslinking was deployed following bioprinting to strengthen bioink stability in culture. Chondrocyte and MSC spheroids were also produced via 3D culture and then bioprinted to accelerate cell growth and development of ECM in bioprinted constructs. Excellent viability of chondrocytes and MSCs was seen following bioprinting (>95%) and maintained in culture over 28 days, with accelerated cell growth seen with inclusion of MSC or chondrocyte spheroids in bioinks (p<0.05). Bioprinted 10mm diameter constructs maintained shape in culture over 28 days, whilst construct degradation rates and mechanical properties were improved with addition of AlgMA (p<0.05). Composite bioinks were also injected into in vitro osteochondral defects (OCDs) and crosslinked in situ, with maintained cell viability and repair of osteochondral defects seen over a 14-day period. In conclusion we developed novel composite AlgMA/GelMA bioinks that can be triple-crosslinked, facilitating dense chondrocyte and MSC growth in constructs following 3D bioprinting. The bioink can be injected or 3D bioprinted to successfully repair in vitro OCDs, offering hope for a new approach to treating AC defects

As arthroplasty demand grows worldwide, the need for a novel cost-effective treatment option for articular cartilage (AC) defects tailored to individual patients has never been greater. 3D bioprinting can deposit patient cells and other biomaterials in user-defined patterns to build tissue constructs from the “bottom-up,” potentially offering a new treatment for AC defects. The aim of this research was to create bioinks that can be injected or 3D bioprinted to aid osteochondral defect repair using human cells. Novel composite bioinks were created by mixing different ratios of methacrylated alginate (AlgMA) with methacrylated gelatin (GelMA). Chondrocytes or mesenchymal stem cells (MSCs) were then encapsulated in the bioinks and 3D bioprinted using a custom-built extrusion bioprinter. UV and double-ionic (BaCl2 and CaCl2) crosslinking was deployed following bioprinting to strengthen bioink stability in culture. Chondrocyte and MSC spheroids were also bioprinted to accelerate cell growth and development of ECM in bioprinted constructs. Excellent viability of chondrocytes and MSCs was seen following bioprinting (>95%) and maintained in culture over 28 days, with accelerated cell growth seen with inclusion of MSC or chondrocyte spheroids in bioinks (p<0.05). Bioprinted 10mm diameter constructs maintained shape in culture over 28 days, whilst construct degradation rates and mechanical properties were improved with addition of AlgMA (p<0.05). Composite bioinks were also injected into in vitro osteochondral defects (OCDs) and crosslinked in situ, with maintained cell viability and repair of osteochondral defects seen over a 14-day period. In conclusion we developed novel composite AlgMA/GelMA bioinks that can be triple-crosslinked, facilitating dense chondrocyte and MSC growth in constructs following 3D bioprinting. The bioink can be injected or 3D bioprinted to successfully repair in vitro OCDs, offering hope for a new approach to treating AC defects

As arthroplasty demand grows worldwide, the need for a novel cost-effective treatment option for articular cartilage (AC) defects tailored to individual patients has never been greater. 3D bioprinting can deposit patient cells and other biomaterials in user-defined patterns to build tissue constructs from the “bottom-up,” potentially offering a new treatment for AC defects. Novel composite bioinks were created by mixing different ratios of methacrylated alginate (AlgMA) with methacrylated gelatin (GelMA) and collagen. Chondrocytes and mesenchymal stem cells (MSCs) were then encapsulated in the bioinks and 3D bioprinted using a custom-built extrusion bioprinter. UV and double-ionic (BaCl2 and CaCl2) crosslinking was deployed following bioprinting to strengthen bioink stability in culture. Chondrocyte and MSC spheroids were also bioprinted to accelerate cell growth and development of ECM in bioprinted constructs. Excellent viability of chondrocytes and MSCs was seen following bioprinting (>95%) and maintained in culture, with accelerated cell growth seen with inclusion of cell spheroids in bioinks (p<0.05). Bioprinted 10mm diameter constructs maintained shape in culture over 28 days, whilst construct degradation rates and mechanical properties were improved with addition of AlgMA (p<0.05). Composite bioinks were also injected into in vitro osteochondral defects and crosslinked in situ, with maintained cell viability and repair of osteochondral defects seen over a 14-day period. In conclusion, we developed novel composite bioinks that can be triple-crosslinked, facilitating successful chondrocyte and MSC growth in 3D bioprinted scaffolds and in vitro repair of an osteochondral defect model. This offers hope for a new approach to treating AC defects

