Introduction. Management of open fractures is challenging and requires a multidisciplinary team approach. Gustilo Anderson Type IIIB fractures reportedly have a higher infection rate (up to 52%) and up to 16% amputation rate. This study aims to evaluate outcomes of using Adjuvant Local Antibiotic Hydroxyapatite Bio-Composite in management of Open Gustilo-Anderson IIIB fractures. Materials and Methods. We reviewed a prospective data of 80 patients who presented with Gustilo Anderson Type IIIB Open Fracture to a single ortho-plastic centre. Only patients who were managed with single-stage “Fix and Flap” along with intra-operative Adjuvant Local Antibiotic Bio-Composite were included. Results. Mean follow-up time was 22 months. The mean time from injury until definitive surgery was 7.73 days (1–30 days). Primary union achieved in 88.3% within 32 weeks on average. The delayed union reported in 7.8% of patients, for the bone healing stimulated by injecting the fracture site with Autologous Bone Marrow Aspirate Concentrate. Subsequent follow-up showed signs of successful fracture healing at 60 weeks post-injury. Three patients (3.9%) had non-union. Limb salvage rate was 96.25%, and only 1.25% deep infection rate. Conclusions. Our results highlight that low infection rates, high limb salvage rates and high union rates can be achieved in these complex injuries with a combined OrthoPlastic approach, MDT input, meticulous technique and the use of adjuvant local antibiotic bio-composite. Delay in definitive surgery, gentamicin resistance and smoking were not associated with any increased deep infection or non-union in our series. At 22 months of follow-up, deep infection rate was 1.25%, limbs salvage rate was 96.25%, fracture union rate was 96.1%, and reoperation rate 18.75%

Introduction. An increasing trend in the incidence of primary and revision bone replacements has been observed throughout the last decades, mainly among patients under 65 years old.10-year revision rates are estimated in the 5–20% range, mainly due to peri-implant bone loss. Recent advances allow the design of implants with custom-made geometries, nanometer-scale textured surfaces and multi-material structures. Technology also includes (bio)chemical modifications of the implants' surfaces. However, these approaches present significant drawbacks, as their therapeutic actuations are unable to: (1) perform long-term release of bioactive substances, namely after surgery; (2) deliver personalized stimuli to target bone regions and according to bone-implant integration states. The Innovative Concept. Here we propose the design of instrumented active implants with ability to deliver personalized biophysical stimuli, controlled by clinicians, to target regions in the bone-implant interface throughout the patients' lifetime. The idea is to design bone implants embedding actuators, osseointegration sensors, wireless communication and self-powering systems. This work proposes an advanced therapeutic actuator for personalized bone stimulation, and a self-powering system to electrically supply these advanced implants. Novel Capacitive Stimulators and Self-Powering Systems. A novel circular capacitive stimulator was designed for personalized stimulatory therapies based on the delivery of electric fields to bone cells. Its architecture is composed by 3 coplanar electrodes, 2 mm wide, 1 mm thick, and 0.5 mm apart from each other. It enables the delivery of controllable stimuli, as different stimuli (varying waveform, strength, frequency, etc.) can be delivered to target regions of bone. Numerical biophysical models were developed using COMSOL Multiphysics (v. 5.2) to analyze the osteogenic effects of stimulation delivered in vitro to MC3T3-E1 bone cells. 8 domains (electrodes, petri dish, substrate, air, cellular medium and physiological medium) were considered to simulate an apparatus to stimulate cell cultures. Simulations were carried out by applying low and high frequency (14 Hz and 60 kHz) sinusoidal excitations with 10 V of amplitude. A motion-driven and maintenance-free self-powering system was designed using magnetic levitation-based electromagnetic energy harvesting. A semi-analytical non-linear mathematical model of its complex energy transduction was developed (it includes modelling of the magnetic field produced by levitating hard magnetic elements, repulsive force between two magnets, electrical and mechanical damping, induced voltage, mechanical and electric dynamics) to estimate the energy harvested during gait patterns. Results. This cosurface stimulator is able to deliver similar magnitude stimuli to bone cells as those already recognized as osteogenic by previous studies. Heterogeneous stimuli is delivered both for low and high excitations, although quite different stimuli distributions are found along the cellular layer. Maximum stimuli occur over the electrode-anode region and its magnitude is approximately 0.3 V/mm. The electrode thickness influence must also be highlighted: the use of electrodes with 0.1 mm thick result in 2.5-fold magnitude increases in high-frequency stimulation. Excellent agreement was obtained between simulations and experiments with mean energy errors around 6% and cross-correlations higher than 85%. These results indicate that the design of this self-powering system can be optimized prior to fabrication and according to gait patterns of patients

