3D-printed orthopedic implants have been gaining popularity in recent years due to the control this manufacturing technique gives the designer over the different design aspects of the implant. This technique allows us to manufacture implants with material properties similar to bone, giving the implant designer the opportunity to address one of the main complications experienced after total hip arthroplasty (THA), i.e. aseptic loosening of the implant. To restore proper function after implant loosening, the implant needs to be replaced. During these revision surgeries, some extra bone is removed along with the implant, further increasing the already present defects, and making it harder to achieve proper mechanical stability with the revision implant. A possible way to limit the increasing loss of bone is the use of biodegradable orthopedic implants that optimize long-term implant stability. These implants need to both optimize the implant such that stress shielding is minimized, and tune the implant degradation rate such that newly formed bone is able to replace the degrading metal in order to maintain a proper bone-implant contact. The hope is that such (partly) degradable implants will lead to a reduction in the size of the bone defects over time, making possible future revisions less likely and less complex. We focused on improving the long-term implant stability of patient-specific acetabular implants for large bone defects and the modeling of their biodegradable behavior. To improve long-term implant stability we implemented a topology optimization approach. A patient-specific finite element model of the hip joint with and without implant was derived from CT-scans to evaluate the performance of the designs during the optimization routine. To evaluate the biodegradation behavior, a quantitative mathematical model was developed to assess the degradation rates of the biodegradable part of the implant. Currently, the biodegradation model has been implemented for magnesium (Mg) implants as a first proof of concept. For a first test case, an optimized implant was found with stress shielding levels below 20% in most regions. The highest stress shielding levels were found at the bone implant interface. The biodegradation model has been validated using experimental data, which includes immersion tests of simple scaffolds created from Commercial Pure Mg. The mass loss of the scaffold is about 0.8 mg/cm. 2. for the first day of immersion in simulated body fluid (SBF) solution. After the formation of a protective film on the surface of the simple scaffold, the degradation rate starts to slow down. Initial results presented serve as a proof of concept of the developed computational framework for the implant optimization and the implant biodegradation behavior. Currently, timing calibration, benchmarking and validation are taking place. Reducing implant-induced stress shielding, obtaining a better implant integration and reduction of bone defects, by allowing for bone to partially replace the implant over time, are crucial design factors for large bone defect implants. In this research, we have developed in-silico models to investigate these factors. Once validated and coupled, the models will serve as an important tool to find the appropriate biodegradable implant designs and biodegradable metal properties for THA applications, that improve current implant lifetime while ensuring proper mechanical functioning

Bioabsorbable metals hold a lot of potential as orthopaedic implant materials. Three metal families are currently being investigated: iron (Fe), magnesium (Mg) and zinc (Zn). Currently, however, biodegradation of such implants is poorly predictable. We thus used Direct Metal Printing to additively manufacture porous implants of a standardized bone-mimetic design and evaluated their mechanical properties and degradation behaviour, respectively, under in vivo-like conditions. Atomized powder was manufactured to porous implants of repetitive diamond unit cells, using a ProX DMP 320 (Layerwise, Belgium) or a custom-modified ReaLizer SLM50 metal printer. Degradation behaviour was characterized under static and dynamic conditions in a custom-built bioreactor system (37ºC, 5% CO. 2. and 20% O. 2. ) for up of 28 days. Implants were characterized by micro-CT before and after in vivo-like degradation. Mechanical characterization (according to ISO 13314: 2011) was performed on an Instron machine (10kN load cell) at different immersion times in simulated body fluid (r-SBF). Morphology and composition of degradation products were analysed (SEM, JSM-IT100, JEOL). Topographically identical titanium (Ti-6Al-4V, Ti64) specimen served as reference. Micro-CT analyses confirmed average strut sizes (420 ± 4 μm), and porosity (64%), to be close to design values. After 28 days of in vivo-like degradation, scaffolds were macroscopically covered by degradation products in an alloy-specific manner. Weight loss after cleaning also varied alloy-specifically, as did the change in pH value of the r-SBF. Corrosion time-dependent changes in Young's moduli from 1200 to 800 MPa for Mg, 1000 to 700 MPa for Zn and 48-8 MPa for iron were statistically significant. In summary, DMP allows to accurately control interconnectivity and topology of implants from all three families and micro-structured design holds potential to optimize their degradation speed. This first systematic report sheds light into how design influences degradation behaviour under in vivo-like conditions to help developing new standards for future medical device evaluation