Abstract. INTRODUCTION. Polyetheretherketone (PEEK) is a high-performance thermoplastic polymer which has found increasing application in orthopaedic implant devices and has a lot of promise for ‘made-to-measure’ implants produced through additive manufacturing [1]. However, a key limitation of PEEK is that it is bioinert and there is a requirement to functionalise its surface to make the material osteoconductive to ensure a more rapid, improved and stable fixation, in vivo. One approach to solving this issue is to modify PEEK with bioactive materials, such as hydroxyapatite (HA). OBJECTIVE. To 3D PEEK/HA composite materials using a Fused Filament Fabrication (FFF) approach to enhance the properties of the PEEK matrix. METHODS. PEEK/HA composites (0–30% w/w HA/PEEK) were 3D printed using a modified Ultimaker 2+ 3D printer. The mechanical, thermal, physical, chemical and in vitro properties of the 3D printed samples were all studied as part of this work. RESULTS. The CT images of both the filament and the 3D printed samples showed that the HA material was evenly dispersed throughout the bulk all the samples. SEM/EDX measurements highlighted that HA was homogenously distributed across the surface. As the HA content of the samples increases, so does the tensile modulus, ranging from 4.2 GPa (PEEK) to 6.1 GPa (30% HA/PEEK) and are significantly higher than datasheet information of injected molded PEEK samples. All materials supported the growth of osteoblast cells on their surface. CONCLUSIONS. The results clearly show that we can successfully and easily 3D print HA/PEEK composite materials up to 30% w/w HA/PEEK. The samples produced have a homogeneous distribution of HA in both the bulk and surface of all the samples, and their mechanical performance of the PEEK is enhanced by the addition of HA

To prevent the reported side effects of rhBMP-2, an important cytokine with bone forming capacity, the sustained release of rhBMP-2 is highly important. Synthetic copolymer polylactic acid-polyethylene glycol (PLA-PEG) is already shown to be a good carrier for rhBMP-2. The nano-sized hydroxyapatite (nHAp) is mentioned to be superior to conventional hydroxyapatite due to its decreased particle size which increases the surface area, so protein-cell adhesion and mechanical properties concomitantly. In the literature no study is reported with PLA-PEG / rhBMP-2/ nHAp for bone regeneration. In this study, we assessed the controlled release profile of rhBMP-2 from the novel biomaterial of PLA-PEG / rhBMP-2 / nHAp in vitro and evaluated the bone forming capacity of the composite in rat posterolateral spinal fusion (PSF) model in vivo. Composites were prepared via addition of rhBMP-2 (0µg, 3µg or 10µg) and nHAp (12.5mg) into PLA-PEG (5mg) + acetone solution and shaping. The release kinetics of the cytokine from the composites with 5µg BMP-2 was investigated by ELISA. The effect of nHAp and nHAp with rhBMP-2 on cell differentiation (rat BMSC cells, passage 3) was tested with ALP staining. In vivo bone formation was investigated by PSF on L4-L5 in a total of 36 male SD rats and weekly µCT results and histology at 8. th. weeks post operation were used for assessment of the bone formation. All animal experiments was approved by the institutional review board confirming to the laws and regulations of Japan. The composite showed an initial burst release in the first 24 hours (51.7% of the total released rhBMP-2), but the release was continued for the following 21 days. Thus, the sustained release of rhBMP-2 from the composite was verified. ALP staining results showed nHAp with rhBMP-2 contributed better on differentiation than nHAp itself. µCT and histology demonstrated that spinal fusion was achieved either one or both transverse processes in almost all BMP 3µg and BMP 10µg treated animals. On the contrary, only small or no bone formation was observed in the BMP0µg group (bilateral non-union / unilateral fusion/ bilateral fusion, BMP0µg group; 9/0/0, BMP3µg group; 1/0/11, BMP10µg group; 0/1/11). We developed a new technology for bone regeneration with BMP-2/PLA-PEG/nHAp composite. With this composite, the required dose of BMP-2 for spinal fusion in rats (10µg) was decreased to 1/3 (3µg) which can be explained by the superior properties of nano-sized hydroxyapatite and by the achievement of sustainable release of rhBMP-2 from the composite. This study is supported by Japanese Society of the Promotion of Science (JSPS) and Scientific and Technological Research Council of Turkey (TUBITAK). [Project No: 215S834]

Objective. In the present study, we aimed to assess whether gelatin/β-tricalcium phosphate (β-TCP) composite porous scaffolds could be used as a local controlled release system for vancomycin. We also investigated the efficiency of the scaffolds in eliminating infections and repairing osteomyelitis defects in rabbits. Methods. The gelatin scaffolds containing differing amounts of of β-TCP (0%, 10%, 30% and 50%) were prepared for controlled release of vancomycin and were labelled G-TCP0, G-TCP1, G-TCP3 and G-TCP5, respectively. The Kirby-Bauer method was used to examine the release profile. Chronic osteomyelitis models of rabbits were established. After thorough debridement, the osteomyelitis defects were implanted with the scaffolds. Radiographs and histological examinations were carried out to investigate the efficiency of eliminating infections and repairing bone defects. Results. The prepared gelatin/β-TCP scaffolds exhibited a homogeneously interconnected 3D porous structure. The G-TCP0 scaffold exhibited the longest duration of vancomycin release with a release duration of eight weeks. With the increase of β-TCP contents, the release duration of the β-TCP-containing composite scaffolds was decreased. The complete release of vancomycin from the G-TCP5 scaffold was achieved within three weeks. In the treatment of osteomyelitis defects in rabbits, the G-TCP3 scaffold showed the most efficacious performance in eliminating infections and repairing bone defects. Conclusions. The composite scaffolds could achieve local therapeutic drug levels over an extended duration. The G-TCP3 scaffold possessed the optimal porosity, interconnection and controlled release performance. Therefore, this scaffold could potentially be used in the treatment of chronic osteomyelitis defects. Cite this article: J. Zhou, X. G. Zhou, J. W. Wang, H. Zhou, J. Dong. Treatment of osteomyelitis defects by a vancomycin-loaded gelatin/β-tricalcium phosphate composite scaffold. Bone Joint Res 2018;7:46–57. DOI: 10.1302/2046-3758.71.BJR-2017-0129.R2

