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The Journal of Bone & Joint Surgery British Volume
Vol. 81-B, Issue 5 | Pages 902 - 906
1 Sep 1999
Ochi M Iwasa J Uchio Y Adachi N Sumen Y

We examined whether somatosensory evoked potentials (SEPs) were detectable after direct electrical stimulation of injured, reconstructed and normal anterior cruciate ligaments (ACL) during arthroscopy under general anaesthesia. We investigated the position sense of the knee before and after reconstruction and the correlation between the SEP and instability. We found detectable SEPs in all ligaments which had been reconstructed with autogenous semitendinosus and gracilis tendons over the past 18 months as well as in all cases of the normal group. The SEP was detectable in only 15 out of 32 cases in the injured group, although the voltages in the injured group were significantly lower than those of the controls. This was not the case in the reconstructed group. The postoperative position sense in 17 knees improved significantly, but there was no correlation between it and the voltage. The voltage of stable knees was significantly higher than that of the unstable joints. Our findings showed that sensory reinnervation occurred in the reconstructed human ACL and was closely related to the function of the knee


Bone & Joint Research
Vol. 6, Issue 4 | Pages 208 - 215
1 Apr 2017
Decambron A Manassero M Bensidhoum M Lecuelle B Logeart-Avramoglou D Petite H Viateau V

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.


Bone & Joint Research
Vol. 6, Issue 2 | Pages 73 - 81
1 Feb 2017
Ishihara K Okazaki K Akiyama T Akasaki Y Nakashima Y

Objectives

Osteophytes are products of active endochondral and intramembranous ossification, and therefore could theoretically provide significant efficacy as bone grafts. In this study, we compared the bone mineralisation effectiveness of osteophytes and cancellous bone, including their effects on secretion of growth factors and anabolic effects on osteoblasts.

Methods

Osteophytes and cancellous bone obtained from human patients were transplanted onto the calvaria of severe combined immunodeficient mice, with Calcein administered intra-peritoneally for fluorescent labelling of bone mineralisation. Conditioned media were prepared using osteophytes and cancellous bone, and growth factor concentration and effects of each graft on proliferation, differentiation and migration of osteoblastic cells were assessed using enzyme-linked immunosorbent assays, MTS ((3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium)) assays, quantitative real-time polymerase chain reaction, and migration assays.


Bone & Joint Research
Vol. 5, Issue 9 | Pages 403 - 411
1 Sep 2016
Mrosek EH Chung H Fitzsimmons JS O’Driscoll SW Reinholz GG Schagemann JC

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.


Bone & Joint Research
Vol. 3, Issue 4 | Pages 130 - 138
1 Apr 2014
Shapiro F Connolly S Zurakowski D Flynn E Jaramillo D

Objectives

An experimental piglet model induces avascular necrosis (AVN) and deformation of the femoral head but its secondary effects on the developing acetabulum have not been studied. The aim of this study was to assess the development of secondary acetabular deformation following femoral head ischemia.

Methods

Intracapsular circumferential ligation at the base of the femoral neck and sectioning of the ligamentum teres were performed in three week old piglets. MRI was then used for qualitative and quantitative studies of the acetabula in operated and non-operated hips in eight piglets from 48 hours to eight weeks post-surgery. Specimen photographs and histological sections of the acetabula were done at the end of the study.


The Bone & Joint Journal
Vol. 95-B, Issue 11 | Pages 1581 - 1581
1 Nov 2013
Cook TM

We welcome letters to the Editor concerning articles that have recently been published. Such letters will be subject to the usual stages of selection and editing; where appropriate the authors of the original article will be offered the opportunity to reply.