Aims: To understand why during routine analyses of the physico-chemical properties of retrieved UHMWPE prosthetic components (Pes), it was noticed that some cups, which were directly in contact with bone, evidence a material loss in correspondence with the area adjacent to bone. Methods: PEs retrieved during revision surgery and stored in formalin prior to observation, have been analysed by Fourier Transform InfraRed (FTIR) spectroscopy and Scanning Electron Microscopy (SEM). Results: The results of the FTIR analyses did not display appreciable differences compared to those of the majority of the retrieved prostheses. Oxidation of UHMWPE was detected, but it is known to be due to sterilisation with high energy radiation in air, under uncontrolled conditions. The SEM analyses indicated that the PEs surface which was directly in contact with bone shows an anomalous degradation. The surface looks as it has been corroded or “bitten” and its morphology is significantly different from that of surfaces abraded either in vivo or in vitro. Conclusions: The results so far obtained seem to indicate that the surfaces, which have been in contact with bone during the implant time, undergo a selective biodegradation process, facilitated by gamma in air sterilisation, and influenced by the biological reactivity of the patient (such as osteclast activation)

In the reconstruction of the anterior cruciate ligaments of the knee, early loading of the leg is usually desirable. Thus, it is of a great interest to evaluate the early stability of screws used for tibial fixation of the ligament, rather than long-term stability of such devices when the neoligament is certainly integrated. The purpose of this study (controlled laboratory study) was to investigate the early osteointegration and biodegradation of hydroxyapatite (HA)/poly(L-lactide)(PLLA) (HA/PLLA) composite screws compared with tricalcium-phosphate (TCP)/PLLA (TCP/PLLA) composite screws used for tibial fixation in the reconstruction of the anterior cruciate ligaments. We used two types of resorbable screws: BioRCI (Smith& Nephew) composite screws (30% HA and 70% PLLA) and Biocryl (Mitek) composite screws (30% TCP and 70% PLLA) that were inserted into the distal femur of three skeletally mature sheep. Each animal received one HA/PLLA composite screw and one TCP/ PLLA composite screw. The three sheep were sacrificed 20, 40 and 60 days after surgery. Results were evaluated by radiological (RX, TC and RMN), histological and microradiographic analyses. The amount of bone tissue osteointegrating the screw was higher for TCP/PLLA screws than for HA/PLLA screws. No sign of real biodegradation was observed in any of the specimens. In conclusion, TCP/PLLA composite screws provide a favourable early osteointegration compared to HA/PLLA composite screws; this could provide an early loading of the leg, which is the primary goal of clinicians and patients in this case. In addition, this could provide a considerable reduction of medical expenses, due to the decrease in hospitalisation and rehabilitation time

An injectable material consisting of calcium sulphate mixed with hydroxyapatite was investigated as a possible alternative to autograft in the restoration of bone defects. The material was studied both in vitro in simulated body fluid (SBF) and in vivo when implanted in rat muscles and into the proximal tibiae of rabbits. Variation in the strength and weight of the material during ageing in SBF was measured. Tissue response, material resorption and bone ingrowth were studied in the animal models.

A good tissue response was observed in both the rat muscles and rabbit tibiae without inflammatory reactions or the presence of fibrous tissue. Ageing in SBF showed that during the first week carbonated hydroxyapatite precipitated on the surfaces of the material and this may enhance bone ingrowth.

Introduction Anterior column reconstruction and fusion remains the gold standard of treatment for a number of spinal pathologies. One of the challenges of interbody fusions cages is the footprint of the cage reducing the surface area of endplate available for fusion. Biodegradable polymer implants will over time present a greater area for fusion and may help to reduce problems such as stress shielding, particulate debris and retained foreign body response. Resorbable cages have been have been prepared from a number of different materials, including inorganic composites (eg hydroxyapatite / tricalcium phosphate) and polymers (Poly L-lactide-co-D,L-lactide (PDLLA)). However all of the current options for interbody fusion have reported deficiencies or complications. The synthesis, mechanical properties, and degradation behaviour of two novel biopolymers are presented and the applicability for use as materials in interbody fusion devices is discussed.

