Objectives. We sought to determine if a durable bilayer implant composed of trabecular metal with autologous periosteum on top would be suitable to reconstitute large osteochondral defects. This design would allow for secure implant fixation, subsequent integration and remodeling. Materials and Methods. Adult sheep were randomly assigned to one of three groups (n = 8/group): 1. trabecular metal/periosteal graft (TMPG), 2. trabecular metal (TM), 3. empty defect (ED). Cartilage and bone healing were assessed macroscopically, biochemically (type II collagen, sulfated glycosaminoglycan (sGAG) and double-stranded DNA (dsDNA) content) and histologically. Results. At 16 weeks post-operatively, histological scores amongst treatment groups were not statistically different (TMPG: overall 12.7, cartilage 8.6, bone 4.1; TM: overall 14.2, cartilage 9.5, bone 4.9; ED: overall 13.6, cartilage 9.1, bone 4.5). Metal scaffolds were incorporated into the surrounding bone, both in TM and TMPG. The sGAG yield was lower in the neo-cartilage regions compared with the articular cartilage (AC) controls (TMPG 20.8/AC 39.5, TM 25.6/AC 33.3, ED 32.2/AC 40.2 µg sGAG/1 mg respectively), with statistical significance being achieved for the TMPG group (p < 0.05). Hypercellularity of the neo-cartilage was found in TM and ED, as the dsDNA content was significantly higher (p < 0.05) compared with contralateral AC controls (TM 126.7/AC 71.1, ED 99.3/AC 62.8 ng dsDNA/1 mg). The highest type II collagen content was found in neo-cartilage after TM compared with TMPG and ED (TM 60%/TMPG 40%/ED 39%). Inter-treatment differences were not significant. Conclusions. TM is a highly suitable material for the reconstitution of osseous defects. TM enables excellent bony ingrowth and fast integration. However, combined with autologous periosteum, such a biocomposite failed to promote satisfactory neo-cartilage formation. Cite this article: E. H. Mrosek, H-W. Chung, J. S. Fitzsimmons, S. W. O’Driscoll, G. G. Reinholz, J. C. Schagemann. Porous tantalum biocomposites for osteochondral defect repair: A follow-up study in a sheep model. Bone Joint J 2016;5:403–411. DOI: 10.1302/2046-3758.59.BJR-2016-0070.R1

An experimental sheep model was used for impaction allografting of 12 hemiarthroplasty femoral components placed into two equal-sized groups. In group 1, a 50:50 mixture of ApaPore hydroxyapatite bone-graft substitute and allograft was used. In group 2, ApaPore and allograft were mixed in a 90:10 ratio. Both groups were killed at six months. Ground reaction force results demonstrated no significant differences (p > 0.05) between the two groups at 8, 16 and 24 weeks post-operatively, and all animals remained active. The mean bone turnover rates were significantly greater in group 1, at 0.00206 mm/day, compared to group 2 at 0.0013 mm/day (p < 0.05). The results for the area of new bone formation demonstrated no significant differences (p > 0.05) between the two groups. No significant differences were found between the two groups in thickness of the cement mantle (p > 0.05) and percentage ApaPore-bone contact (p > 0.05). The results of this animal study demonstrated that a mixture of ApaPore allograft in a 90:10 ratio was comparable to using a 50:50 mixture

The aim of this randomised, controlled in vivo study in an ovine model was to investigate the effect of cylic pneumatic pressure on fracture healing. We performed a transverse osteotomy of the right radius in 37 sheep. They were randomised to a control group or a treatment group where they received cyclic loading of the osteotomy by the application of a pressure cuff around the muscles of the proximal forelimb. Sheep from both groups were killed at four or six weeks. Radiography, ultrasonography, biomechanical testing and histomorphometry were used to assess the differences between the groups. The area of periosteal callus, peak torsional strength, fracture stiffness, energy absorbed over the first 10° of torsion and histomorphometric analysis all showed that the osteotomies treated with the cyclic pneumatic pressure at four weeks were not significantly different from the control osteotomies at six weeks

We released the infraspinatus tendons of six sheep, allowed retraction of the musculotendinous unit over a period of 40 weeks and then performed a repair. We studied retraction of the musculotendinous unit 35 weeks later using CT, MRI and macroscopic dissection. The tendon was retracted by a mean of 4.7 cm (3.8 to 5.1) 40 weeks after release and remained at a mean of 4.2 cm (3.3 to 4.7) 35 weeks after the repair. Retraction of the muscle was only a mean of 2.7 cm (2.0 to 3.3) and 1.7 cm (1.1 to 2.2) respectively at these two points. Thus, the musculotendinous junction had shifted distally by a mean of 2.5 cm (2.0 to 2.8) relative to the tendon. Sheep muscle showed an ability to compensate for approximately 60% of the tendon retraction in a hitherto unknown fashion. Such retraction may not be a quantitatively reliable indicator of retraction of the muscle and may overestimate the need for elongation of the musculotendinous unit during repair