This study reviewed all patients who received an EXOGEN Express bone stimulating device (BSD) to treat delayed union / non-union following operative treatment for a long bone fracture & evaluate if our results are comparable with the NICE guideline expectations. A retrospective review of records between December 2004 & January 2013 revealed 113 patients treated with a BSD. A total of 59 patients were eligible for analysis, (operative treatment for a long bone fracture with adjuvant EXOGEN BSD for non-union or delayed union). Twenty-one were open fractures. The BSD was applied at a mean of 264 days post-operatively. Thirty-five patients went on to have a 2nd operation before union was achieved. Forty-two patients went on to union following application of the BSD. Mean time to union was 293 days. Seventeen patients failed to unite by the end of the study. There were no adverse reactions to the EXOGEN BSD in this cohort. This study has shown that the use of an EXOGEN BSD is a safe, non-invasive method to successfully treat long bone non-unions following initial operative surgery, with potential cost savings (a potential saving of £48,888 to the hospital according to NICE estimations) compared to the standard re-operative management

Introduction. Bone marrow stimulation has been a successful treatment option in cartilage repair and microfracture was the procedure of choice since the late 1980s. Despite its success in young and active patients, microfracture has inherent shortcomings such as shallow channels, wall compression, and non-standardized depth and diameter. This in vitro study assessed bone marrow access comparing microfracture, 1 and 2mm K-Wires, 1mm drill, and a recently introduced standardized subchondral bone needling procedure (Nanofracture) that creates 9mm deep and 1mm wide channels. Methods. An adult ovine model was used to assess access to bone the marrow spaces as well as effects on bone following microfracture, nanofracture, K-wire, and drilling following ethical clearance. All bone marrow stimulation techniques were conducted on a full thickness articular cartilage defect on the medial femoral condyles by the same surgeon. The same groups were repeated in vitro in 4 paired ovine distal femurs. MicroCT (Inveon Scanner, Siemens, Germany) was performed using 3D reconstruction and 25 micron slice analysis (MIMICS, Materialise, Belgium). Results. Microfracture elicited shallow depth with bone compression surrounding the channels. Trabecular channel access was limited; the channel depth and diameter were non-standardized and highly user and instrument dependent. Nanofracture demonstrated deep cancellous bone perforation with a high number of open trabecular channels. K-Wire drilling with both diameters resulted in well-defined channel walls, outlined by fine osseous deposits. Trabecular channel access was limited. The diameter of bone perforation is standardized, but depth is defined by visual controls. 1mm drill bit reaming demonstrated better osseous evacuation, but still limited trabecular marrow access. Discussion and Conclusion. Nanofracture resulted in thin, fragmented cancellous bone channels without rotational heat generation. Compared to microfracture, drilling and K-Wire stimulation, nanofracture showed superior bone marrow access with multiple trabecular access channels extending 9mm into subchondral bone