Methods Methacrylated adipic anhydride (MAA) and methacrylated sebacic anhydride (MSA) pre-polymers were synthesized by melt condensation. Conversion of the acid to the anhydride was confirmed using 1H nuclear magnetic resonance (NMR) (Bruker, Alexandria, NSW) and FT- Infrared spectroscopy (Nicolet, Waltham MA). These pre-polymers were subsequently co-polymerized with methyl methacrylate (MMA) and 0.25 wt% benzoyl peroxide at 65oC for 16hrs and post-cured at 120oC under vacuum for 2 hrs to form biodegradable networks. The co-polymerization behaviour was monitored by FT-Raman spectroscopy. The compressive mechanical properties of the polymer were determined using an Instron 5567 (Bayswater Vic.). The polymer networks were degraded in phosphate buffered saline (PBS) with various amounts of MAA and MSA.

Results The formation of the pre-polymer was confirmed with the observation of NMR peaks at 5.8 and 6.2 ppm and FT-IR peaks at 1637cm-1. Copolymerization was followed with consecutive FT-IR acquisitions with 100% conversion achieved between 10 and 30 hrs depending on the ratio of MMA to MSA or MAA. Increasing the fraction of methacrylated anhydride slowed the reaction rate.

The compressive strength of the MAA and MSA based copolymers was measured as a function of anhydride concentration. Compressive strength for MMA increased (90±9 to 140±10 Mpa) in an approximately linear manner for MAA concentrations from 10 to 40 wt.% but decreased markedly for MAA concentration of 45% (62±14 Mpa). The compressive strength of MSA decreased exponentially for concentrations ranging from 10 to 45 wt.% (140±18 to 39±1 Mpa).

Discussion The use of poly-L-lactic acid in lumbar interbody cages has been shown to be mechanically feasible with the mechanical strength of the cage material reported to be 93 Mpa (1). The material described here has controlled mechanical properties in the required range as well as a degradation behaviour that lends itself better to spinal applications than current materials

Objectives

Sustained intra-articular delivery of pharmacological agents is an attractive modality but requires use of a safe carrier that would not induce cartilage damage or fibrosis. Collagen scaffolds are widely available and could be used intra-articularly, but no investigation has looked at the safety of collagen scaffolds within synovial joints. The aim of this study was to determine the safety of collagen scaffold implantation in a validated in vivo animal model of knee arthrofibrosis.

Bone defects require implantable graft substitutes, especially porous and biodegradable biomaterial for tissue regeneration. The aim of this study was to fabricate and assess a 3D-printed biodegradable hydroxyapatite/calcium carbonate scaffold for bone regeneration. Materials and methods:. A 3D-printed biodegradable biomaterial containing calcium phosphate and aragonite (calcium carbonate) was fabricated using a Bioplotter. The physicochemical properties of the material were characterised. The materials were assessed in vitro for cytotoxicity and ostegenic potential and in vivo in rat intercondylar Φ3mm bone defect model for 3 months and Φ5mm of mini pig femoral bone defects for 6 months. The results showed that the materials contained hydroxyapatite and calcium carbonate, with the compression strength of 2.49± 0.2 MPa, pore size of 300.00 ± 41mm, and porosity of 40.±3%. The hydroxyapatite/aragonite was not cytotoxic and it promoted osteogenic differentiation of human umbilical cord matrix mesenchymal stem cells in vitro. After implantation, the bone defects were healed in the treatment group whereas the defect of controlled group with gelatin sponge implantation remained non-union. hydroxyapatite/aragonite fully integrated with host bone tissue and bridged the defects in 2 months, and significant biodegradation was followed by host new bone formation. After implantation into Φ5mm femoral defects in mini pigs hydroxyapatite/aragonite were completed degraded in 6 months and fully replaced by host bone formation, which matched the healing and degradation of porcine allogenic bone graft. In conclusion, hydroxyapatite/aragonite is a suitable new scaffold for bone regeneration. The calcium carbonate in the materials may have played an important role in osteogenesis and material biodegradation

