We used interconnected porous calcium hydroxyapatite ceramic to bridge a rabbit ulnar defect. Two weeks after inducing the defect we percutaneously injected rabbit bone marrow-derived mesenchymal stromal cells labelled with ferumoxide. The contribution of an external magnetic targeting system to attract these cells into the ceramic and their effect on subsequent bone formation were evaluated.

This technique significantly facilitated the infiltration of ferumoxide-labelled cells into ceramic and significantly contributed to the enhancement of bone formation even in the chronic phase. As such, it is potentially of clinical use to treat fractures, bone defects, delayed union and nonunion.

Non-linear methods in statistical shape analysis have become increasingly important in orthopedic research as they allow for more accurate and robust analysis of complex shape data such as articulated joints, bony defects and cartilage loss. These methods involve the use of non-linear transformations to describe shapes, rather than the traditional linear approaches, and have been shown to improve the precision and sensitivity of shape analysis in a variety of applications. In orthopedic research, non-linear methods have been used to study a range of topics, including the analysis of bone shape and structure in relation to osteoarthritis, the assessment of joint deformities and their impact on joint function, and the prediction of patient outcomes following surgical interventions. Overall, the use of non-linear methods in statistical shape analysis has the potential to advance our understanding of the relationship between shape and function in the musculoskeletal system and improve the diagnosis and treatment of orthopedic conditions

Spinal diseases such as unstable fractures, infections, primary or secondary tumors or deformities require surgical stabilization with implants. The long-term success of this treatment is only ensured by a solid bony fusion. The size of the bony defect, the often poor bone quality and metabolic diseases increase the risk of non-union and make the case a great burden for the patient and a challenge for the surgeon. The goal of spinal fusion can only be achieved if the implants used offer sufficient mechanical stability and the local biological regeneration potential is large enough to form sufficient bone. The lecture will present challenging clinical cases. In addition, implant materials and new surgical techniques are discussed. Local therapeutic effects are achieved through the release of osteopromotive or anti-resorbtive drugs, growth factors and antibiotics. By influencing biological pathways, basic orthopedic research has strong potential to further positively change future spinal surgery

Abstract. Approximately 20% of primary and revision Total Knee Arthroplasty (TKA) patients require multiple revisions, which are associated with poor survivorship, with worsening outcomes for subsequent revisions. For revision surgery, either endoprosthetic replacements or metaphyseal sleeves can be used for the repair, however, in cases of severe defects that are deemed “too severe” for reconstruction, endoprosthetic replacement of the affected area is recommended. However, endoprosthetic replacements have been associated with high complication rates (high incidence rates of prosthetic joint infection), while metaphyseal sleeves have a more acceptable complication profile and are therefore preferred. Despite this, no guidance exists as to the maximal limit of bone loss, which is acceptable for the use of metaphyseal sleeves to ensure sufficient axial and rotational stability. Therefore, this study assessed the effect of increasing bone loss on the primary stability of the metaphyseal sleeve in the proximal tibia to determine the maximal bone loss that retains axial and rotational stability comparable to a no defect control. Methods. to determine the pattern of bone loss and the average defect size that corresponds to the clinically defined defect sizes of small, medium and large defects, a series of pre-operative x-rays of patients with who underwent revision TKA were retrospectively analysed. Ten tibiae sawbones were used for the experiment. To prepare the bones, the joint surface was resected the typical resection depth required during a primary TKA (10mm). Each tibia was secured distally in a metal pot with perpendicular screws to ensure rotational and axial fixation to the testing machine. Based on X-ray findings, a fine guide wire was placed 5mm below the cut joint surface in the most medial region of the plateau. Core drills (15mm, 25mm and 35mm) corresponding to small, medium and large defects were passed over the guide wire allowing to act at the centre point, before the bone defect was created. The test was carried out on a control specimen with no defect, and subsequently on a Sawbone with a small, medium or large defect. Sleeves were inserted using the published operative technique, by trained individual using standard instruments supplied by the manufacturers. Standard axial pull-out (0 – 10mm) force and torque (0 – 30°) tests were carried out, recording the force (N) vs. displacement (mm) curves. Results. A circular defect pattern was identified across all defects, with the centre of the defect located 5mm below the medial tibial base plate, and as medial as possible. Unlike with large defects, small and medium sized defects reduced the pull-out force and torque at the bone-implant interface, however, these reductions were not statistically significant when compared to no bony defect. Conclusions. This experimental study demonstrated that up to 35mm radial defects may be an acceptable “critical limit” for bone loss below which metaphyseal sleeve use may still be appropriate. Further clinical assessment may help to confirm the findings of this experimental study. This study is the first in the literature to aim to quantify “critical bone loss” limit in the tibia for revision knee arthroplasty. Declaration of Interest. (a) fully declare any financial or other potential conflict of interest