Bone & Joint Research
Vol. 3, Issue 7 | Pages 230 - 235
1 Jul 2014
van der Jagt OP van der Linden JC Waarsing JH Verhaar JAN Weinans H

Objectives

Electromagnetic fields (EMF) are widely used in musculoskeletal disorders. There are indications that EMF might also be effective in the treatment of osteoporosis. To justify clinical follow-up experiments, we examined the effects of EMF on bone micro-architectural changes in osteoporotic and healthy rats. Moreover, we tested the effects of EMF on fracture healing.

Methods

EMF (20 Gauss) was examined in rats (aged 20 weeks), which underwent an ovariectomy (OVX; n = 8) or sham-ovariectomy (sham-OVX; n = 8). As a putative positive control, all rats received bilateral fibular osteotomies to examine the effects on fracture healing. Treatment was applied to one proximal lower leg (three hours a day, five days a week); the lower leg was not treated and served as a control. Bone architectural changes of the proximal tibia and bone formation around the osteotomy were evaluated using in vivo microCT scans at start of treatment and after three and six weeks.


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 1 | Pages 169 - 175
1 Jan 2010
Dutton AQ Choong PF Goh JC Lee EH Hui JHP

We hypothesised that meniscal tears treated with mesenchymal stem cells (MSCs) together with a conventional suturing technique would show improved healing compared with those treated by a conventional suturing technique alone. In a controlled laboratory study 28 adult pigs (56 knees) underwent meniscal procedures after the creation of a radial incision to represent a tear. Group 1 (n = 9) had a radial meniscal tear which was left untreated. In group 2 (n = 19) the incision was repaired with sutures and fibrin glue and in group 3, the experimental group (n = 28), treatment was by MSCs, suturing and fibrin glue.

At eight weeks, macroscopic examination of group 1 showed no healing in any specimens. In group 2 no healing was found in 12 specimens and incomplete healing in seven. The experimental group 3 had 21 specimens with complete healing, five with incomplete healing and two with no healing. Between the experimental group and each of the control groups this difference was significant (p < 0.001).

The histological and macroscopic findings showed that the repair of meniscal tears in the avascular zone was significantly improved with MSCs, but that the mechanical properties of the healed menisci remained reduced.


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 4 | Pages 586 - 594
1 Apr 2010
Sonnabend DH Howlett CR Young AA

The establishment of a suitable animal model of repair of the rotator cuff is difficult since the presence of a true rotator cuff anatomically appears to be restricted almost exclusively to advanced primates. Our observational study describes the healing process after repair of the cuff in a primate model. Lesions were prepared and repaired in eight ‘middle-aged’ baboons. Two each were killed at four, eight, 12 and 15 weeks post-operatively. The bone-tendon repair zones were assessed macroscopically and histologically.

Healing of the baboon supraspinatus involved a sequence of stages resulting in the reestablishment of the bone-tendon junction. It was not uniform and occurred more rapidly at the sites of suture fixation than between them. Four weeks after repair the bone-tendon healing was immature. Whereas macroscopically the repair appeared to be healed at eight weeks, the Sharpey fibres holding the repair together did not appear in any considerable number before 12 weeks. By 15 weeks, the bone-tendon junction was almost, but not quite mature.

Our results support the use of a post-operative rehabilitation programme in man which protects the surgical repair for at least 12 to 15 weeks in order to allow maturation of tendon-to-bone healing.


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 12 | Pages 1635 - 1640
1 Dec 2008
Spence G Phillips S Campion C Brooks R Rushton N

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.


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 6 | Pages 823 - 827
1 Jun 2006
White TO Clutton RE Salter D Swann D Christie J Robinson CM

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.


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 10 | Pages 1433 - 1438
1 Oct 2012
Lam W Guo X Leung K Kwong KSC

This study was designed to test the hypothesis that the sensory innervation of bone might play an important role in sensing and responding to low-intensity pulsed ultrasound and explain its effect in promoting fracture healing. In 112 rats a standardised mid-shaft tibial fracture was created, supported with an intramedullary needle and divided into four groups of 28. These either had a sciatic neurectomy or a patellar tendon resection as control, and received the ultrasound or not as a sham treatment. Fracture union, callus mineralisation and remodelling were assessed using plain radiography, peripheral quantitative computed tomography and histomorphology.