The ideal bone substituting biomaterials should possess bone-mimicking mechanical properties; have of porous interconnected structure, and adequate biodegradation behaviour to enable full recovery of bony defects. Direct metal printed porous scaffolds hold potential to satisfy all these requirements and were additively manufactured (AM) from atomized WE43 magnesium alloy powder with grain sizes between 20 and 60 μm. Their micro-structure, mechanical properties, degradation behavior and biocompatibility was then evaluated in vitro. Firstly, post-processing values nicely followed design parameters. Next, Young's moduli were similar to that of trabecular bone (i.e., E = 700–800 MPa) even after 28 days of simulated in vivo-like corrosion by in vitro immersion. Also, a relatively moderate hydrogen evolution, corresponding to a calculated 19.2% of scaffold mass loss, was in good agreement with 20.7% volume reduction as derived from reconstructed μCT images. Finally, only moderate cytotoxicity (i.e., level 0, <25%), even after extensive ISO 10993-conform testing for 72 h using MG-63 cells, was determined using WE43 extracts (2 way ANOVA, post-hoc Tukey's multiple comparisons test; α = 0.05). Cytotoxicity was further evaluated by direct live-dead staining assays, revealing a higher cell death in static culture. However, intimate cell-metal contact was observed by SEM. In summary, while pure WE43 may not yet be an ideal surface for cell adhesion, this novel AM process allows for adjusting biodegradation through topological design. Our approach holds tremendous potential to develop functional and biodegradable implants for orthopaedic applications

In a rabbit model we investigated the efficacy of a silk fibroin/hydroxyapatite (SF/HA) composite on the repair of a segmental bone defect. Four types of porous SF/HA composites (SF/HA-1, SF/HA-2, SF/HA-3, SF/HA-4) with different material ratios, pore sizes, porosity and additives were implanted subcutaneously into Sprague-Dawley rats to observe biodegradation. SF/HA-3, which had characteristics more suitable for a bone substitite based on strength and resorption was selected as a scaffold and co-cultured with rabbit bone-marrow stromal cells (BMSCs). A segmental bone defect was created in the rabbit radius. The animals were randomised into group 1 (SF/HA-3 combined with BMSCs implanted into the bone defect), group 2 (SF/HA implanted alone) and group 3 (nothing implanted). They were killed at four, eight and 12 weeks for visual, radiological and histological study. The bone defects had complete union for group 1 and partial union in group 2, 12 weeks after operation. There was no formation of new bone in group 3. We conclude that SF/HA-3 combined with BMSCs supports bone healing and offers potential as a bone-graft substitute

Direct metal printed (DMP) porous iron implants possess promising mechanical and corrosion properties for various clinical application. Nevertheless, there is a requirement for better co-relation between in vitro and in vivo corrosion and biocompatibility behaviour of such biomaterials. Our present study evaluates absorption of porous iron implants under both static and dynamic conditions. Furthermore, this study characterizes their cytocompatibility using fibroblastic, osteogenic, endothelial and macrophagic cell types. In vitro degradation was performed statically and dynamically in a custom-built set-up placed under cell culture conditions (37 °C, 5% CO2 and 20% O2) for 28 days. The morphology and composition of the degradation products were analysed by scanning electron microscopy (SEM, JSM-IT100, JEOL). Iron implants before and after immersion were imaged by μCT (Quantum FX, Perkin Elmer, USA). Biocompatibility was also evaluated under static and dynamic in vitro culture conditions using L929, MG-63, HUVEC and RAW 264.7 cell lines. According to ISO 10993, cytocompatibility was evaluated directly using live/dead staining (Live and Dead Cell Assay kit, Abcam) in dual channel fluorescent optical imaging (FOI) and additionally quantified by flow cytometry. Furthermore, cytotoxicity was indirectly quantified using ISO conform extracts in proliferation assays. Strut size of DMP porous iron implants was 420 microns, with a porosity of 64% ± 0.2% as measured by micro-CT. After 28 days of physiological degradation in vitro, dynamically tested samples were covered with brownish degradation products. They revealed a 5.7- fold higher weight loss than statically tested samples, without significant changes in medium pH. Mechanical properties (E = 1600–1800 MPa) of these additively manufactured implants were still within the range of the values reported for trabecular bone, even after 28 days of biodegradation. Less than 25% cytotoxicity at 85% of the investigated time points was measured with L929 cells, while MG-63 and HUVEC cells showed 75% and 60% viability, respectively, after 24 h, with a decreasing trend with longer incubations. Cytotoxicity was analysed by two-way ANOVA and post-hoc Tukey's multiple comparisons test. Under dynamic culture conditions, live-dead staining and flow cytometric quantification showed a 2.8-fold and 5.7-fold increase in L929 and MG-63 cell survival rates, respectively, as compared to static conditions. Therefore, rationally designed and properly coated iron-based implants hold potential as a new generation of absorbable Orthopaedic implants