Latarjet procedure (transfer of coracoid process to the anterior glenoid rim) has been widely used for severe anterior shoulder instability. The purpose of the present study was to investigate the intraarticular stress distribution after this procedure to clarify the pathomechanism of its postoperative complications. CT-DICOM data of the contralateral healthy shoulder in 10 patients with unilateral anterior shoulder instability (9 males and 1 female, age: 17–49) was used for the present study. Three-dimensional finite element models of the glenohumeral joint was developed using software, Mechanical Finder (RCCM, Japan). In each shoulder, a 25% bony defect was created in the anterior glenoid cavity, where coracoid process was transferred using two half-threaded screws. The arm position was determined as 0-degree and 90-degree abduction. While medial margin of the scapula was completely constrained, a standard compressive load (50 N) toward the centre of the glenoid was applied to the lateral wall of the greater tuberosity. A tensile load (20N) was also applied to the tip of coracoid process along the direction of conjoint tendon. Then, elastic analysis was performed, and the distribution pattern of Drucker-Prager equivalent stress was investigated in each model. The proximal half of the coracoid represented significantly lower equivalent stress than the distal half (p < 0.05). In particular, the lowest mean equivalent stress was seen in its proximal-medial-superficial part. On the other hand, a high stress concentration newly appeared in the antero-inferior aspect of the humeral head exactly on the site of coracoid bone graft. We assumed that the reduction of mean equivalent stress in the proximal half of the coracoid was caused by the stress shielding, which may constitute one of the pathogenetic factors of its osteolysis. A high stress concentration in the humeral head may eventually lead shoulder joint to osteoarthritis

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

Since the development of biomimetic and ceramic bone reconstructive in the early 1970, these specialised bioreactors intended for bone or cartilage regeneration have come a long way in trying to design an alternative procedure other than autogenous bone grafting. However, all known biomaterials still fall short of inducing substantial bone formation in vitro or in vivo, especially when treating large bony defects. As such there is a necessity to develop novel bone-reconstructive biomaterials that can more appropriately be utilised and can induce substantial more bone formation than current scaffolds. Using the rapid prototyping technique (Friedrich-Baur BioMed Center, Bayreuth, Germany) to develop new and improved hydroxyapatite/β-tricalcium phosphate devices, which can be predesigned to any outer shape with controlled pore structure and exhibit a unique intrinsic porosity <150µm due to the 3D-printing process to fit any skeletal bone loss site, the aim of our laboratories was to test the osteoinductive capacity of these new bioreactors in an in vitro culture system utilising adipose-derived stem cells (ADSCs). Immunofluorescent staining revealed that beside the standard surface protein expression patterns typical for ADSCs, the cells also produced osteoblast specific proteins, specifically osteocalcin, osteopontin and dentin matrix acidic phosphoprotein 1. ADSCs seeded on the surface of the biomimetic scaffolds showed constant proliferation, maintained viability and differentiation throughout the scaffold, including the small intrinsic pores. Subsequent, qRT-PCR also revealed that alkaline phosphatase and osteocalcin expression was significantly increased upon addition of osteogenic medium but even more so when human recombinant morphogenetic protein 2 (hBMP-2) was included. Immunofluorescent data of protein expression was consistent with qRT-PCR data. Taken into account with previous results by our laboratories in respect to adipose tissue as a viable inductive medium that can form substantial new bone formation in vivo the present results demonstrated that the investigated bioceramic devices possess the necessary capacity that could, together with adipose tissue, provide the next leap necessary to finally and decisively induce substantial or total new bone formation in clinical bone defects of humans