Critical-sized bone defects remain challenging in the clinical setting. Autologous bone grafting remains preferred by clinicians. However, the use of autologous tissue is associated with donor-site morbidity and limited accessibility to the graft tissue. Advances in the development of synthetic bone substitutes focus on improving their osteoinductive properties. Whereas osteoinductivity has been demonstrated with ceramics, it is still a challenge in case of polymeric composites. One of the approaches to improve the regenerative properties of biomaterials, without changing their synthetic character, is the addition of inorganic ions with known osteogenic and angiogenic properties. We have previously reported that the use of a bioactive composite with high ceramic content composed of poly(ethyleneoxide terephthalate)/poly(butylene terephthalate) (1000PEOT70PBT30, PolyActive, PA) and 50% beta-tricalcium phosphate (β-TCP) with the addition of zinc in a form of a coating of the TCP particles can enhance the osteogenic differentiation of human mesenchymal stromal cells (hMSCs) (3). To further support the regenerative properties of these scaffolds, inorganic ions with known angiogenic properties, copper or cobalt, were added to the coating solution. β-TCP particles were immersed in a zinc and copper or zinc and cobalt solution with a concentration of 15 or 45 mM. 3D porous scaffolds composed of 1000PEOT70PBT30 and pure or coated β-TCP were additively manufactured by 3D fibre deposition. The osteogenic and angiogenic properties of the fabricated scaffolds were tested in vitro through culture with hMSCs and human umbilical vein endothelial cells, respectively. The materials were further evaluated through ectopic implantation in an in vivo mini-pig model. The early expression of relevant osteogenic gene markers (collagen-1, osteocalcin) of hMSCs was upregulated in the presence of lower concentration of inorganic ions. Further analysis will focus on the evaluation of ectopic bone formation and vascularisation of these scaffolds after implantation in a mini-pig ectopic intramuscular model

Objectives. The purpose of this study was to evaluate in vivo biocompatibility of novel single-walled carbon nanotubes (SWCNT)/poly(lactic-co-glycolic acid) (PLAGA) composites for applications in bone and tissue regeneration. Methods. A total of 60 Sprague-Dawley rats (125 g to 149 g) were implanted subcutaneously with SWCNT/PLAGA composites (10 mg SWCNT and 1gm PLAGA 12 mm diameter two-dimensional disks), and at two, four, eight and 12 weeks post-implantation were compared with control (Sham) and PLAGA (five rats per group/point in time). Rats were observed for signs of morbidity, overt toxicity, weight gain and food consumption, while haematology, urinalysis and histopathology were completed when the animals were killed. Results. No mortality and clinical signs were observed. All groups showed consistent weight gain, and the rate of gain for each group was similar. All groups exhibited a similar pattern for food consumption. No difference in urinalysis, haematology, and absolute and relative organ weight was observed. A mild to moderate increase in the summary toxicity (sumtox) score was observed for PLAGA and SWCNT/PLAGA implanted animals, whereas the control animals did not show any response. Both PLAGA and SWCNT/PLAGA showed a significantly higher sumtox score compared with the control group at all time intervals. However, there was no significant difference between PLAGA and SWCNT/PLAGA groups. Conclusions. Our results demonstrate that SWCNT/PLAGA composites exhibited in vivo biocompatibility similar to the Food and Drug Administration approved biocompatible polymer, PLAGA, over a period of 12 weeks. These results showed potential of SWCNT/PLAGA composites for bone regeneration as the low percentage of SWCNT did not elicit a localised or general overt toxicity. Following the 12-week exposure, the material was considered to have an acceptable biocompatibility to warrant further long-term and more invasive in vivo studies. Cite this article: Bone Joint Res 2015;4:70–7