The treatment of critical-sized bone defects still remains today a challenge, especially when the surrounding soft, vascularized and innervated tissues have been damaged - a lack of revascularization within the injured site leading to physiological disorders, from delayed healing to osteonecrosis. The axial insertion of a vascular bundle (e.g. arterio-venous loop, AVL) within a synthetic bone filler to initiate and promote its revascularization has been foreseen as a promising alternative to the current strategies (e.g., vascularized free flaps) for the regeneration of large bone defects. In a previous work, we showed that the insertion of a vein in a 3D-printed monetite scaffold induced its higher revascularization than AVL, thus a possible simplification of the surgical procedures (no microsurgery required). Going further, we investigate in this study whether or not the presence of a vein could stimulate the formation of mineralized tissue insides a synthetic scaffold filled with bone marrow and implanted in ectopic site. Monetite scaffolds were produced by additive manufacturing according to a reactive 3D-printing technique co-developed by the authors then thoroughly characterized. Animal study was performed on 14 male Wistar rats. After anesthesia and analgesia, a skin medial incision in rat thigh allowed the site on implantation to be exposed. Bone marrow was collected on the opposite femur through a minimally invasive procedure and the implant was soaked with it. For the control group (N=7), the implant was inserted in the incision and the wound was closed whereas the femoral bundle was dissected and the vein inserted in the implant for the experimental group (N=7). After 8 weeks animals were sacrificed, the implant collected and fixed in a 4% paraformaldehyde solution. Explants were characterized by µCT then embedded in poly-methyl methacrylate prior SEM, histology and immunohistochemistry. Images were analyzed with CT-Analyzer (Bruker) and ImageJ (NIH) and statistical analyses were carried out using SPSS (IBM). Implants were successfully 3D-printed with a +150 µm deviation from the initial CAD. As expected, implants were composed of 63%wt monetite and 37%wt unreacted TCP, with a total porosity of 44%. Data suggested that scaffold biodegradation was significantly higher when perfused by a vein. Moreover, the latter allowed for the development of a dense vascular network within the implant, which is far more advanced than for the control group. Finally, although mineralized tissues were observed both inside and outside the implant for both groups, bone formation appeared to be much more important in the experimental one. The ectopic formation of a new mineralized tissue within a monetite implant soaked with bone marrow seems to be highly stimulated by the simple presence of a vein alone. Although AVL have been studied extensively, little is known about the couple angiogenesis/osteogenesis which appears to be a key factor for the regeneration of critical-sized bone defects. Even less is known about the mechanisms that lead to the formation of a new bone tissue, induced by the presence of a vein only. With this in mind, this study could be considered as a proof of concept for further investigations

Purpose: The objective of this project is to determine the suitability of modified fibrin hydrogels as scaffolds for articular cartilage tissue engineering. The attractive feature of the fibrin system is that the gel precursors are available in autologous form. We have previously demonstrated that genipin, a naturally occurring cross-linking agent, stabilizes the fibrin gel. Methods: Human articular chondrocytes were isolated from articular cartilage harvested from consenting patients undergoing total knee arthroplasty. The human cells were encapsulated into fibrin gels where gelation was induced by combining fibrinogen, thrombin, and genipin. The resulting gels were evaluated for extracellular matrix (ECM) production, mechanical properties, cell viability, and biodegradation. Results: No breakdown of the gels was detected during 5 weeks of cell culture. After several weeks in culture, histology indicates significant proteoglycan production by encapsulated cells, and collagen II and aggrecan were detected in this ECM by immunostaining. There was a greater accumulation of cartilage-like ECM in the gels cross-linked with genipin. Dynamic compression tests performed at 0.1 Hz for 10 cycles using an MTS machine indicate that accumulation of ECM was associated with increased stiffness of the material. Cell viability was assessed using live/dead staining, and was found to be > 50% after 24 hours and at 1 week in culture. The presence of genipin cross-linking did not significantly affect cell viability. Real-Time RT-PCR indicated that encapsulated chondrocytes show an increase in Sox9, collagen II and aggrecan expression over 5 weeks and that this is further increased in the presence of genipin. The gene expression results agreed with the enhanced ECM seen under these conditions by histology and immunostaining. The fibrin material was also implanted subcutaneously into rats and after 30 days the material was removed, sectioned and evaluated. Immunostaining indicated that while there was evidence of biodegradation, the material did not appear to cause an inflammatory response. Conclusions: Modified fibrin hydrogels show potential as cellular scaffolds for articular cartilage tissue engineering. An in vivo orthopaedic model must now be developed to fully evaluate the potential of the fibrin gel. Funding: Other Education Grant