The treatment of bony defects of the tibia at the time of revision total knee replacement is controversial. The place of compacted morsellised bone graft is becoming established, particularly in contained defects. It has previously been shown that the initial stability of impaction-grafted trays in the contained defects is equivalent to that of an uncemented primary knee replacement. However, there is little biomechanical evidence on which to base a decision in the treatment of uncontained defects. We undertook a laboratory-based biomechanical study comparing three methods of graft containment in segmental medial tibial defects and compared them with the use of a modular metal augment to bypass the defect. Using resin models of the proximal tibia with medial defects representing either 46% or 65% of the medial cortical rim, repair of the defect was accomplished using mesh, cement or a novel bag technique, after which impaction bone grafting was used to fill the contained defects and a tibial component was cemented in place. As a control, a cemented tibial component with modular metal augments was used in identical defects. All specimens were submitted to cyclical mechanical loading, during which cyclical and permanent tray displacement were determined. The results showed satisfactory stability with all the techniques except the bone bag method. Using metal augments gave the highest initial stability, but obviously lacked any potential for bone restoration

Summary. A specialised 3D- printed scaffold, combined with fillers and bioactive molecules, can be designed and characterised to demonstrate the efficacy of synthetic, off-the-shelf and custom fabricated scaffolds for the repair of long bone defects. Introduction. Using specialised three-dimensional (3-D) printing technology, combined with fillers and bioactive molecules, 3-D scaffolds for bone repair of sizable defects can be manufactured with a level of design customization that other methods lack. Hydroxyapatite (HA)/Beta-Tri-Calcium Phosphate (β -TCP) scaffold components may be created that provide mechanical strength, guide osseo- conduction and integration, and remodel over time. Additionally, research suggests that bone morphogenic protein (BMP) stimulates growth and differentiation of new bone. Therefore, we hypothesise that with the addition of BMP, HA- β -TCP scaffolds will show improved regeneration of bone over critical sized bone defects in an in vivo model. Patients & Methods. Scaffolds were implanted in six New Zealand White rabbits with a 10mm radial defect for 2 and 8 weeks. The scaffolds, made from 15% HA: 85% β-TCP, were designed using ROBOCAD design software and fabricated using a 3-D printing Robocast machine. Scaffolds were sintered at 1100°C for 4 hours with a final composition of 5% HA: ∼95% β-TCP. Micro-CT, histological analysis, and nanoindentation were conducted to determine the degree of new bone formation and remodeling. Results. Reconstructed microCT images show increased bone formation, remodeling, and integration in HA/ β -TCP-BMP scaffolds compared to virgin HA/ β -TCP scaffolds. Histological analysis showed increased bone formation but decreased osteoconduction in HA/ β -TCP-BMP scaffolds. Nanoindentation showed no effect of BMP on hardness nor elastic modulus of bone formed on the scaffolds. Discussion/Conclusions. HA/ β -TCP scaffolds with/without BMP are highly biocompatible and can successfully augment and accelerate the regeneration and remodeling of bone in critically sized long bone defects in a rabbit model. However, the data in this study show both improvement and detriment with the addition of BMP. Therefore, further studies must be performed. Ideally, eventual translation of this research to humans would eliminate the need for allograft and/or autograft in large bony defects and allow for a customizable 3D scaffold material relative to patient needs

We studied peridural fibrosis in 16 dogs after laminectomies at the L2, L4 and L6 levels. They received either a free fat graft, a biodegradable mechanical barrier (polyethylene oxide (PEO)/polybutylene terephthalate (PBT) copolymer), or no treatment. The animals were killed after 4, 12, 26 and 52 weeks. Histomorphometry showed extensive and consistent peridural fibrosis in control and PEO/PBT groups. Fat grafts produced significantly less fibrous tissue, but the presence of the fat graft in the bony defect prevented closure. Degradation of the PEO/PBT barrier resulted in the formation of more fibrous tissue. We conclude that up to one year a free fat graft is effective in reducing the amount of peridural scarring