Objectives. To compare the therapeutic potential of tissue-engineered constructs (TECs) combining mesenchymal stem cells (MSCs) and coral granules from either Acropora or Porites to repair large bone defects. Materials and Methods. Bone marrow-derived, autologous MSCs were seeded on Acropora or Porites coral granules in a perfusion bioreactor. Acropora-TECs (n = 7), Porites-TECs (n = 6) and bone autografts (n = 2) were then implanted into 25 mm long metatarsal diaphyseal defects in sheep. Bimonthly radiographic follow-up was completed until killing four months post-operatively. Explants were subsequently processed for microCT and histology to assess bone formation and coral bioresorption. Statistical analyses comprised Mann-Whitney, t-test and Kruskal–Wallis tests. Data were expressed as mean and standard deviation. Results. A two-fold increaseof newly formed bone volume was observed for Acropora-TECs when compared with Porites-TECs (14 . sd. 1089 mm. 3. versus 782 . sd. 507 mm. 3. ; p = 0.09). Bone union was consistent with autograft (1960 . sd. 518 mm. 3. ). The kinetics of bioresorption and bioresorption rates at four months were different for Acropora-TECs and Porites-TECs (81% . sd. 5% versus 94% . sd. 6%; p = 0.04). In comparing the defects that healed with those that did not, we observed that, when major bioresorption of coral at two months occurs and a scaffold material bioresorption rate superior to 90% at four months is achieved, bone nonunion consistently occurred using coral-based TECs. Discussion. Bone regeneration in critical-size defects could be obtained with full bioresorption of the scaffold using coral-based TECs in a large animal model. The superior performance of Acropora-TECs brings us closer to a clinical application, probably because of more suitable bioresorption kinetics. However, nonunion still occurred in nearly half of the bone defects. Cite this article: A. Decambron, M. Manassero, M. Bensidhoum, B. Lecuelle, D. Logeart-Avramoglou, H. Petite, V. Viateau. A comparative study of tissue-engineered constructs from Acropora and Porites coral in a large animal bone defect model. Bone Joint Res 2017;6:208–215. DOI: 10.1302/2046-3758.64.BJR-2016-0236.R1

This study investigates the use of porous biphasic ceramics as graft extenders in impaction grafting of the femur during revision hip surgery. Impaction grafting of the femur was performed in four groups of sheep. Group one received pure allograft, group two 50% allograft and 50% BoneSave, group three 50% allograft and 50% BoneSave type 2 and group four 10% allograft and 90% BoneSave as the graft material. Function was assessed using an index of pre- and post-operative peak vertical ground reaction force ratios. Changes in bone mineral density were measured by dual energy X ray absorptiometry (DEXA) scanning. Loosening and subsidence were assessed radiographically and by histological examination of the explanted specimens. There was no statistically significant difference between the four groups after 18 months of unrestricted functional loading for all outcome measures

Allograft bone is widely used in orthopaedic surgery, but peri-operative infection of the graft remains a common and disastrous complication. The efficacy of systemic prophylactic antibiotics is unproven, and since the graft is avascular it is likely that levels of antibiotic in the graft are low. Using an electrical potential to accelerate diffusion of antibiotics into allograft bone, high levels were achieved in specimens of both sheep and human allograft. In human bone these ranged from 187.1 mg/kg in endosteal (. sd. 15.7) to 124.6 (. sd. 46.2) in periosteal bone for gentamicin and 31.9 (. sd. 8.9) in endosteal and 2.9 (. sd. 1.1) in periosteal bone for flucloxacillin. The antibiotics remained active against bacteria in vitro after iontophoresis and continued to elute from the allograft for up to two weeks. Structural allograft can be supplemented directly with antibiotics using iontophoresis. The technique is simple and inexpensive and offers a potential means of reducing the rate of peri-operative infection in allograft surgery. Iontophoresis into allograft bone may also be applicable to other therapeutic compounds

An understanding of the remodelling of tendon is crucial for the development of scientific methods of treatment and rehabilitation. This study tested the hypothesis that tendon adapts structurally in response to changes in functional loading. A novel model allowed manipulation of the mechanical environment of the patellar tendon in the presence of normal joint movement via the application of an adjustable external fixator mechanism between the patella and the tibia in sheep, while avoiding exposure of the patellar tendon itself. Stress shielding caused a significant reduction in the structural and material properties of stiffness (79%), ultimate load (69%), energy absorbed (61%), elastic modulus (76%) and ultimate stress (72%) of the tendon compared with controls. Compared with the material properties the structural properties exhibited better recovery after re-stressing with stiffness 97%, ultimate load 92%, energy absorbed 96%, elastic modulus 79% and ultimate stress 80%. The cross-sectional area of the re-stressed tendons was significantly greater than that of stress-shielded tendons. The remodelling phenomena exhibited in this study are consistent with a putative feedback mechanism under strain control. This study provides a basis from which to explore the interactions of tendon remodelling and mechanical environment

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

Carbonate-substituted hydroxyapatite (CHA) is more osteoconductive and more resorbable than hydroxyapatite (HA), but the underlying mode of its action is unclear. We hypothesised that increased resorption of the ceramic by osteoclasts might subsequently upregulate osteoblasts by a coupling mechanism, and sought to test this in a large animal model. Defects were created in both the lateral femoral condyles of 12 adult sheep. Six were implanted with CHA granules bilaterally, and six with HA. Six of the animals in each group received the bisphosphonate zoledronate (0.05 mg/kg), which inhibits the function of osteoclasts, intra-operatively. After six weeks bony ingrowth was greater in the CHA implants than in HA, but not in the animals given zoledronate. Functional osteoclasts are necessary for the enhanced osteoconduction seen in CHA compared with HA