Biodegradable metals as orthopaedic implant materials receive substantial scientific and clinical interest. Marketed cardiovascular products confirm good biocompatibility of iron. Solid iron biodegrades slowly in vivo and has got supra-physiological mechanical properties as compared to bone and porous implants can be optimized for specific orthopaedic applications. We used Direct Metal Printing (DMP)3 to additively manufacture (AM) scaffolds of pure iron with fine-tuned bone-mimetic mechanical properties and improved degradation behavior to characterize their biocompatibility under static and dynamic 3D culture conditions using a spectrum of different cell types. Atomized iron powder was used to manufacture scaffolds with a repetitive diamond unit cell design on a ProX DMP 320 (Layerwise/3D Systems, Belgium). Mechanical characterization (Instron machine with a 10kN load cell, ISO 13314: 2011), degradation behavior under static and dynamic conditions (37ºC, 5% CO2 and 20% O2) for up of 28 days, with μCT as well as SEM/energy-dispersive X-ray spectroscopy (EDS) (SEM, JSM-IT100, JEOL) monitoring under in vivo-like conditions. Biocompatibility was comprehensively evaluated using a broader spectrum of human cells according to ISO 10993 guidelines, with topographically identical titanium (Ti-6Al-4V, Ti64) specimen as reference. Cytotoxicity was analyzed by two-way ANOVA and post-hoc Tukey's multiple comparisons test (α = 0.05). By μCT, as-built strut size (420 ± 4 μm) and porosity of 64% ± 0.2% were compared to design values (400 μm and 67%, respectively). After 28 days of biodegradation scaffolds showed a 3.1% weight reduction after cleaning, while pH-values of simulated body fluids (r-SBF) increased from 7.4 to 7.8. Mechanical properties of scaffolds (E = 1600–1800 MPa) were still within the range for trabecular bone, then. At all tested time points, close to 100% biocompatibility was shown with identically designed titanium (Ti64) controls (level 0 cytotoxicity). Iron scaffolds revealed a similar cytotoxicity with L929 cells throughout the study, but MG-63 or HUVEC cells revealed a reduced viability of 75% and 60%, respectively, already after 24h and a further decreased survival rate of 50% and 35% after 72h. Static and dynamic cultures revealed different and cell type-specific cytotoxicity profiles. Quantitative assays were confirmed by semi-quantitative cell staining in direct contact to iron and morphological differences were evident in comparison to Ti64 controls. This first report confirms that DMP allows accurate control of interconnectivity and topology of iron scaffold structures. While microstructure and chemical composition influence degradation behavior - so does topology and environmental in vitro conditions during degradation. While porous magnesium corrodes too fast to keep pace with bone remodeling rates, our porous and micro-structured design just holds tremendous potential to optimize the degradation speed of iron for application-specific orthopaedic implants. Surprisingly, the biological evaluation of pure iron scaffolds appears to largely depend on the culture model and cell type. Pure iron may not yet be an ideal surface for osteoblast- or endothelial-like cells in static cultures. We are currently studying appropriate coatings and in vivo-like dynamic culture systems to better predict in vivo biocompatibility

Tissue engineering is a promising approach to regenerate damaged skeletal tissues. In particular, the use of injectable hydrogels alleviates common issues of poor cell viability and engraftment. However, uncontrolled cell fate, resulting from unphysiological environments and degradation rates, still remain a hurdle and impedes tissue healing. We thus aim at developing a new platform of injectable hyaluronic acid (HA) hydrogels with a large panel of properties (stiffness, degradation…) matching those of skeletal tissues. Hence, HA with different molecular weights were functionalized with silylated moieties. Upon injection, these hydrogels formed through a sol-gel chemistry within 5 to 20 minutes in physiological conditions, as demonstrated by rheological characterization. By varying the crosslinking density and concentration, we obtained hydrogels spanning a large range of elastic moduli (E = 0.1–20 kPa), similar to those of native ECMs, with tunable biodegradation rates (from 24 hours to > 50 days) and swelling ratios (500 to 5000% (w/w)). Cell viability was confirmed by Live/Dead assays and will be completed by in vivo subcutaneous implantations in mice to study the foreign body reaction and degradation rate. We further developed hybrid HA/biphasic calcium phosphate granules hydrogels and demonstrated a strong mechanical reinforcement (E = 0.1 MPa) and a faster relaxation behaviour (τ. 1/2. < 400s), with similar degradation rates. Ongoing in vitro differentiation assays and in vivo implantations in a rabbit femur model will further assess their ability to drive bone regeneration. Collectively, these results suggest that this hydrogel platform offers promising outcomes for improved strategies in skeletal tissue engineering