The management of upper limb nonunions can be challenging and often with unpredictable outcomes. In the study we present the results of treatment of upper limb nonunions treated in our institution with BMP-7 biological enhancement. Between 2004 and 2011 all consecutive patients who met the inclusion criteria were followed up prospectively. Union was assessed with regular radiological assessment. At the final follow up clinical assessment included the disabilities of the Arm, Shoulder and Hand (DASH) score, range of movement and patient satisfaction. The mean follow up was 12 months (12–36). In total 42 patients met the inclusion criteria with a mean age of 47. Anatomical distribution of the nonunion sites included 19 cases of mid/proximal radius/ulna, 14 humerus, 6 distal radius and 3 clavicles. 5 patients had septic nonunion, 35 had atrophic nonunion, 11 had previous open fractures, and 10 had bone loss (range 1–3 cm). The mean number of operations performed and the mean time from injury to BMP application was 1.5 and 26 months, respectively. 40 patients had both clinical and radiological union whereas 2 had partial radiological union but a pain free range of motion. BMP was applied in isolation in 1 case and 41 cases the application was combined with autologous bone grafting. The range of movement of the affected limb, DASH score and patient satisfaction were optimum at the final follow up. This study supports the use of BMP-7 as a bone stimulating adjunct for the treatment of complex and challenging upper limb nonunions

The purpose of this study was to evaluate the efficacy of human recombinant osteogenic protein 1 (rhBMP-7) for the treatment of fracture non-unions and to estimate the health economics aspect of its administration. Twenty-four patients (18 males, mean age 39.1 (range 18-79)) with 25 fracture non-unions were treated with rhBMP-7 in our institution (mean follow-up 15.4 months (range 6-29)). Successful completion of treatment was defined as the achievement of both clinical and radiological union. The cost of each treatment episode was estimated including hospital stay, theatre time, orthopaedic implants, drug administration, investigations, clinic attendances, and physiotherapy treatments. The total cost of all episodes up to the point of receiving BMP-7 and similarly following treatment with BMP-7 were estimated and analysed. Of the 25 cases, 21 were atrophic (3 associated with bone loss) and 4 were infected non-unions. The mean number of operations performed prior to rhBMP-7 application was 3.4, including autologous bone graft in 9 cases and bone marrow injection in one case. In 21 out of the 25 cases (84%), both clinical and radiological union occurred. Mean hospital stay before and after receiving rhBMP-7 was 26.84 days per fracture and 7.8 days per fracture respectively. Total cost of treatments prior to BMP-7 was £346,117 [£13,844.68 per fracture]. Costs incurred following BMP-7 administration were estimated as £183,460 [£7,338.4 per fracture]. rhBMP-7 was used as a bone stimulating agent with or without conventional bone grafting with a success rate of 84% in this series of patients with persistent fracture non-unions. The average cost of its application was £7,338 [53.0% of the total costs of previous unsuccessful treatment of non –unions, p<0.05). Treating non-union is costly, but the financial burden could be reduced by early rhBMP-7 administration when a complicated or persistent non-union is present or anticipated. Therefore, this study supports the view that rhBMP-7 is a safe and power adjunct to be considered in the surgeon's armamentarium for the management of such difficult cases