Daily ultrasound treatment significantly increased the rate of union and the volumetric bone mineral density in the fracture callus in the neurally intact rats (p = 0.025), but this stimulating effect was absent in the rats with sciatic neurectomy. Histomorphology demonstrated faster maturation of the callus in the group treated with ultrasound when compared with the control group. The results supported the hypothesis that intact innervation plays an important role in allowing low-intensity pulsed ultrasound to promote fracture healing.


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 1 | Pages 120 - 125
1 Jan 2011
Lim H Bae J Song H Teoh SH Kim H Kum D

Medial open-wedge high tibial osteotomy has been gaining popularity in recent years, but adequate supporting material is required in the osteotomy gap for early weight-bearing and rapid union. The purpose of this study was to investigate whether the implantation of a polycaprolactone-tricalcium phosphate composite scaffold wedge would enhance healing of the osteotomy in a micro pig model. We carried out open-wedge high tibial osteotomies in 12 micro pigs aged from 12 to 16 months. A scaffold wedge was inserted into six of the osteotomies while the other six were left open. Bone healing was evaluated after three and six months using plain radiographs, CT scans, measurement of the bone mineral density and histological examination.

Complete bone union was obtained at six months in both groups. There was no collapse at the osteotomy site, loss of correction or failure of fixation in either group. Staining with haematoxylin and eosin demonstrated that there was infiltration of new bone tissue into the macropores and along the periphery of the implanted scaffold in the scaffold group. The CT scans and measurement of the bone mineral density showed that at six months specimens in the scaffold group had a higher bone mineral density than in the control group, although the implantation of the polycaprolactone-tricalcium phosphate composite scaffold wedge did not enhance healing of the osteotomy.


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 11 | Pages 1614 - 1620
1 Nov 2010
Fini M Tschon M Ronchetti M Cavani F Bianchi G Mercuri M Alberghini M Cadossi R

Short intense electrical pulses transiently increase the permeability of the cell membrane, an effect known as electroporation. This can be combined with antiblastic drugs for ablation of tumours of the skin and subcutaneous tissue. The aim of this study was to test the efficacy of electroporation when applied to bone and to understand whether the presence of mineralised trabeculae would affect the capability of the electric field to porate the membrane of bone cells.

Different levels of electrical field were applied to the femoral bone of rabbits. The field distribution and modelling were simulated by computer. Specimens of bone from treated and control rabbits were obtained for histology, histomorphometry and biomechanical testing.

After seven days, the area of ablation had increased in line with the number of pulses and/or with the amplitude of the electrical field applied. The osteogenic activity in the ablated area had recovered by 30 days. Biomechanical testing showed structural integrity of the bone at both times.

Electroporation using the appropriate combination of voltage and pulses induced ablation of bone cells without affecting the recovery of osteogenic activity. It can be an effective treatment in bone and when used in combination with drugs, an option for the treatment of metastases.


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 4 | Pages 558 - 565
1 Apr 2011
Xie X Wang X Zhang G Liu Z Yao D Hung L Hung VW Qin L

Corticosteroids are prescribed for the treatment of many medical conditions and their adverse effects on bone, including steroid-associated osteoporosis and osteonecrosis, are well documented. Core decompression is performed to treat osteonecrosis, but the results are variable. As steroids may affect bone turnover, this study was designed to investigate bone healing within a bone tunnel after core decompression in an experimental model of steroid-associated osteonecrosis. A total of five 28-week-old New Zealand rabbits were used to establish a model of steroid-induced osteonecrosis and another five rabbits served as controls. Two weeks after the induction of osteonecrosis, core decompression was performed by creating a bone tunnel 3 mm in diameter in both distal femora of each rabbit in both the experimental osteonecrosis and control groups. An in vivo micro-CT scanner was used to monitor healing within the bone tunnel at four, eight and 12 weeks postoperatively. At week 12, the animals were killed for histological and biomechanical analysis.