Medical grade polyurethanes have been widely promoted for biomedical applications. In particular, the use of polycarbonate-urethanes (PCU) has drawn considerable attention in the orthopaedic device industry as a result of their excellent mechanical properties, biostability and biocompatibility. PCUs have been extensively utilized in vascular grafts, stents and artificial heart valves. Specifically, bionate thermoplastic PCU, commercially produced by DSM PTG (Berkeley, California), has been of great interest in the field of orthopaedics because of its outstanding load-bearing properties and excellent wear resistance. Also, it is characterized by its long-term durability and resistance to hydrolytic degradation making it a good candidate for in-vivo orthopaedic applications. PCUs have been considered for meniscal replacement because of its unique weight-bearing capabilities, ability to withstand intense forces within the knee joint and ease of lubrication due to its hydrophilic nature. In addition, the low frictional properties essential for a meniscal replacement is obtainable with PCUs. Materials used for this study were a commercial polycarbonate-urethanes, Bionate PCU 80A (B8) and 90A (B9) pellets, and polyethylene continuous strands fibres (PE) obtained from DSM Polymer Technology Group, USA. Some quantity of the B8 and B9 pellets were dried separately in a vacuum oven at 100°C for 14 hours. A custom mould was designed for the production of the mechanical test samples. The quantity of the constituent materials was determined using composite theory known as the Rule of Mixtures. E. c. =. E. m. V. m. +. E. f. E. f. where V. m. and V. f. are the volume fraction of the matrix and fibre respectively. Three specimens each of the prepared composites were tested for tensile and compression strength and at a crosshead speed of 12 mm/min using a Zwick/Roell 1484 Material Testing Machine. The PCUs were not as stiff as their fibre-reinforced composites, which indicate that the stiffness of the PCU composite materials is a function of both the stiffness of the PCU matrix and the interspersed fibres. The tensile moduli of composites of B8 and B9 increased appreciably with PE. An increase of 227% was obtained for the B8 with the incorporation of PE fibres while percentage increase in stiffness for B9 was 148% for PE reinforcement fibres. The compressive modulus dropped with the inclusion of the PE fibres in the B9, a reduction of 55% was recorded while an increment of 4% was obtained with PE added to the B8. The results from this study demonstrate that the tensile and compressive properties of PCU can be custom-tailored to that of the meniscal tissue by systematically embedding reinforcement fibres into the PCU matrix such that a composite with desirable mechanical properties is obtained. The results of both tensile and compressive results visibly revealed the reinforcing effect of the fibres used in this study. However, additional studies are required to completely describe the PCU composite as a candidate meniscal substitute capable of gaining its full functionality

Calcium phosphate ceramics and bioactive glasses are frequently used in orthopedic surgery to stimulate the regeneration of bone tissue due to their superior compatibility to bone tissue. Nevertheless, the brittleness and lack of self-healing behavior of bioceramics are still considered as serious drawbacks. Therefore, these bioceramics have been combined with organic biomaterials for several decades. Since the 1990s, the emergence of nanotechnology has accelerated the progress with respect to the development of organic-inorganic nanocomposites of improved functionality compared to conventional composite biomaterials. This presentation focuses on the development of injectable (nano)composites with self-healing and/or load-bearing capacity. To this end, the affinity between polymeric and inorganic components was tuned by modifying non-covalent interactions between both composite components. Specifically, we exploited reversible interactions between hydrogel matrices and inorganic nanoparticles (traditional nanocomposites), hydrogel nanoparticles and inorganic nanoparticles (colloidal nanocomposites), as well as fibers and bioceramic matrices (fiber-reinforced cement composites). The resulting composite biomaterials were mechanically strong and self-healing, which may open up new avenues of research on the applicability of self-healing and load-bearing composite biomaterials for regenerative medicine

Aims. The efficacy of saline irrigation for treatment of implant-associated infections is limited in the presence of porous metallic implants. This study evaluated the therapeutic efficacy of antibiotic doped bioceramic (vancomycin/tobramycin-doped polyvinyl alcohol composite (PVA-VAN/TOB-P)) after saline wash in a mouse infection model implanted with titanium cylinders. Methods. Air pouches created in female BalBc mice by subcutaneous injection of air. In the first of two independent studies, pouches were implanted with titanium cylinders (400, 700, and 100 µm pore sizes) and inoculated with Staphylococcus aureus (1 × 10. 3. or 1 × 10. 6. colony-forming units (CFU)/pouch) to establish infection and biofilm formation. Mice were killed after one week for microbiological analysis. In the second study, pouches were implanted with 400 µm titanium cylinders and inoculated with S. aureus (1 × 10. 3. or 1 × 10. 6. CFU/pouch). Four groups were tested: 1) no bacteria; 2) bacteria without saline wash; 3) saline wash only; and 4) saline wash plus PVA-VAN/TOB-P. After seven days, the pouches were opened and washed with saline alone, or had an additional injection of PVA-VAN/TOB-P. Mice were killed 14 days after pouch wash. Results. The first part of the study showed that low-grade infection was more significant in 400 µm cylinders than cylinders with larger pore sizes (p < 0.05). The second part of the study showed that saline wash alone was ineffective in eradicating both low- and high-grade infections. Saline plus PVA-VAN/TOB-P eradicated the titanium cylinder-associated infections, as manifested by negative cultures of the washouts and supported by scanning electron microscopy and histology. Conclusion. Porous titanium cylinders were vulnerable to bacterial infection and biofilm formation that could not be treated by saline irrigation alone. Application of PVA-VAN/TOB-P directly into the surgical site alone or after saline wash represents a feasible approach for prevention and/or treatment of porous implant-related infections. Cite this article: Bone Joint Res 2024;13(11):622–631