PURPOSE. Recently, in tissue engineering several methods using stem cells have been developed to repair chondral and osteochondral defects. Most of these methods rely on the use of scaffolds. Studies in the literature have demonstrated, first in animals and then in humans, that the use of mesenchymal stem cells withdrawn by several methods from adipose tissue allows to regenerate hyaline articular cartilage. In fact, it has been cleared that adipose-derived cells have multipotentiality equivalent to bone marrow-derived stem cells and that they can very easily and very quickly be isolated in large amounts enabling their immediate use in operating room for one-step cartilage repair techniques. The purpose of this study is to evaluate the therapeutic effect of adipose-derived stem cells on cartilage repair and present our experience in the treatment of knee cartilage defects by the novel AMIC REPAIR TECHNIQUE AUGMENTED by immersing the collagen scaffold with mesenchymal stem cells withdrawn from adipose tissue of the abdomen. MATERIALS AND METHODS. Fat tissue processing involves mechanical forces and does not mandatorily require any enzymatic or chemical treatment in order to obtain the regenerative cells from the lipoaspirate. In our study, mesenchymal adipose stem cells were obtained by non-enzymatic filtration or microfragmentation of lipoaspirates of the abdomen adipose tissue that enabled the separation of the stromal vascular fraction and were used in one-step reconstruction of knee cartilage defects by means of this new AUGMENTED AMIC TECHNIQUE. The focal defects underwent bone marrow stimulation microfractures, followed by coverage with collagen double layer resorbable membrane (Chondro-gide. TM. -Geistlich Pharma AG, Wolhusen, Switzerland) soaked in the cells obtained from fat in 18 patients, aged between 31 and 58 years, at the level of the left knee in 10 cases and in the right in eight, with follow-up ranging between 12 and 36 months. RESULTS: Surgical procedures have been completed without technical problems neither intraoperative or early postoperative complications. The evaluation scores (IKDC, KOOS and VAS) showed a significant improvement, more than 30%, at the initial 6 months follow-up and furtherly improved in the subsequent follow-ups. Also the control MRIs showed a progressive filling and maturation of the repair tissue of the defects. CONCLUSIONS. Since we are reporting a short and medium-term experience, it is not, of course, possible to provide conclusive assessment considerations on this technique, as the experience has to mature along with the progression of follow-ups. The simplicity together with the absence of intraoperative difficulties or immediate complications and the experience gained by other authors, first in animals and then in early clinical cases, makes it, however, possible to say that this can be considered one of the techniques to which resort for one-step treatment of cartilage defects in the knee because it improves patient's conditions and has the potential to regenerate hyaline-like cartilage. Future follow-up works will confirm the results

Biomaterials used in regenerative medicine should be able to support and promote the growth and repair of natural tissues. Bioactive glasses (BGs) have a great potential for applications in bone tissue engineering [1, 2]. As it is well known BGs can bond to host bone and stimulate bone cells toward osteogenesis. Silicate BGs, e.g. 45S5 Bioglass® (composition in wt.%: 45 SiO. 2. , 6 P. 2. O. 5. , 24, 5 Na. 2. O and 24.5 CaO), exhibit positive characteristics for bone engineering applications considering that reactions on the material surface induce the release of critical concentrations of soluble Si, Ca, P and Na ions, which can lead to the up regulation of different genes in osteoblastic cells, which in turn promote rapid bone formation. BGs are also increasingly investigated for their angiogenic properties. This presentation is focused on cell behavior of osteoblast-like cells and osteoclast-like cells on BGs with varying sample geometry (including dense discs for material evaluation and coatings of highly porous Al. 2. O. 3. -scaffolds as an example of load-bearing implants). To obtain mechanically competent porous samples with trabecular architecture analogous to those of cancellous bone, in this study Al. 2. O. 3. scaffolds were fabricated by the well-known foam replication method and coated with Bioglass® by dip coating. The resulted geometry and porosity were proven by SEM and μCT. Originating from peripheral blood mononuclear cells formed multinucleated giant cells, i.e. osteoclast-like cells, after 3 weeks of stimulation with RANKL and M-CSF. Thus, the bioactive glass surface can be considered a promising material for bone healing, providing a surface for bone remodeling. Osteoblast-like cells and bone marrow stromal cells were seeded on dense bioactive glass substrates and coatings showing an initial inhibited cell attachment but later a strong osteogenic differentiation. Additionally, cell attachment and differentiation studies were carried out by staining cytoskeleton and measuring specific alkaline phosphatase activity. In this context, 45S5 bioactive glass surfaces can be considered a highly promising material for bone tissue regeneration, providing very fast kinetics for bone-like hydroxyapatite formation (mineralization). Our examinations revealed good results in vitro for cell seeding efficacy, cell attachment, viability, proliferation and cell penetration onto dense and porous Bioglass®-coated scaffolds. Recent in vivo investigations [3] have revealed also the angiogenic potential of bioactive glass both in particulate form and as 3D scaffolds confirming the high potential of BGs for bone regeneration strategies at different scales. Implant surfaces based on bioactive glasses offer new opportunities to develop these advanced biomaterials for the next generation of implantable devices and tissue scaffolds with desired tissue-implant interaction