In the osteonecrosis group all measurements of bone healing and maturation were lower compared with the control group. Impaired osteogenesis and remodelling within the bone tunnel was demonstrated in the steroid-induced osteonecrosis, accompanied by inferior mechanical properties of the bone.

We have confirmed impaired bone healing in a model of bone defects in rabbits with pulsed administration of corticosteroids. This finding may be important in the development of strategies for treatment to improve the prognosis of fracture healing or the repair of bone defects in patients receiving steroid treatment.


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 1 | Pages 159 - 163
1 Jan 2010
Aykut S Öztürk A Özkan Y Yanik K İlman AA Özdemir RM

We studied the effects of coating titanium implants with teicoplanin and clindamycin in 30 New Zealand White rabbits which were randomly assigned to three groups. The intramedullary canal of the left tibia of each rabbit was inoculated with 500 colony forming units of Staphylococcus aureus. Teicoplanin-coated implants were implanted into rabbits in group 1, clindamycin-coated implants into rabbits in group 2, and uncoated implants into those in group 3. All the rabbits were killed one week later. The implants were removed and cultured together with pieces of tibial bone and wound swabs. The rate of colonisation of the organisms in the three groups was compared.

Organisms were cultured from no rabbits in group 1, one in group 2 but from all in group 3. There was no significant difference between groups 1 and 2 (p = 1.000). There were significant differences between groups 1 and 3 and groups 2 and 3 (p < 0.001). Significant protection against bacterial colonisation and infection was found with teicoplanin- and clindamycin-coated implants in this experimental model.


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 11 | Pages 1606 - 1613
1 Nov 2010
Oshima S Ishikawa M Mochizuki Y Kobayashi T Yasunaga Y Ochi M

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.


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 1 | Pages 131 - 139
1 Jan 2011
Daugaard H Elmengaard B Andreassen TT Baas J Bechtold JE Soballe K

Impaction allograft is an established method of securing initial stability of an implant in arthroplasty. Subsequent bone integration can be prolonged, and the volume of allograft may not be maintained. Intermittent administration of parathyroid hormone has an anabolic effect on bone and may therefore improve integration of an implant.

Using a canine implant model we tested the hypothesis that administration of parathyroid hormone may improve osseointegration of implants surrounded by bone graft. In 20 dogs a cylindrical porous-coated titanium alloy implant was inserted into normal cancellous bone in the proximal humerus and surrounded by a circumferential gap of 2.5 mm. Morsellised allograft was impacted around the implant. Half of the animals were given daily injections of human parathyroid hormone (1–34) 5 μg/kg for four weeks and half received control injections. The two groups were compared by mechanical testing and histomorphometry. We observed a significant increase in new bone formation within the bone graft in the parathyroid hormone group. There were no significant differences in the volume of allograft, bone-implant contact or in the mechanical parameters.

These findings suggest that parathyroid hormone improves new bone formation in impacted morsellised allograft around an implant and retains the graft volume without significant resorption. Fixation of the implant was neither improved nor compromised at the final follow-up of four weeks.


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 1 | Pages 119 - 123
1 Jan 2009
Benson RT McDonnell SM Rees JL Athanasou NA Carr AJ

We assessed the predictive value of the macroscopic and detailed microscopic appearance of the coracoacromial ligament, subacromial bursa and rotator-cuff tendon in 20 patients undergoing subacromial decompression for impingement in the absence of full-thickness tears of the rotator cuff. Histologically, all specimens had features of degenerative change and oedema in the extracellular matrix. Inflammatory cells were seen, but there was no evidence of chronic inflammation. However, the outcome was not related to cell counts.