Perilesional changes of chronic focal osteochondral defects were assessed in the knees of 23 sheep. An osteochondral defect was created in the main load-bearing region of the medial condyle of the knees in a controlled, standardised manner. The perilesional cartilage was evaluated macroscopically and biopsies were taken at the time of production of the defect (T0), during a second operation one month later (T1), and after killing animals at three (T3; n = 8), four (T4; n = 8), and seven (T7; n = 8) months. All the samples were histologically assessed by the International Cartilage Repair Society grading system and Mankin histological scores. Biopsies were taken from human patients (n = 10) with chronic articular cartilage lesions and compared with the ovine specimens. The ovine perilesional cartilage presented with macroscopic and histological signs of degeneration. At T1 the International Cartilage Repair Society ‘Subchondral Bone’ score decreased from a mean of 3.0 (. sd. 0) to a mean of 1.9 (. sd. 0.3) and the ‘Matrix’ score from a mean of 3.0 (. sd. 0) to a mean of 2.5 (. sd. 0.5). This progressed further at T3, with the International Cartilage Repair Society ‘Surface’ grading, the ‘Matrix’ grading, ‘Cell Distribution’ and ‘Cell Viability’ grading further decreasing and the Mankin score rising from a mean of 1.3 (. sd. 1.4) to a mean of 5.1 (. sd. 1.6). Human biopsies achieved Mankin grading of a mean of 4.2 (. sd. 1.6) and were comparable with the ovine histology at T1 and T3. The perilesional cartilage in the animal model became chronic at one month and its histological appearance may be considered comparable with that seen in human osteochondral defects after trauma

The ability to predict load-bearing capacity during the consolidation phase in distraction osteogenesis by non-invasive means would represent a significant advance in the management of patients undergoing such treatment. Measurements of stiffness have been suggested as a promising tool for this purpose. Although the multidimensional characteristics of bone loading in compression, bending and torsion are apparent, most previous experiments have analysed only the relationship between maximum load-bearing capacity and a single type of stiffness. We have studied how compressive, bending and torsional stiffness are related to the torsional load-bearing capacity of healing callus using a common set of samples of bone regenerate from 26 sheep treated by tibial distraction osteogenesis. Our findings showed that measurements of torsional, bending and compressive stiffness were all suitable as predictors of the load-bearing capacity of healing callus. Measurements of torsional stiffness performed slightly better than those of compressive and bending stiffness

We examined the radiographs from a prospective clinical study of fixation by pedicle screws and those from an experimental study in a sheep model. In the clinical study, instruments were removed from 21 patients after implantation for 11 to 16 months and the extraction torques of the screws were recorded. A structured protocol was used for the radiological examinations. In the experimental study, loaded pedicle screw instrumentations were implanted in the sheep for six or 12 weeks. After radiological examination the pull-out resistance and the histological characteristics were studied. In the clinical study, all screws with radiolucent zones had a significantly reduced mean extraction torque compared with screws without radiolucent zones (16 ± 10 Ncm v 403 ± 220 Ncm; p < 0.0001). In the experimental study the mean maximum pull-out resistance for the screws with radiolucent zones was significantly lower than for those with no radiolucency (243 ± 156 N v 2214 ± 578 N; p = 0.0006) and the mean bone-to-screw contact was reduced for screws with zones compared with those without zones (8 ± 9% v 55 ± 29%; p = 0.0002). Our findings showed that all screws with radiolucent zones had low extraction torques or low pull-out resistance. A radiolucent zone is a good indicator of loosening of a pedicle screw

Foreign-body reaction to polyglycolide (PGA) implants has been described in man. Many animal experiments have verified the mechanical properties of fixation devices made from PGA, but a significant foreign-body reaction has not been described. We studied the effect of PGA rods in 12 sheep with standardized osteochondral fractures of the medial femoral condyle fixed with uncoloured, self-reinforced PGA rods (Biofix). Radiographs were taken at intervals ranging from two weeks to two years, and the sheep were killed at intervals ranging from six to 24 months. All knees were examined histologically. Eleven of the 12 fractures healed radiologically and histologically. Moderate to severe osteolysis was seen at four to six weeks with maximum changes at 12 weeks in ten animals. Six knees showed fistula-like connections between the implant site and the joint space. Three developed synovitis, one with inflammatory changes involving the whole cartilage and one with destruction of the medial condyle. Although in our study osteochondral fractures fixed with PGA rods healed reliably, there were frequent, significant foreign-body reactions. Caution is needed when considering the use of PGA fixation devices in vulnerable regions such as the knee