The treatment of large bony defects by callus distraction is well accepted, but the duration of treatment is long and the rate of complications increases accordingly. We have examined the effect of the stiffness of the axial fixator on reducing the time for maturation of callus. We created a mid-diaphyseal defect of 15 mm in the metatarsal bone in sheep and stabilised it with a ring fixator. After four days a bony segment was transported for 16 days at 1 mm per day. After 64 days the animals were divided into four groups, three with axial interfragmentary movement (IFM) of 0.5, 1.2 and 3.0 mm, respectively, and a control group. The 3.0 mm IFM group had the smallest bone density (p = 0.001) and area of callus and the largest IFM after 12 weeks; it also had typical clinical signs of hypertrophic nonunion. The most rapid stiffening of the callus was in the 0.5 mm group which had the smallest IFM (p = 0.04) after 12 weeks and radiological signs of bridging of the defect. These results indicate that suitable dynamic axial stimulation can enhance maturation of distraction callus when the initial amplitude is small, but that a large IFM can lead to delayed union

Summary Statement. Supercritical fluid (SCF) sterilization produces clean and osteoconductive allograft bone capable of healing a critical-sised bony defect. SCF treated graft induces an increased anabolic response and decreased catabolic reponse compared to gamma irradiated graft. Introduction. Clinically, allogeneic bone graft is used extensively because it avoids the donor site morbidity associated with autograft. However, there are concerns over the optimal sterilization method to eliminate immunological risks whilst maintaining the biological efficacy of the graft. This study compared the effect of Supercritical fluid (SCF) sterilization and gamma irradiation on the osteoconductivity of allograft bone in a bilateral critical-sised defect rabbit model. Methods. Cortical-cancellous allograft bone was milled, defatted and terminally sterilised with either gamma irradiation at 25kGy or SCF treatment. The graft was then implanted bilaterally into a critical-sised metaphyseal defect in 10 New Zealand White rabbits (n=5 sites per time point per group). Osteoconductivity was evaluated at 2 and 4 weeks to measure the early inflammatory response and early new bone formation respectively, using X-ray, CT, and both qualitative and quantitative histology and immunohistochemistry (Alkaline Phosphatase and Cathepsin-K). Results. Both grafts were well tolerated and osteoconductive. At 2 weeks, there were significant reductions in bone volume and density in the gamma irradiated graft compared to the SCF treated graft as measured by CT. Inside the defect this corresponded with a greater inflammatory response in the gamma irradiated graft, with a less organised fibrous tissue infiltration and mild granuloma reaction. Conversely, the SCF group had a highly organised and densely packed fibrous tissue infiltration around the allograft chips. Immunohistochemistry results supported these findings with an up-regulation in the expression and distribution of Cathepsin-K in the gamma irradiation group; while Alkaline Phosphatase expression was higher in the SCF group. At 4 weeks, resorptive behavior predominated in both groups. Radiographic and CT results detected no significant difference between groups. Histology at 4 weeks showed larger bone chips were undergoing substantial remodeling with areas of simultaneous osteoclastic resorption and osteoblastic new bone formation. Smaller allograft chips and areas of new bone formation were infiltrated by fibrous tissue and undergoing osteoclastic resorption. Quantitative immunohistochemistry showed an up-regulation of Cathepsin-K expression in both groups from 2 to 4 weeks. At both time points Cathepsin-K expression was higher in the gamma irradiated graft compared to the SCF group. This was greatest at 2 weeks where there was a substantial 82% increase in expression which was reduced to a 38% discrepancy at 4 weeks. Alkaline Phosphatase expression was greater in the SCF group at both time-points. Discussion/Conclusion. Allograft bone sterilised with either gamma irradiation or SCF treatment was osteoconductive and capable of healing a critical-sised defect in a rabbit. Gamma irradiated allografts elicited an acute inflammatory reaction when implanted which increased the amount graft resorption compared to the SCF treated bone. Increased osteoclastic resorption may be a concern for structural graft applications leaving the graft more susceptible to premature failure. SCF sterilization produced a clean, highly biocompatible graft with increased anabolic activity compared to gamma irradiation which may facilitate earlier healing clinically. These results suggest that SCF sterilization has considerable expediency for allograft processing and may facilitate more optimal extraction of the inherent properties of the graft compared to current practices

Objectives

All-suture anchors are increasingly used in rotator cuff repair procedures. Potential benefits include decreased bone damage. However, there is limited published evidence for the relative strength of fixation for all-suture anchors compared with traditional anchors.

External fixation of distal tibial fractures is often associated with delayed union. We have investigated whether union can be enhanced by using recombinant bone morphogenetic protein-7 (rhBMP-7).