Aims: Both partial and total functional disorders of spine are one of the most disabling, common and costly problem of current surgery. The surgical treatment may involve the partial or total resection of the Intervertebral Disc (IVD). Thus, implants for vertebral fusion are often required in order to immobilize the diseased column. Cage implants are designed in order to separate contiguous vertebrae allowing an adequate stress transfer and favoring bone growth. In this paper the biomechanical and histological properties of novel composite cages and commercial titanium implants have been in vitro and in vivo investigated. Materials: Novel composite lumbar cages were designed by F.E.M., manufactured and implanted in porcine spine at the L4-L5 lumbar zone of five pigs (large white-duroc race of 50–55 Kg by weight and 1.9–2.1 months old). Each composite cage was prepared by filament winding technology by using PEI (PolyEtherImmide – GE Polymerland ULTEM 1000/1000) as matrix and Carbon fibre (Torayca T400-B 6000-50B) as reinforcement with a winding angle of 45A1 degree. Mechanical properties were investigated according to ASTM standard on composite material, novel composite cage, titanium cage and the natural disc. The device was coated with PEI – HA (hydroxyapatite) solution in order to improve the bone interaction. The behaviour of the composite cage was compared to titanium lumbar cages (SOFAMOR Danek) through biomechanical and histological tests. Results: Tensile test performed on composite material have showed a Young’s Modulus equal to 40,1 GPa, maximum tensile strength equal to 602 MPa. Compressive test on the composite cage showed an Elastic Modulus value of 22 GPa. The comparison among the three systems displayed comparable compliance for titanium (0,0014mm/mm) and composite cage (0,0031mm/mm) while an higher compliance in the case of natural disc (0,0521mm/mm). All pigs showed good health up to the sacrificing date. Particularly, histological tests after two months from the implantation already showed abundant the presence of new-formed tissue around the composite cage. Conclusions:. The results demonstrate that PEI reinforced with Carbon fibres composite cages coated with HA show excellent performance. Mechanical properties of the composite cages are closer to the properties of cortical bone than those of titanium cages, thus reducing the effect of stress concentration and stress shielding and as observed for stiff metal implants

Introduction. Support of appositional bone ingrowth and resistance to bacterial adhesion and biofilm formation are preferred properties for biomaterials used in spinal fusion surgery. Although polyetheretherketone (PEEK) is a widely used interbody spacer material, it exhibits poor osteoconductive and bacteriostatic properties. In contrast, monolithic silicon nitride (Si. 3. N. 4. ) has shown enhanced osteogenic and antimicrobial behavior. Therefore, it was hypothesized that incorporation of Si. 3. N. 4. into a PEEK matrix might improve upon PEEK's inherently poor ability to bond with bone and also impart resistance to biofilm formation. Methods. A PEEK polymer was melted and compounded with three different silicon nitride powders at 15% (by volume, vol.%), including: (i) α-Si. 3. N. 4. ; (ii) a liquid phase sintered (LPS) ß-Si. 3. N. 4. ; and (iii) a melt-derived SiYAlON mixture. These three ceramic powders exhibited different solubilities, polymorphic structures, and/or chemical compositions. Osteoconductivity was assessed by seeding specimens with 5 × 10. 5. /ml of SaOS-2 osteosarcoma cells within an osteogenic media for 7 days. Antibacterial behavior was determined by inoculating samples with 1 × 10. 7. CFU/ml of Staphylococcus epidermidis (S. epi.) in a 1 × 10. 8. /ml brain heart infusion (BHI) agar culture for 24 h. After staining with PureBlu™ Hoechst 33342 or with DAPI and CFDA for SaOS-2 cell adhesion or bacterial presence, respectively, samples were examined with a confocal fluorescence microscope using a 488 nm Krypton/Argon laser source. Images were also acquired using a FEG-SEM in secondary and backscattered modes on gold sputter-coated specimens (∼20–30Å). Hydroxyapatite (HAp) deposition was measured using a laser microscope. Raman spectra were collected for samples in backscattering mode using a triple monochromator using a 532 nm excitation source (Nd:YVO. 4. diode-pumped solid-state laser). Results. PEEK composites with 15 vol.% α-Si. 3. N. 4. , LPS ß-Si. 3. N. 4. , or the SiYAlON mixture showed significantly greater SaOS-2 cell proliferation (>600%, p<0.003, cf., Fig. 1(a)) and HAp deposition (>100%, p<0.003, cf., Fig. 1(b)) relative to monolithic PEEK. The largest increase in cell proliferation was observed with the SiYAlON composite, while the greatest amount of HAp was found on the LPS ß-Si. 3. N. 4. composite. Following exposure to S. epidermidis, the composite containing the LPS β-Si. 3. N. 4. powder showed one order of magnitude reduction in adherent live bacteria (p<0.003, cf., Fig. 1(c)) as compared to the PEEK monolith. It is interesting to note that the composite containing α-Si. 3. N. 4. exhibited the worst bacterial resistance (i.e., ∼100% higher than monolithic PEEK), suggesting that the bacteriostatic effectiveness of Si. 3. N. 4. bioceramics is apparently dependent upon the presence of selective sintering additives, viz. yttria and alumina. Conclusions. The addition of 15 wt.% of specific Si. 3. N. 4. powders to PEEK showed enhanced SaOS-2 cell adhesion, proliferation, and HAp deposition when compared to monolithic PEEK. These same composites also showed resistance to S. epi. adhesion and biofilm formation.. Although improvements in osteoconductivity have been previously observed by compounding or coating PEEK with HAp, titanium, or tantalum, these approaches did not provide anti-microbial properties. Compounding PEEK with Si. 3. N. 4. represents a significant advancement due to its ability to provide both improved bone apposition and resistance to biofilm formation. For any figures or tables, please contact the authors directly