Our aim was to examine the potential of autologous perichondral tissue to form a meniscal replacement. In 18 mature sheep we performed a complete medial meniscectomy. The animals were then divided into two groups: 12 had a meniscal replacement using strips of autologous perichondral tissue explanted from the lower rib (group G) and six (group C) served as a control group without a meniscal replacement. In all animals restriction from weight-bearing was achieved by means of transection and partial resection of tendo Achillis. Six animals (four from group G and two from group C) were each killed at 3, 6 and 12 months. The grafts and the underlying articular cartilage were removed and studied by gross macroscopic examination, light microscopy, SEM, polarised light examination, and by biomechanical tests. In all the transplanted animals a new perichondral meniscus developed. After three months the transplants resembled normal menisci in size and thickness, while in the control animals only small rims of spontaneously grown tissue were seen. Microscopically, the perichondral menisci showed a normal orientation of collagen fibres and normal cellular characteristics, but in the central region, areas of calcification disturbed the regular tissue differentiation. Healing tissue in control animals lacked the normal fibre orientation and cellularity. SEM of perichondral menisci showed surface characteristics similar to those of normal sheep menisci without fissures and lacerations; the control specimens had these defects. The femoral and tibial cartilage in contact with the new menisci had normal surface characteristics apart from one animal with slight surface irregularities. Control animals showed superficial lesions after three months which increased at six to 12 months postoperatively. Microangiography of the newly grown tissue demonstrated a less intense vascularisation after three months when compared with normal menisci. The failure stress and tensile modulus of perichondral menisci were significantly lower than those of normal contralateral menisci, and spontaneously regenerated tissue in meniscectomised animals had even lower values. There were no significant differences in values between newly grown perichondral menisci and spontaneously grown tissue

We studied the effect of the surface finish of the stem on the transfer of load in the proximal femur in a sheep model of cemented hip arthroplasty. Strain-gauge analysis and corresponding finite-element (FE) analysis were performed to assess the effect of friction and creep at the cement-stem interface. No difference was seen between the matt and polished stems. FE analysis showed that the effects of cement creep and friction at the stem-cement interface on femoral strain were small compared with the effect of inserting a cemented stem

It is well recognised that meniscal tears situated within the inner, avascular region do not heal. We investigated the potential effect of insulin-like growth factor-I (IGF-I) in promoting regeneration of meniscal tissue in the inner, middle and outer zones of the meniscus. Sheep menisci were harvested and monolayer cell cultures prepared. Various concentrations of IGF-I were used in the presence or absence of 10% fetal calf serum (FCS). We measured the uptake of radioactive thymidine, sulphur, and proline to assess cell proliferation and formation of extracellular matrix (ECM). IGF-I, in the presence or absence of FCS, increased the formation of DNA and ECM in all meniscal zones. However, the response of the cells from the avascular zone was greater than that from the vascular zone. Our findings indicate that fibrochondrocytes cultured from avascular meniscal tissue have the ability to regenerate when exposed to anabolic cytokines such as IGF-I

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

We aimed to highlight the relationship between age and the architectural properties of trabecular bone, to outline the patterns in which the variations in these properties take place, and to investigate the influence of the architecture on the mechanical properties of trabecular bone in growing animals. We studied 30 lambs in three age groups and 20 sheep in two age groups. Cubes of subchondral bone were cut from the proximal tibia according to a standardised protocol. They were serially sectioned and their architectural properties were determined. Similar cubes were obtained from the identical anatomical position of the contralateral tibia and their compressive mechanical properties measured. The values obtained from the skeletally immature and mature individuals were compared. Multiple regression analyses were performed between the architectural and the mechanical properties. The bone volume fraction, the mean trabecular volume, the architectural and the mechanical anisotropy, the elastic modulus, the bone strength, the energy absorption to failure, and the elastic energy correlated positively with increasing age whereas the connectivity density, the bone surface density, the ultimate strain, the absorption of viscoelastic energy and the relative loss of energy correlated inversely. The values of all variables were significantly different in the skeletally mature and immature groups. We determined the patterns in which the variations took place. The bone volume fraction of the trabecular bone tissue was found to be the major predictor of its compressive mechanical properties. Together with the mean trabecular volume and the bone surface density, it explained 81% of the variations in the compressive elastic modulus of specimens obtained from the contralateral tibiae

Our aim was to determine the relationship between age and the mechanical and physical properties of trabecular bone, to describe the patterns in which the variations in these properties take place, and to investigate the influence of the physical properties on the mechanical characteristics of trabecular bone during growth. We used 30 lambs in three age groups and 20 sheep in two age groups. Cubes of subchondral bone were cut from the proximal tibia according to a standardised protocol. We performed non-destructive compression tests of the specimens in three orthogonal directions and compression tests to failure in the axial direction. The physical properties of the specimens were also determined. The data were correlated with age and compared in skeletally immature and mature animals. Multiple regression analyses were performed between the mechanical and the physical properties. Age correlated positively with elastic modulus, bone strength, energy absorption to failure, elastic energy, mechanical anisotropy ratio, tissue density, apparent density, apparent ash density, and bone mineral content, and inversely with ultimate strain, viscoelastic energy absorption, relative energy loss, the collagen content of bone and the percentage porosity. The values of all variables were significantly different in the skeletally mature and immature groups. The apparent density of trabecular bone tissue was found to be the major predictor of its compressive mechanical properties. Together with the content of bone muscle and bone collagen, the apparent density could explain 84% of the variation in the elastic modulus, whereas only a small portion of the variation in ultimate strain could be explained by the variation in apparent density

Objectives

The treatment of osteoporotic fractures is a major challenge, and the enhancement of healing is critical as a major goal in modern fracture management. Most osteoporotic fractures occur at the metaphyseal bone region but few models exist and the healing is still poorly understood. A systematic review was conducted to identify and analyse the appropriateness of current osteoporotic metaphyseal fracture animal models.