At three months the mean Oxford shoulder score had improved from 29.2 (20 to 40) to 39.4 (28 to 48) (p < 0.0001) and at six months to 45.5 (36 to 48) (p < 0.0001). At six months, although all patients had improved, the seven patients with a hooked acromion had done so to a less extent than those with a flat or curved acromion judged by their mean Oxford shoulder scores of 43.5 and 46.5 respectively (p = 0.046). All five patients with partial-thickness tears were within this group and demonstrated less improvement than the patients with no tear (mean Oxford shoulder scores 43.2 and 46.4, respectively, p = 0.04). These findings imply that in the presence of a partial-thickness tear subacromial decompression may require additional specific treatment to the rotator cuff if the outcome is to be improved further.


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 10 | Pages 1386 - 1391
1 Oct 2008
Ozbaydar M Elhassan B Esenyel C Atalar A Bozdag E Sunbuloglu E Kopuz N Demirhan M

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.


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 12 | Pages 1666 - 1669
1 Dec 2006
Shisha T Kiss S Pap K Simpson H Szöke G

The response of the muscle is critical in determining the functional outcome of limb lengthening. We hypothesised that muscle response would vary with age and therefore studied the response of the muscles during tibial lengthening in ten young and ten mature rabbits. A bromodeoxyuridine technique was used to identify the dividing cells.

The young rabbits demonstrated a significantly greater proliferative response to the distraction stimulus than the mature ones. This was particularly pronounced at the myotendinous junction, but was also evident within the muscle belly.

Younger muscle adapted better to lengthening, suggesting that in patients in whom a large degree of muscle lengthening is required it may be beneficial to carry out this procedure when they are young, in order to achieve the optimal functional result.


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 7 | Pages 966 - 972
1 Jul 2008
Kawasumi M Kitoh H Siwicka KA Ishiguro N

The aim of our study was to investigate the effect of platelet-rich plasma on the proliferation and differentiation of rat bone-marrow cells and to determine an optimal platelet concentration in plasma for osseous tissue engineering. Rat bone-marrow cells embedded in different concentrations of platelet-rich plasma gel were cultured for six days. Their potential for proliferation and osteogenic differentiation was analysed. Using a rat limb-lengthening model, the cultured rat bone-marrow cells with platelet-rich plasma of variable concentrations were transplanted into the distraction gap and the quality of the regenerate bone was evaluated radiologically.

Cellular proliferation was enhanced in all the platelet-rich plasma groups in a dose-dependent manner. Although no significant differences in the production and mRNA expression of alkaline phosphatase were detected among these groups, mature bone regenerates were more prevalent in the group with the highest concentration of platelets.

Our results indicate that a high platelet concentration in the platelet-rich plasma in combination with osteoblastic cells could accelerate the formation of new bone during limb-lengthening procedures.


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 5 | Pages 726 - 736
1 May 2010
Hee HT Ismail HD Lim CT Goh JCH Wong HK

Although success has been achieved with implantation of bone marrow mesenchymal stem cells (bMSCs) in degenerative discs, its full potential may not be achieved if the harsh environment of the degenerative disc remains. Axial distraction has been shown to increase hydration and nutrition. Combining both therapies may have a synergistic effect in reversing degenerative disc disease. In order to evaluate the effect of bMSC implantation, axial distraction and combination therapy in stimulating regeneration and retarding degeneration in degenerative discs, we first induced disc degeneration by axial loading in a rabbit model.

The rabbits in the intervention groups performed better with respect to disc height, morphological grading, histological scoring and average dead cell count. The groups with distraction performed better than those without on all criteria except the average dead cell count.

Our findings suggest that bMSC implantation and distraction stimulate regenerative changes in degenerative discs in a rabbit model.


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 8 | Pages 1110 - 1114
1 Aug 2007
Biant LC Bentley G

Implantation of autologous chondrocytes and matrix autologous chondrocytes are techniques of cartilage repair used in the young adult knee which require harvesting of healthy cartilage and which may cause iatrogenic damage to the joint. This study explores alternative sources of autologous cells.