Osteoinduction with rhBMP-7 and bovine collagen was used in 20 patients with distal tibial fractures which had been treated by external fixation (BMP group). Healing of the fracture was compared with that of 20 matched patients in whom treatment was similar except that rhBMP-7 was not used.

Significantly more fractures had healed by 16 (p = 0.039) and 20 weeks (p = 0.022) in the BMP group compared with the matched group. The mean time to union (p = 0.002), the duration of absence from work (p = 0.018) and the time for which external fixation was required (p = 0.037) were significantly shorter in the BMP group than in the matched group. Secondary intervention due to delayed healing was required in two patients in the BMP group and seven in the matched group.

RhBMP-7 can enhance the union of distal tibial fractures treated by external fixation.

Objectives

The major problem with repair of an articular cartilage injury is the extensive difference in the structure and function of regenerated, compared with normal cartilage. Our work investigates the feasibility of repairing articular osteochondral defects in the canine knee joint using a composite lamellar scaffold of nano-ß-tricalcium phosphate (ß-TCP)/collagen (col) I and II with bone marrow stromal stem cells (BMSCs) and assesses its biological compatibility.

Objectives

Acetabular retractors have been implicated in damage to the femoral and obturator nerves during total hip replacement. The aim of this study was to determine the anatomical relationship between retractor placement and these nerves.

The aim of this study was to determine the effectiveness of antibiotic-impregnated implants in the prevention of bone infection. We used a model of contaminated fracture in goats to evaluate four treatment groups: no treatment, hand-made tobramycin-impregnated polymethylmethacrylate beads, commercially-available tobramycin-impregnated calcium sulphate pellets and commercially-available tobramycin-impregnated polymethylmethacrylate beads. Three weeks after intraosseous inoculation with streptomycin-resistant Staphylococcus aureus tissue cultures showed no evidence of infection in any of the antibiotic-treated groups. All of the cultures were positive in the untreated group. These results show that effective local antibiotic delivery can be obtained with both commercially-available products and with hand-made polymethylmethacrylate beads. The calcium sulphate pellets have the advantage of being bioabsorbable, thereby obviating the need for a second procedure to remove them.

This study investigated the quality and quantity of healing of a bone defect following intramedullary reaming undertaken by two fundamentally different systems; conventional, using non-irrigated, multiple passes; or suction/irrigation, using one pass. The result of a measured re-implantation of the product of reaming was examined in one additional group. We used 24 Swiss mountain sheep with a mean tibial medullary canal diameter between 8 mm and 9 mm. An 8 mm ‘napkin ring’ defect was created at the mid-diaphysis. The wound was either surgically closed or occluded. The medullary cavity was then reamed to 11 mm. The Reamer/Irrigator/Aspirator (RIA) System was used for the reaming procedure in groups A (RIA and autofilling) and B (RIA, collected reamings filled up), whereas reaming in group C (Synream and autofilling) was performed with the Synream System. The defect was allowed to auto-fill with reamings in groups A and C, but in group B, the defect was surgically filled with collected reamings. The tibia was then stabilised with a solid locking Unreamed Humerus Nail (UHN), 9.5 mm in diameter. The animals were killed after six weeks. After the implants were removed, measurements were taken to assess the stiffness, strength and callus formation at the site of the defect.

There was no significant difference between healing after conventional reaming or suction/irrigation reaming. A significant improvement in the quality of the callus was demonstrated by surgically placing captured reamings into the defect using a graft harvesting system attached to the aspirator device. This was confirmed by biomechanical testing of stiffness and strength. This study suggests it could be beneficial to fill cortical defects with reaming particles in clinical practice, if feasible.

Ciprofloxacin hydrochloride-loaded microspheres were prepared by a spray-drying method using pectin and chitosan. The effects of different polymers and drug ratios were investigated.

The most appropriate carriers were selected by in vitro testing. A rat methicillin-resistant Staphylococcus aureus osteomyelitis model was used to evaluate the effects of the loaded microspheres.

The drug was released rapidly from the pectin carrier but this was more sustained in the chitosan formulation.

Chitosan microspheres loaded with ciprofloxacin hydrochloride were more effective for the treatment of osteomyelitis than equivalent intramuscular antibiotics.