Objectives

Infection of implants is a major problem in elective and trauma surgery. Heating is an effective way to reduce the bacterial load in food preparation, and studies on hyperthermia treatment for cancer have shown that it is possible to heat metal objects with pulsed electromagnetic fields selectively (PEMF), also known as induction heating. We therefore set out to answer the following research question: is non-contact induction heating of metallic implants effective in reducing bacterial load in vitro?

Objectives

In this study, we compared the pain behaviour and osteoarthritis (OA) progression between anterior cruciate ligament transection (ACLT) and osteochondral injury in surgically-induced OA rat models.

This review is aimed at clinicians appraising preclinical trauma studies and researchers investigating compromised bone healing or novel treatments for fractures. It categorises the clinical scenarios of poor healing of fractures and attempts to match them with the appropriate animal models in the literature.

We performed an extensive literature search of animal models of long bone fracture repair/nonunion and grouped the resulting studies according to the clinical scenario they were attempting to reflect; we then scrutinised them for their reliability and accuracy in reproducing that clinical scenario.

Models for normal fracture repair (primary and secondary), delayed union, nonunion (atrophic and hypertrophic), segmental defects and fractures at risk of impaired healing were identified. Their accuracy in reflecting the clinical scenario ranged greatly and the reliability of reproducing the scenario ranged from 100% to 40%.

It is vital to know the limitations and success of each model when considering its application.

Objectives

Implant-related infection is one of the most devastating complications in orthopaedic surgery. Many surface and/or material modifications have been developed in order to minimise this problem; however, most of the in vitro studies did not evaluate bacterial adhesion in the presence of eukaryotic cells, as stated by the ‘race for the surface’ theory. Moreover, the adherence of numerous clinical strains with different initial concentrations has not been studied.

Objectives

This systematic review aimed to assess the in vivo and clinical effect of strontium (Sr)-enriched biomaterials in bone formation and/or remodelling.

Ovine articular chondrocytes were isolated from cartilage biopsy and culture expanded in vitro. Approximately 30 million cells per ml of cultured chondrocytes were incorporated with autologous plasma-derived fibrin to form a three-dimensional construct. Full-thickness punch hole defects were created in the lateral and medial femoral condyles. The defects were implanted with either an autologous ‘chondrocyte-fibrin’ construct (ACFC), autologous chondrocytes (ACI) or fibrin blanks (AF) as controls. Animals were killed after 12 weeks. The gross appearance of the treated defects was inspected and photographed. The repaired tissues were studied histologically and by scanning electron microscopy analysis.

All defects were assessed using the International Cartilage Repair Society (ICRS) classification. Those treated with ACFC, ACI and AF exhibited median scores which correspond to a nearly-normal appearance. On the basis of the modified O’Driscoll histological scoring scale, ACFC implantation significantly enhanced cartilage repair compared to ACI and AF. Using scanning electron microscopy, ACFC and ACI showed characteristic organisation of chondrocytes and matrices, which were relatively similar to the surrounding adjacent cartilage.

Implantation of ACFC resulted in superior hyaline-like cartilage regeneration when compared with ACI. If this result is applicable to humans, a better outcome would be obtained than by using conventional ACI.

The stress response to trauma is the summation of the physiological response to the injury (the ‘first hit’) and by the response to any on-going physiological disturbance or subsequent trauma surgery (the ‘second hit’).

Our animal model was developed in order to allow the study of each of these components of the stress response to major trauma. High-energy, comminuted fracture of the long bones and severe soft-tissue injuries in this model resulted in a significant tropotropic (depressor) cardiovascular response, transcardiac embolism of medullary contents and activation of the coagulation system. Subsequent stabilisation of the fractures using intramedullary nails did not significantly exacerbate any of these responses.

Critical size defects in ovine tibiae, stabilised with intramedullary interlocking nails, were used to assess whether the addition of carboxymethylcellulose to the standard osteogenic protein-1 (OP-1/BMP-7) implant would affect the implant’s efficacy for bone regeneration. The biomaterial carriers were a ‘putty’ carrier of carboxymethylcellulose and bovine-derived type-I collagen (OPP) or the standard with collagen alone (OPC). These two treatments were also compared to “ungrafted” negative controls. Efficacy of regeneration was determined using radiological, biomechanical and histological evaluations after four months of healing. The defects, filled with OPP and OPC, demonstrated radiodense material spanning the defect after one month of healing, with radiographic evidence of recorticalisation and remodelling by two months. The OPP and OPC treatment groups had equivalent structural and material properties that were significantly greater than those in the ungrafted controls. The structural properties of the OPP- and OPC-treated limbs were equivalent to those of the contralateral untreated limb (p > 0.05), yet material properties were inferior (p < 0.05). Histopathology revealed no residual inflammatory response to the biomaterial carriers or OP-1. The OPP- and OPC-treated animals had 60% to 85% lamellar bone within the defect, and less than 25% of the regenerate was composed of fibrous tissue. The defects in the untreated control animals contained less than 40% lamellar bone and more than 60% was fibrous tissue, creating full cortical thickness defects. In our studies carboxymethylcellulose did not adversely affect the capacity of the standard OP-1 implant for regenerating bone.