Chondrocytes obtained from autologous bone-marrow-derived cells and those from the damaged cartilage within the lesion itself are shown to be viable alternatives to harvest-derived cells. A sufficient number and quality of cells were obtained by the new techniques and may be suitable for autologous chondrocyte and matrix autologous chondrocyte implantation.


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 4 | Pages 557 - 564
1 Apr 2009
Rumian AP Draper ERC Wallace AL Goodship AE

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.


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 9 | Pages 1253 - 1260
1 Sep 2007
Karachalios T Boursinos L Poultsides L Khaldi L Malizos KN

We have evaluated the effect of the short-term administration of low therapeutic doses of modern COX-2 inhibitors on the healing of fractures.

A total of 40 adult male New Zealand rabbits were divided into five groups. A mid-diaphyseal osteotomy of the right ulna was performed and either normal saline, prednisolone, indometacin, meloxicam or rofecoxib was administered for five days. Radiological, biomechanical and histomorphometric evaluation was performed at six weeks.

In the group in which the highly selective anti-COX-2 agent, rofecoxib, was used the incidence of radiologically-incomplete union was similar to that in the control group. All the biomechanical parameters were statistically significantly lower in both the prednisolone and indometacin (p = 0.01) and in the meloxicam (p = 0.04) groups compared with the control group. Only the fracture load values were found to be statistically significantly lower (p = 0.05) in the rofecoxib group. Histomorphometric parameters were adversely affected in all groups with the specimens of the rofecoxib group showing the least negative effect.

Our findings indicated that the short-term administration of low therapeutic doses of a highly selective COX-2 inhibitor had a minor negative effect on bone healing.


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 4 | Pages 583 - 587
1 Apr 2005
Szöke G Lee S Simpson AHRW Prescott J

Little is known about the increase in length of tendons in postnatal life or of their response to limb lengthening procedures. A study was carried out in ten young and nine adult rabbits in which the tibia was lengthened by 20% at two rates 0.8 mm/day and 1.6 mm/day.

The tendon of the flexor digitorum longus (FDL) muscle showed a significant increase in length in response to lengthening of the tibia. The young rabbits exhibited a significantly higher increase in length in the FDL tendon compared with the adults. There was no difference in the amount of lengthening of the FDL tendon at the different rates. Of the increase in length which occurred, 77% was in the proximal half of the tendon.

This investigation demonstrated that tendons have the ability to lengthen during limb distraction. This occurred to a greater extent in the young who showed a higher proliferative response, suggesting that there may be less need for formal tendon lengthening in young children.


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 1 | Pages 121 - 126
1 Jan 2007
Jensen TB Overgaard S Lind M Rahbek O Bünger C Søballe K

Impacted bone allograft is often used in revision joint replacement. Hydroxyapatite granules have been suggested as a substitute or to enhance morcellised bone allograft. We hypothesised that adding osteogenic protein-1 to a composite of bone allograft and non-resorbable hydroxyapatite granules (ProOsteon) would improve the incorporation of bone and implant fixation. We also compared the response to using ProOsteon alone against bone allograft used in isolation. We implanted two non-weight-bearing hydroxyapatite-coated implants into each proximal humerus of six dogs, with each implant surrounded by a concentric 3 mm gap. These gaps were randomly allocated to four different procedures in each dog: 1) bone allograft used on its own; 2) ProOsteon used on its own; 3) allograft and ProOsteon used together; or 4) allograft and ProOsteon with the addition of osteogenic protein-1.

After three weeks osteogenic protein-1 increased bone formation and the energy absorption of implants grafted with allograft and ProOsteon. A composite of allograft, ProOsteon and osteogenic protein-1 was comparable, but not superior to, allograft used on its own.