Objectives. Total hip arthroplasty (THA) is one of the most successful surgical procedures; several bearing technologies have been used, however none of these is optimal. Metal on polycarbonate-urethane (PCU) is a new bearing technology with several potential advantages: PCU is a hydrophilic soft pliable implant quite similar in elasticity to human cartilage, offers biostability, high resistance to hydrolysis, oxidation, and calcification, no biodegradation, low wear rate and high corrosion resistance and can be coupled with large metal heads (Tribofit Hip System, THS). The aim of this prospective study was to report the survivorship and the clinical and radiographic outcomes and the metal ions dosage of a group of patients operated with metal on PCU arthroplasty featuring large metal diameter heads, at 5 years from surgery. Study Design & Methods. 68 consecutive patients treated with the THS were included. The patients have been contacted by phone call and invited to return to our centre for clinical (Oxford Hip Score, OHS, and Harris Hip Score, HHS), radiographic exam and metal ion levels evaluation. All the patients were operated with uncemented stems. Results. The survival rate is 100% and no major complications were seen. The average preoperative OHS was 17 (6–34), at follow-up it was 44 (40–48). The average preoperative HHS was 48 (12–76), at follow-up it was 93 (84–100). On the x rays taken at follow-up, no signs of periprosthetic bone rarefaction and/or osteolysis were seen. No signs of PCU liner wear were visible. At follow up mean Co serum level was 0.52 ng/mL (<0.1–2.5, sd 0.5), mean Cr level was 0.27 ng/mL (0.1–2.2, sd 0.2). In this prospective study at a mean follow up of 5 years, all implants were well functioning, with no radiological signs of loosening and normal serum levels of cobalt and chrome. Although large diameter metal heads and metal sleeve were used no trunnionosis occurred. Conclusions. We believe that these positive outcomes are due the positive biomechanical characteristics of PCU. These results need to be confirmed at a longer follow up and in a more active younger patient population

Successful reconstruction of bone defects requires an adequate filling material that supports regeneration and formation of new bone within the treated defect in an optimal fashion. Currently available synthetic bone graft substitutes cannot fulfill all requirements of the highly complex biological processes involved in physiological bone healing. Due their unphysiologically asynchronous biodegradation properties, their specific foreign material-mediated side effects and complications and their relatively modest overall osteogenic potential, their overall clinical performance typically lags behind conventional bone grafts of human origin. However, defect- and pathology specific combination of synthetic bone graft substitutes exhibiting appropriate carrier properties with therapeutic agents and/or conventional bone graft materials allows creation of biologically enhanced composite constructs that can surpass the biological and therapeutic limits even of autologous bone grafts. This presentation introduces a bone defect reconstruction concept based on biological enhancement of optimal therapeutic agent-carrier composites and provides a rationale for an individual, requirement-specific adaptation of a truly patient-specific reconstruction of bone defects. It represents the pinnacle of the bone defect reconstruction pyramid, founded on the basic principles and prerequisites of complete elimination of the underlying pathology, preservation, augmentation or restoration of mechanical stability of the treated bone segment and creation of a biodegradable scaffold with adequate mechanical integrity. It summarises the current body of relevant experimental and clinical research, presents clinical case examples illustrating the various aspects of the proposed concept as well as early clinical results. The author hopes that the theoretical and conceptual framework provided, will help guide future research as well as clinical decision making with respect to this particular field