Sustained release of BMP-2 is reported to be able to reduce the required dose of BMP-2 for bone induction. Nanohydroxyapatite (nHAp) has an osteoinduction capability which is lack in conventional hydroxyapatite. In this study, we combined PLA-PEG with nHAp and investigated the bone regenerative capacity of the newly established composite material of rhBMP-2/PLA-PEG/nHAp in a rat model of spinal fusion. The PLA-PEG was liquidized in acetone and mixed with nHAp and rhBMP-2. The sheet-shaped BMP-2/PLA-PEG (5mg)/nHAp (12.5mg) composites were prepared while evaporating the acetone. The release kinetics of rhBMP-2 from the composite was investigated by ELISA. In vivo bone formation was investigated by posterolateral spinal fusion in rats (the dosage of rhBMP-2; 0µg/ 0.5µg / 3µg). Bone formation was assessed by µCT and histology at post-op. 8 weeks. The composite showed the burst-release in the initial 24 hours (69% of total release) and the subsequent sustained-release for 25 days. According to µCT and histology of the spinal fusion experiment for all groups the bone formation was observed. While no bony bridging was observed in 0 µg and 0.5 µg BMP groups; in 3 µg group bony bridging and fusion were achieved. We developed a new technology for bone regeneration with rhBMP-2/PLA-PEG/nHAp composite. The reduction in the required dose of BMP-2 for bone induction was achieved. This result can be explained by the high bone induction ability of nHAp and sustainable release of BMP from PLA-PEG in the composite

Abstract. Objectives. Direct ink writing (DIW) has gained considerable attention in production of personalized medical implants. Laponite nanoclay is added in polycaprolactone (PCL) to improve printability and bioactivity for bone implants. The 3D structure of DIW printed PCL/Laponite products was qualitatively evaluated using micro-CT. Methods. PCL/LP composite ink was formulated by dissolving 50% m/v PCL in dichloromethane with Laponite loading of up to 30%. The rheological properties of the inks were determined using Discovery HR-2 rheometer. A custom-made direct ink writer was used to fabricate both porous scaffold with 0°/90° lay-down pattern, and solid dumbbell-shaped specimens (ASTM D638 Type IV) with two printing orientations, 0° and 90° to the loading direction in tensile testing. The 3D structure of specimens was assessed using a micro-CT. Independent t-tests were performed with significance level at p<0.05. Results. The addition of Laponite in PCL ink has significantly enhanced viscosity for shape fidelity and shear-thinning property facilitating extrusion for DIW. Uniform distribution of Laponite was illustrated by micro-CT. For the 32-layer scaffold, interconnectivity of pores is observed at all 3 planes. The variation of height and width of layers is within 6% except the bottom 2 layers which are significantly lower and wider than other layers for mechanical support. For solid specimens, no ditches/interfaces between filaments are observed in 90° orientation while they are distinctive in 0° orientation because deposited filaments contact each other sooner in 90° orientation. 90° specimens also have lower air gap fraction (0.8 vs 5.4 %) and significantly higher Young's modulus (235 vs 195 MPa) and tensile strength (12.0 vs 9.5 MPa). Conclusions. The mechanical properties and printability of PCL/Laponite composites can be improved by controlling printing parameters; Micro-CT is an important tool to investigate the structure and properties of 3D printed products for bone tissue engineering