While the evolution of the bony skeleton of the shoulder girdle is well described, there is little information regarding the soft tissues, in particular of the rotator cuff. We dissected the shoulders of 23 different species and compared the anatomical features of the tendons of the rotator cuff. The alignment and orientation of the collagen fibres of some of the tendons were also examined histologically. The behaviour of the relevant species was studied, with particular reference to the extent and frequency of forward-reaching and overhead activity of the forelimb.

In quadrupedal species, the tendons of supraspinatus, infraspinatus and teres minor were seen to insert into the greater tuberosity of the humerus separately. They therefore did not form a true rotator cuff with blending of the tendons. This was only found in advanced primates and in one unusual species, the tree kangaroo. These findings support the suggestion that the appearance of the rotator cuff in the evolutionary process parallels anatomical adaptation to regular overhead activity and the increased use of the arm away from the sagittal plane.

We have designed a prospective study to evaluate the usefulness of prolonged incubation of cultures from sonicated orthopaedic implants. During the study period 124 implants from 113 patients were processed (22 osteosynthetic implants, 46 hip prostheses, 54 knee prostheses, and two shoulder prostheses). Of these, 70 patients had clinical infection; 32 had received antibiotics at least seven days before removal of the implant. A total of 54 patients had sonicated samples that produced positive cultures (including four patients without infection). All of them were positive in the first seven days of incubation. No differences were found regarding previous antibiotic treatment when analysing colony counts or days of incubation in the case of a positive result. In our experience, extending incubation of the samples to 14 days does not add more positive results for sonicated orthopaedic implants (hip and knee prosthesis and osteosynthesis implants) compared with a conventional seven-day incubation period.

Cite this article: Bone Joint J 2013;95-B:1001–6.

Objectives

Ligaments which heal spontaneously have a healing process that is similar to skin wound healing. Menopause impairs skin wound healing and may likewise impair ligament healing. Our purpose in this study was to investigate the effect of surgical menopause on ligament healing in a rabbit medial collateral ligament model.

Objectives

This study aims to assess the correlation of CT-based structural rigidity analysis with mechanically determined axial rigidity in normal and metabolically diseased rat bone.

Gene therapy with insulin-like growth factor-1 (IGF-1) increases matrix production and enhances chondrocyte proliferation and survival in vitro. The purpose of this study was to determine whether arthroscopically-grafted chondrocytes genetically modified by an adenovirus vector encoding equine IGF-1 (AdIGF-1) would have a beneficial effect on cartilage healing in an equine femoropatellar joint model.

A total of 16 horses underwent arthroscopic repair of a single 15 mm cartilage defect in each femoropatellar joint. One joint received 2 × 10⁷ AdIGF-1 modified chondrocytes and the contralateral joint received 2 × 10⁷ naive (unmodified) chondrocytes. Repairs were analysed at four weeks, nine weeks and eight months after surgery. Morphological and histological appearance, IGF-1 and collagen type II gene expression (polymerase chain reaction, in situ hybridisation and immunohistochemistry), collagen type II content (cyanogen bromide and sodium dodecyl sulphate-polyacrylamide gel electrophoresis), proteoglycan content (dimethylmethylene blue assay), and gene expression for collagen type I, matrix metalloproteinase (MMP)-1, MMP-3, MMP-13, aggrecanase-1, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and TIMP-3 were evaluated.

Genetic modification of chondrocytes significantly increased IGF-1 mRNA and ligand production in repair tissue for up to nine weeks following transplantation. The gross and histological appearance of IGF-1 modified repair tissue was improved over control defects. Gross filling of defects was significantly improved at four weeks, and a more hyaline-like tissue covered the lesions at eight months. Histological outcome at four and nine weeks post-transplantation revealed greater tissue filling of defects transplanted with genetically modified chondrocytes, whereas repair tissue in control defects was thin and irregular and more fibrous. Collagen type II expression in IGF-1 gene-transduced defects was increased 100-fold at four weeks and correlated with increased collagen type II immunoreaction up to eight months.

Genetic modification of chondrocytes with AdIGF-1 prior to transplantation improved early (four to nine weeks), and to a lesser degree long-term, cartilage healing in the equine model.

The equine model of cartilage healing closely resembles human clinical cartilage repair. The results of this study suggest that cartilage healing can be enhanced through genetic modification of chondrocytes prior to transplantation.

Aspiration arthrography using an iodinated contrast medium is a useful tool for the investigation of septic or aseptic loosening of arthroplasties and of septic arthritis. Previously, the contrast media have been thought to cause false negative results in cultures when present in aspirated samples of synovial fluid, probably because free iodine is bactericidal, but reports have been inconclusive.

We examined the influence of the older, high osmolar contrast agents and the low osmolar media used currently on the growth of ten different micro-organisms capable of causing deep infection around a prosthesis. Five media were tested, using a disc diffusion technique and a time-killing curve method in which high and low inocula of micro-organisms were incubated in undiluted media. The only bactericidal effects were found with low inocula of Escherichia coli and Pseudomonas aeruginosa in ioxithalamate, one of the older ionic media.

The low and iso-osmolar iodinated contrast media used currently do not impede culture. Future study must assess other causes of false negative cultures of synovial fluid and new developments in enhancing microbial recovery from aspirated samples.