Aim. A gentamicin-eluting biocomposite consisting of hydroxyapatite (HA) and calcium sulphate (CaS)*1 can provide effective dead space management and bone formation in chronic osteomyelitis. However, radiographic follow-up after implantation of this biomaterial has shown imaging features previously not described with other comparable bone graft substitutes. Last year we presented preliminary results with a follow-up of 6 months. Now we present the radiographic, µCT and histological one-year follow-up of the critical-size bone defect model in sheep. The aim of this study was to simulate the clinical situation in a large animal model to correlate different imaging techniques used in the clinic (Radiography, CT and MRI scans) with histological finding. Methods. Standardised bone defects were created in ten Merino-wool sheep (age two to four years). Large drill holes (diameter 2.5cm, depth 2cm, volume approx. 10ml) were placed in the medial femoral condyles of both hind legs and filled with gentamicin-eluting biocomposite. Initially surgery was carried out on the right hind leg. Three months later, an identical intervention was performed on the contralateral side. Animals were sacrificed at three and six weeks and 4.5, six and twelve months. Radiographs and MRI scans were taken immediately after sacrifice. Filled bone voids were harvested en-block and analysed using µCT, and histology. Results. We present our radiographic, µCT and histological results after a follow-up of twelve months. The bio-composite was clearly visible on all post-operative radiographs and resorbed over the next four months following the before described pattern of “halo sign” and “marble sign”. µCT images of the “halo sign” show degradation of the biocomposite starting at its surface, with the degradation products CaS and HA carried into the periphery of the bone void. µCT images of the “marble sign” showed the further degradation of the biocomposite from the surface to its core, leaving a “marble shaped” remnant of the biocomposite behind. These remnants are completely resorbed at 4.5 months. µCT scans at twelve and six months' reveal progression of trabecula bone formation. The histological results confirm the µCT findings. Conclusion. We have established a large animal model, which mimics the clinical situation and reproduces comparable radiographic post implantation features previously observed in clinical cases (including the “halo” and the “marble” sign). Using µCT imaging and histology we can describe and understand the biodegradation process and the bone formation capacity of the biocomposite in detail. *1 CERAMENTTM|G, BONESUPPORT, Lund, Sweden. *2 CERAMENTTM|G

Introduction: The Optiplug. ®. bio-absorbable cement restrictor, marketed by Biomet inc., is manufactured from ‘PolyActive’ – a polymer of poly(ethylene glycol) and butylene terephthalate. Biodegradation is thought to be by a combination of hydrolysis and oxidation. The potential benefit – eliminating the need for restrictor removal at future revision surgery – led to Optiplug becoming our cement restrictor of choice over the last 5 years. Anecdotally we have seen marked osteolysis around the distal cement mantle in a number of follow up radiographs in these patients. To date we have not seen an associated peri-prosthetic fracture. We undertook a retrospective, radiographic study to determine incidence, severity and progression of this osteolysis over the first 5 years of follow up. Method: 100 patients for whom 5 year follow up had been undertaken were identified from the departmental database. Patients with loose prostheses and or infection were excluded as were those who had undergone revision surgery. Radiographs from the immediate post operative period, twelve months and five years follow up visits were identified and reviewed. Osteolysis was quantified by calculating the ratio of maximum medullary diameter to the overall cortical diameter of the bone. Comparison was made over time and, where radiographs allowed, to the immediately adjacent femur. Results: 87% of radiographs showed greater than 10% thinning of the cortex at 1 year cf. immediate post op. 5 cases showed greater than 33% thinning. These changes do not appear to progress or regress significantly between 1 and 5 years. Discussion: While marked osteolytic changes appear to be uncommon, some degree of cortical thinning was almost universal in this series. The zone immediately distal to the cement mantle is commonly involved in peri-prosthetic fractures. Any weakening in this area is undesirable

Although alumina has been used in orthopaedic surgery since the 1970s, the long-term clinical results of zirconia have not been well documented in vivo. We studied hips with these two different ceramics during the same period and with a minimum follow-up of ten years. Because the size of the alumina and zirconia heads was different, hips with 32 mm alumina heads and those with 28 mm zirconia heads were compared with control hips with stainless-steel heads of the same size. Our aim was to compare the two ceramics. There was an increased linear rate of penetration of the femoral heads into the liner between years five and 12 for the zirconia and the stainless-steel groups. This was severe in the zirconia group (0.4 mm/year compared with 0.13 mm/year for the stainless-steel group). During the same 12-year period there was, however, no significant change in the rate of wear in the alumina group (0.07 mm/year). The mean wear at the most recent follow-up was 1360 mm. 3. for the 28 mm zirconia group, 683 mm. 3. for the 28 mm stainless-steel group, 755 mm. 3. for the 32 mm alumina group and 1314 mm. 3. for the 32 mm stainless-steel group. The monoclinic content rose on the surface of three zirconia heads which were retrieved at revision. This change was associated with an increase in the surface roughness. A change in the roundness with an increase in the sphericity deviation was also observed both in the articular and non-articular parts of the femoral heads. The increase in rate of wear in the zirconia group was only evident after eight years and may be linked to a long-term biodegradation of zirconia in vivo, associated with the altered roughness and roundness which was observed on the retrieved heads