Vast amount of literature is available on mechanical properties of PMMA, but not about the composite specimens of old and new cement. This is important, as in cement revision has become established technique with good clinical results. Originally Greenwald and later Li described properties of such specimens. However in these studies the old samples were only few days old, unlike clinical situation, where the old cement is a few years old. We therefore decided to test short-term mechanical properties of composite specimens and compare these with new uniform specimens. We choose specimens of cement 3–17 years old (median 11.8) for the manufacturing of the composite specimens. Material and Methods: Uniform and composite specimens were fabricated and were tested for bending, tensile and shear strength. Beam shaped specimens were fabricated for bending and tensile tests, cylindrical for shear. Seventeen beams and eight cylindrical specimens fabricated earlier (1988–2002) using the same moulds were available to form composite specimens. Old specimens were placed into the moulds and new cement was injected next to these. Specimens were allowed to polymerize at room temperature for 30 minutes and stored in saline at 37 °C for 6 weeks before testing. Specimens were tested in Lloyds EZ 20 machine with customized jig so that the junction was subjected to bending, tensile or shear force. Results: Bending tests: The load and bending stress for new specimen was 80N and 47MPa as compared with 72N and 38MPa for composite specimens. 4 composite specimens failed though old cement, 3 through the junction and 1 through the new cement. There was no statistical difference in maximum load between uniform and composite specimens (p=.29). However there was a difference in the stress between uniform and composite specimens. Tensile tests: The load and tensile stress for new specimen was 916N and 29MPa as compared with 795N and 24MPa for composite specimens. 7 composites failed through old cement, 1 through new cement and 1 at junction. There was difference in the load and stress of uniform specimens as compared with composite specimens. Shear tests: The load and shear stress for new specimen was 2718N and 35MPa as compared with 2055N and 26MPa for composite specimens. There was significant difference in load as well as stress in uniform specimens as compared with composite specimens. Discussion: This study demonstrates that composite specimens fail at 89.6% of bending load, 77.2% of tensile and 74.6% of shear load as compared with uniform new cement specimens. They have 81.4% of bending stress, 74.9% of tensile stress and 73.3% of shear stress at failure as compared with uniform specimens. Of more importance is the fact that only four of these composite specimens (23.5%) failed at the junction and the rest thirteen failed either through old cement (64.7%) or through new cement (11.8%)

Introduction: Scant amount of information is available on mechanical properties of composite specimens of old and new cement. In previous studies evaluating this, old samples were only few days old, unlike clinical situation, where the old cement is a few years old. We evaluated short-term mechanical properties of composite specimens and compared these with new uniform specimens. Material and Methods: Uniform and composite specimens were fabricated and were tested for bending, tensile and shear strength. Seventeen beams and eight cylindrical specimens fabricated earlier (median age 11.8 years) using same moulds were available to form composite specimens. Specimens were stored in saline at 37 °C for 6 weeks before testing. Results: Bending tests: Load and bending stress for new specimen was 82.9N and 49.5MPa as compared with 74.3N and 40.3MPa for composite specimens. 4 composite specimens failed though old cement, 3 through junction and 1 through new cement. There was no statistical difference in maximum load (p, 0.3) or stress (P, 0.06) between uniform and composite specimens. Tensile tests: Load and tensile stress for new specimen was 941.5N and 29.5MPa as compared with 726.9N and 22.1MPa. There was difference in the load and stress of uniform specimens as compared with composite specimens. Shear tests: Load and shear stress for new specimen was 2692.9N and 34.5MPa as compared with 2009.9N and 25.3MPa. There was significant difference in load as well as stress in uniform specimens as compared with composite specimens. Discussion: This study demonstrates that composite specimens fail at 89.6% of bending load, 77.2% of tensile and 74.6% of shear load as compared with uniform new cement specimens. Of more importance is the fact that only four of these composite specimens (23.5%) failed at the junction and the rest thirteen failed either through old cement (64.7%) or through new cement (11.8%)

Introduction. In total hip arthroplasty ceramic on ceramic bearing couples are used more and more frequently and on a wordwide basis. The main reason of this choice is reduction of wear debris and osteolysis. The tribological properties and the mechanical behaviour of the implanted ceramic must remain the same throughout the patient's life. The aim of this study was to evaluate the resistance of Alumina Matrix Composite to environmental degradation. Material and method. The alumina matrix composite or BIOLOX ® delta is manufactured in Germany by CeramTec. It is made up of 80 vol.% Al2O3, 17 vol.% Yttria Stabilized ZrO2 and 3vol.% strontium aluminate platelets. The zirconia grains account for 1.3 mol.% of the Yttria content. Accelerated aging tests in water steam at 142°C, 134°C, 121°C, and 105°C were performed to evaluate the aging kinetics of the composite. X-ray diffraction was used to determine the monoclinic phase content on the material surface. Phase transformation is associated with weakness and increase in roughness of zirconia ceramic implants. Results. The data below shows average monoclinic contents before and after aging in water vapour according to the ISO standard test (134°C, 2 bars water steam, 10 h) on the surface and inside the 28 mm taper(12/14 taper) femoral ball heads manufactured in alumina ceramic composite. There are precisions concerning the roughness and the load to failure before and after aging concerning 28mm diameter heads. Before Aging 13%+/-3% of Monoclinic content. After 10 H at 134°C23%+/-3% of Monoclinic content the roughness of the polished surface remain the same (5nm+/− 2). The load to failure of 28 mm heads before aging is 76 kN +/− 5kN, and 72 kN +/− 5kN after aging. The results show that although a rise in monoclinic content is predictable after long aging duration in vivo, the impact of the transformation is quite different to monolithic zirconia. A zirconia femoral head exhibits an important increase of roughness from 2 nm to more than 50 nm when submitted to the same duration of ageing. Other tests with hip simulators under severe micro separation have been done to analyse the impact of aging on wear performance. The main wear zone on femoral heads underwent a phase transformation from tetragonal to monoclinic (23% monoclinic) at 5 milion cycles duration without any change in roughness after 5Mc duration. Conclusion. This experimental testing program has enabled a prediction for the long-term in vivo environmental resistance of prostheses made out of Alumina Matrix Composite. The substantial improvement in mechanical properties and the excellent wear behaviour, even under severe microseparation conditions has been clinically confirmed. Today more than 960,000 ceramic ball heads and more than 450 000 ceramic inserts made of the alumina matrix composite have been implanted. Additionally, due to enhanced mechanical behaviour, new applications in orthopaedics are possible