We carried out lacerations of 50%, followed by trimming, in ten turkey flexor tendons in vitro and measured the coefficient of friction at the tendon-pulley interface with loads of 200 g and 400 g and in 10°, 30°, 50° and 70° of flexion. Laceration increased the coefficient of friction from 0.12 for the intact tendon to 0.3 at both the test loads. Trimming the laceration reduced the coefficient of friction to 0.2. An exponential increase in the gliding resistance was found at 50° and 70° of flexion (p = 0.02 and p = 0.003, respectively) following trimming compared to that of the intact tendon.

We concluded that trimming partially lacerated flexor tendons will reduce the gliding resistance at the tendon-pulley interface, but will lead to fragmentation and triggering of the tendon at higher degrees of flexion and loading. We recommend that higher degrees of flexion be avoided during early post-operative rehabilitation following trimming of a flexor tendon.

We used a biodegradable mesh to convert an acetabular defect into a contained defect in six patients at total hip replacement. Their mean age was 61 years (46 to 69). The mean follow-up was 32 months (19 to 50). Before clinical use, the strength retention and hydrolytic in vitro degradation properties of the implants were studied in the laboratory over a two-year period. A successful clinical outcome was determined by the radiological findings and the Harris hip score.

All the patients had a satisfactory outcome and no mechanical failures or other complications were observed. No protrusion of any of the impacted grafts was observed beyond the mesh. According to our preliminary laboratory and clinical results the biodegradable mesh is suitable for augmenting uncontained acetabular defects in which the primary stability of the implanted acetabular component is provided by the host bone. In the case of defects of the acetabular floor this new application provides a safe method of preventing graft material from protruding excessively into the pelvis and the mesh seems to tolerate bone-impaction grafting in selected patients with primary and revision total hip replacement.

We used demineralised bone matrix (DBM) to augment re-attachment of tendon to a metal prosthesis in an in vivo ovine model of reconstruction of the extensor mechanism at the knee. We hypothesised that augmentation of the tendon-implant interface with DBM would enhance the functional and histological outcomes as compared with previously reported control reconstructions without DBM. Function was assessed at six and 12 weeks postoperatively, and histological examination was undertaken at 12 weeks.

A significant increase of 23.5% was observed in functional weight-bearing at six weeks in the DBM-augmented group compared with non-augmented controls (p = 0.004). By 12 weeks augmentation with DBM resulted in regeneration of a more direct-type enthesis, with regions of fibrocartilage, mineralised fibrocartilage and bone. In the controls the interface was predominantly indirect, with the tendon attached to the bone graft-hydroxyapatite base plate by perforating collagen fibres.

We evaluated the histological changes before and after fixation in ten knees of ten patients with osteochondritis dissecans who had undergone fixation of the unstable lesions. There were seven males and three females with a mean age of 15 years (11 to 22). The procedure was performed either using bio-absorbable pins only or in combination with an autologous osteochondral plug. A needle biopsy was done at the time of fixation and at the time of a second-look arthroscopy at a mean of 7.8 months (6 to 9) after surgery.

The biopsy specimens at the second-look arthroscopy showed significant improvement in the histological grading score compared with the pre-fixation scores (p < 0.01). In the specimens at the second-look arthroscopy, the extracellular matrix was stained more densely than at the time of fixation, especially in the middle to deep layers of the articular cartilage.

Our findings show that articular cartilage regenerates after fixation of an unstable lesion in osteochondritis dissecans.

We compared time-dependent changes in the biomechanical properties of single-and double-row repair of a simulated acute tear of the rotator cuff in rabbits to determine the effect of the fixation techniques on the healing process.

A tear of the supraspinatus tendon was created in 80 rabbits which were separated into two equal groups. A single-row repair with two suture anchors was conducted in group 1 and a double-row repair with four suture anchors in group 2. A total of ten intact contralateral shoulder joints was used as a control group. Biomechanical testing was performed immediately post-operatively and at four and eight weeks, and histological analysis at four and eight weeks.

The mean load to failure in group 2 animals was greater than in group 1, but both groups remained lower than the control group at all intervals. Histological analysis showed similar healing properties at four and eight weeks in both groups, but a significantly larger number of healed tendon-bone interfaces were identified in group 2 than in group 1 at eight weeks (p < 0.012).

The ultimate load to failure increased with the number of suture anchors used immediately post-operatively, and at four and eight weeks. The increased load to failure at eight weeks seemed to be related to the increase in the surface area of healed tendon-to-bone in the double-row repair group.

Although much has been published on the causes of slipped upper femoral epiphysis and the results of treatment, little attention has been given to the mechanism of the slip. This study presents the results of the analysis of 13 adolescent femora, and the attempts to reproduce the radiological appearances of a typical slip. The mean age of the skeletons was 13 years (11 to 15). It was found that the internal bony architecture in the zone of the growth plate was such that a slip of the epiphysis on the metaphysis (in the normal meaning of the word slip) could not take place, largely relating to the presence of a tubercle of bone projecting down from the epiphysis. The only way that the appearance of a typical slipped upper femoral epiphysis could be reproduced was by rotating the epiphysis posteromedially on the metaphysis. The presence and size of this peg-like tubercle was shown radiologically by CT scanning in one pair of intact adolescent femurs.