ProOsteon alone cannot be recommended as a substitute for allograft around non-cemented implants, but should be used to extend the volume of the graft, preferably with the addition of a growth factor.


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 11 | Pages 1533 - 1538
1 Nov 2006
Meyer DC Lajtai G von Rechenberg B Pfirrmann CWA Gerber C

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.


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 2 | Pages 258 - 264
1 Feb 2007
Nagura I Fujioka H Kokubu T Makino T Sumi Y Kurosaka M

We developed a new porous scaffold made from a synthetic polymer, poly(DL-lactide-co-glycolide) (PLG), and evaluated its use in the repair of cartilage. Osteochondral defects made on the femoral trochlear of rabbits were treated by transplantation of the PLG scaffold, examined histologically and compared with an untreated control group.

Fibrous tissue was initially organised in an arcade array with poor cellularity at the articular surface of the scaffold. The tissue regenerated to cartilage at the articular surface. In the subchondral area, new bone formed and the scaffold was absorbed. The histological scores were significantly higher in the defects treated by the scaffold than in the control group (p < 0.05).

Our findings suggest that in an animal model the new porous PLG scaffold is effective for repairing full-thickness osteochondral defects without cultured cells and growth factors.


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 10 | Pages 1392 - 1400
1 Oct 2008
Hayashi R Kondo E Tohyama H Saito T Yasuda K

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.


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 1 | Pages 123 - 128
1 Jan 2006
Fini M Giavaresi G Giardino R Cavani F Cadossi R

We investigated the effect of stimulation with a pulsed electromagnetic field on the osseointegration of hydroxyapatite in cortical bone in rabbits. Implants were inserted into femoral cortical bone and were stimulated for six hours per day for three weeks.

Electromagnetic stimulation improved osseointegration of hydroxyapatite compared with animals which did not receive this treatment in terms of direct contact with the bone, the maturity of the bone and mechanical fixation. The highest values of maximum push-out force (Fmax) and ultimate shear strength (σu) were observed in the treated group and differed significantly from those of the control group at three weeks (Fmax; p < 0.0001; σu, p < 0.0005).


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 8 | Pages 1099 - 1109
1 Aug 2007
Munirah S Samsudin OC Chen HC Salmah SHS Aminuddin BS Ruszymah BHI

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 Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 9 | Pages 1292 - 1297
1 Sep 2005
Lietman SA Inoue N Rafiee B Deitz LW Chao EYS

We used a canine intercalary bone defect model to determine the effects of recombinant human osteogenic protein 1 (rhOP-1) on allograft incorporation. The allograft was treated with an implant made up of rhOP-1 and type I collagen or with type I collagen alone.

Radiographic analysis showed an increased volume of periosteal callus in both test groups compared with the control group at weeks 4, 6, 8 and 10. Mechanical testing after 12 weeks revealed increased maximal torque and stiffness in the rhOP-1 treated groups compared with the control group.

These results indicate a benefit from the use of an rhOP-1 implant in the healing of bone allografts. The effect was independent of the position of the implant. There may be a beneficial clinical application for this treatment.


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 5 | Pages 721 - 729
1 May 2005
Yanai T Ishii T Chang F Ochiai N

We produced large full-thickness articular cartilage defects in 33 rabbits in order to evaluate the effect of joint distraction and autologous culture-expanded bone-marrow-derived mesenchymal cell transplantation (ACBMT) at 12 weeks. After fixing the knee on a hinged external fixator, we resected the entire surface of the tibial plateau. We studied three groups: 1) with and without joint distraction; 2) with joint distraction and collagen gel, and 3) with joint distraction and ACBMT and collagen gel.

The histological scores were significantly higher in the groups with ACBMT collagen gel (p < 0.05). The area of regenerated soft tissue was smaller in the group allowed to bear weight (p < 0.05). These findings suggest that the repair of large defects of cartilage can be enhanced by joint distraction, collagen gel and ACBMT.