Aim. Treatment principles of chronic osteomyelitis include debridement, clean sampling, excision of dead bone, stabilization, dead space management, soft tissue closure and systemic antibiotic therapy. Dead space management becomes very complicated, if the bone infection is caused by multi-resistant bacteria. The aim of this investigation was to evaluate the effect of a new vancomycin-loaded hydroxyapatite / calcium sulfate composite. *. in the treatment of chronic osteomyelitis (OM) caused by multi-resistant bacteria. Method. From June 2015 to November 2015, 7 patients (4 males, 3 females, average age 52.6y) were treated according to the above mentioned principles using the new vancomycin-loaded hydroxyapatite / calcium sulfate composite. *. Infections were caused by methicillin-resistant Staphylococcus aureus (MRSA), multi-resistant Staphylococcus epidermidis (MRSE) and polymicrobial, vancomycin-sensitive bacteria. We used a two-stage protocol with debridement, excision of bone and external stabilization in the first stage, followed by bone defect reconstruction. To fill the residual bone defects, in 3 patients the new vancomycin-loaded hydroxyapatite / calcium sulfate composite. *. (10mL) was used on its own and in 4 patients combined with 18mL of an unloaded calcium sulfate / hydroxyapatite composite. **. Post-operative follow-up was evaluated clinically and by radiographs and CT scans at 6, 14 and 24 weeks. Results. In 6 of 7 patients rapid control of infection was achieved. Soft tissue reactions and prolonged white wound drainage (caused by calcium sulfate dissolution) was seen in 3 of 7 patients. In 6 of 7 patients recurrence of infection has not been observed so far. Radiographs showed different elution intervals of the radiocontrast agent (Iohexol), depending on anatomical location. Bone remodelling or replacement of the composite by new bone was not uniform in the patients and showed specific radiographic signs. In addition to the so-called „puddle sign“, we found septae, membranes, vacuoles and sometimes arc-like structures. Therefore, we suggest the name “arc-sign” for these formations. Conclusions. During the follow-up of the first 7 patients treated with the unloaded calcium sulfate / hydroxyapatite composite. **. in 6 of 7 cases no recurrence of infection was observed. This is very promising in the difficult situation of bone infections caused by multi-resistant bacteria. Follow-up radiographs and CT-scans showed specific patterns during the resorption of the composite and the formation of new bone, which have not been described in other bone graft substitutes so far. The bone defects are not completely filled yet, but the affected bones are clinically stable and patients can ambulate with full weight bearing

The aim of this study was to evaluate the trochlear bone and cartilaginous regeneration of rabbits using a composite based on platelet rich plasma (PRP), chitosan and hydroxyapatite. The study was approved by the ethics committee of the Federal University of Campina Grande under number 72/2017. Surgical holes measuring four millimetres in diameter were performed in rabbit trochleae, one surgical hole in each animal remained empty and another one was filled with the composite. Clinical-orthopaedic and radiographic evaluations were carried out for 60 days, after which the animals were euthanized for histomorphometric evaluations. Clinical-evaluations exhibited lameness of two members of the treatment (T) group and one member of control (C) group. The radiographic evaluation of T group exhibited absence of subchondral bone reaction (33%); nonetheless, presence of moderate subchondral bone reaction was more frequently reported in group C with 67%. Microscopic evaluation revealed the presence of tissue neoformation, composed of dense connective tissue. Microscopic findings were similar in both groups, with a difference in the amount of neoformed tissue, which was confirmed after the morphometric analysis, revealing a significant difference in the quantity of newly formed tissue at the bone / cartilage / implant interface in the T group. The results indicate that the composite based on chitosan, hydroxyapatite and PRP enhanced bone and cartilage healing