We performed a biomechanical study to compare the augmentation of isolated fractured vertebral bodies using two different bone tamps. Compression fractures were created in 21 vertebral bodies harvested from red deer after determining their initial strength and stiffness, which was then assessed after standardised bipedicular vertebral augmentation using a balloon or an expandable polymer bone tamp.

The median strength and stiffness of the balloon bone tamp group was 6.71 kN (sd 2.71) and 1.885 kN/mm (sd 0.340), respectively, versus 7.36 kN (sd 3.43) and 1.882 kN/mm (sd 0.868) in the polymer bone tamp group. The strength and stiffness tended to be greater in the polymer bone tamp group than in the balloon bone tamp group, but this difference was not statistically significant (strength p > 0.8, and stiffness p = 0.4).

We have undertaken a prospective study in patients with a fracture of the femoral shaft requiring intramedullary nailing to test the hypothesis that the femoral canal could be a potential source of the second hit phenomenon. We determined the local femoral intramedullary and peripheral release of interleukin-6 (IL-6) after fracture and subsequent intramedullary reaming.

In all patients, the fracture caused a significant increase in the local femoral concentrations of IL-6 compared to a femoral control group. The concentration of IL-6 in the local femoral environment was significantly higher than in the patients own matched blood samples from their peripheral circulation. The magnitude of the local femoral release of IL-6 after femoral fracture was independent of the injury severity score and whether the fracture was closed or open.

In patients who underwent intramedullary reaming of the femoral canal a further significant local release of IL-6 was demonstrated, providing evidence that intramedullary reaming can cause a significant local inflammatory reaction.

The effect of zoledronic acid on bone ingrowth was examined in an animal model in which porous tantalum implants were placed bilaterally within the ulnae of seven dogs. Zoledronic acid in saline was administered via a single post-operative intravenous injection at a dose of 0.1 mg/kg. The ulnae were harvested six weeks after surgery. Undecalcified transverse histological sections of the implant-bone interfaces were imaged with backscattered scanning electron microscopy and the percentage of available pore space that was filled with new bone was calculated. The mean extent of bone ingrowth was 6.6% for the control implants and 12.2% for the zoledronic acid-treated implants, an absolute difference of 5.6% (95% confidence interval, 1.2 to 10.1) and a relative difference of 85% which was statistically significant. Individual islands of new bone formation within the implant pores were similar in number in both groups but were 69% larger in the zoledronic acid-treated group. The bisphosphonate zoledronic acid should be further investigated for use in accelerating or enhancing the biological fixation of implants to bone.

The use of impaction bone grafting during revision arthroplasty of the hip in the presence of cortical defects has a high risk of post-operative fracture. Our laboratory study addressed the effect of extramedullary augmentation and length of femoral stem on the initial stability of the prosthesis and the risk of fracture.

Cortical defects in plastic femora were repaired using either surgical mesh without extramedullary augmentation, mesh with a strut graft or mesh with a plate. After bone impaction, standard or long-stem Exeter prostheses were inserted, which were tested by cyclical loading while measuring defect strain and migration of the stem.

Compared with standard stems without extramedullary augmentation, defect strains were 31% lower with longer stems, 43% lower with a plate and 50% lower with a strut graft. Combining extramedullary augmentation with a long stem showed little additional benefit (p = 0.67). The type of repair did not affect the initial stability. Our results support the use of impaction bone grafting and extramedullary augmentation of diaphyseal defects after mesh containment.

We report the effects of local administration of osteogenic protein-1 on the biomechanical properties of the overstretched anterior cruciate ligament in an animal model. An injury in the anterior cruciate ligament was created in 45 rabbits. They were divided into three equal groups. In group 1, no treatment was applied, in group II, phosphate-buffered saline was applied around the injured ligament, and in group III, 12.5 μg of osteogenic protein-1 mixed with phosphate-buffered saline was applied around the injured ligament. A control group of 15 rabbits was assembled from randomly-selected injured knees from among the first three groups. Each rabbit was killed at 12 weeks.

The maximum load and stiffness of the anterior cruciate ligament was found to be significantly greater in group III than either group 1 (p = 0.002, p = 0.014) or group II (p = 0.032, p = 0.025). The tensile strength and the tangent modulus of fascicles from the ligament were also significantly greater in group III than either group I (p = 0.002, p = 0.0174) or II (p = 0.005, p = 0.022).

The application of osteogenic protein-1 enhanced the healing in the injured anterior cruciate ligament, but compared with the control group the treated ligament remained lengthened. The administration of osteogenic protein-1 may have a therapeutic role in treating the overstretched anterior cruciate ligament.

Strains applied to bone can stimulate its development and adaptation. High strains and rates of strain are thought to be osteogenic, but the specific dose response relationship is not known. In vivo human strain measurements have been performed in the tibia to try to identify optimal bone strengthening exercises for this bone, but no measurements have been performed in the distal radial metaphysis, the most frequent site of osteoporotic fractures. Using a strain gauged bone staple, in vivo dorsal metaphyseal radial strains and rates of strain were measured in ten female patients during activities of daily living, standard exercises and falls on extended hands. Push-ups and falling resulted in the largest compression strains (median 1345 to 3146 με, equivalent to a 0.1345% to 0.3146% length change) and falling exercises in the largest strain rates (18 582 to 45 954 με/s). On the basis of their high strain and/or strain rates these or variations of these exercises may be appropriate for distal radial metaphyseal bone strengthening.