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Bone & Joint Research
Vol. 12, Issue 11 | Pages 691 - 701
3 Nov 2023
Dai Z Chen Y He E Wang H Guo W Wu Z Huang K Zhao Q

Aims

Osteoporosis is characterized by decreased trabecular bone volume, and microarchitectural deterioration in the medullary cavity. Interleukin-19 (IL-19), a member of the IL-10 family, is an anti-inflammatory cytokine produced primarily by macrophages. The aim of our study was to investigate the effect of IL-19 on osteoporosis.

Methods

Blood and femoral bone marrow suspension IL-19 levels were first measured in the lipopolysaccharide (LPS)-induced bone loss model. Small interfering RNA (siRNA) was applied to knock down IL-19 for further validation. Thereafter, osteoclast production was stimulated with IL-19 in combination with mouse macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL). The effect of IL-19 was subsequently evaluated using tartrate-resistant acid phosphatase (TRAP) staining and quantitative real-time polymerase chain reaction (RT-qPCR). The effect of IL-19 on osteoprotegerin (OPG) was then assessed using in vitro recombinant IL-19 treatment of primary osteoblasts and MLO-Y4 osteoblast cell line. Finally, transient transfection experiments and chromatin immunoprecipitation (ChIP) experiments were used to examine the exact mechanism of action.


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_7 | Pages 76 - 76
4 Apr 2023
LU X BAI S LIN Y YAN L LI L WANG M JIANG Z WANG H YANG B YANG Z WANG Y FENG L JIANG X PONOMAREV E LEE W LIN S KO H LI G
Full Access

Based on Ilizarov's law of tension-stress principle, distraction histogenesis technique has been widely applied in orthopaedic surgery for decades. Derived from this technique, cranial bone transport technique was mainly used for treating cranial deformities and calvarial defects. Recent studies reported that there are dense short vascular connections between skull marrow and meninges for immune cells trafficking, highlighting complex and tight association between skull and brain. Alzheimer's disease (AD) is a progressive neurodegenerative disease and the most common cause of dementia without effective therapy. Meningeal lymphatics have been recognized as an important mediator in neurological diseases. The augmentation of meningeal lymphatic drainage might be a promising therapeutic target for AD. Our proof-of-concept study has indicated that cranial bone transport can promote ischemic stroke recovery via modulating meningeal lymphatic drainage function, providing a rationale for treating AD using cranial bone maneuver (CBM). This study aims to investigate the effects of CBM on AD and to further explore the potential mechanisms.

Transgenic 5xFAD mice model was used in this study. After osteotomy, a bone flap was used to perform CBM without damaging the dura. Open filed test, novel object recognition test and Barn's maze test were used to evaluate neurological functions of 5xFAD mice after CBM treatment. Congo red and immunofluorescence staining were used to evaluate amyloid depositions and Aβ plaques in different brain regions. Lymphangiogenesis and the level of VEGF-C were examined after CBM treatment. OVA-A647 was intra-cisterna-magna injected to evaluate meningeal lymphatic drainage function after CBM treatment.

CBM significantly improved memory functions and reduced amyloid depositions and Aβ plaques in the hippocampus of 5xFAD mice. A significant increase of meningeal lymphatic vessels in superior sagittal sinus and transverse sinus, and the upregulation of VEGF-C in meninges were observed in 5xFAD mice treated with CBM. Moreover, CBM remarkably enhanced meningeal lymphatic drainage function in 5xFAD mice (n=5-16 mice/group for all studies).

CBM may promote meningeal lymphangiogenesis and lymphatic drainage function through VEGF-C-VEGFR3 pathway, and further reduce amyloid depositions and Aβ plaques and alleviate memory deficits in AD.


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_7 | Pages 48 - 48
4 Apr 2023
Yang Y Li Y Pan Q Wang H Bai S Pan X Ling K Li G
Full Access

Treatment for delayed wound healing resulting from peripheral vascular diseases and diabetic foot ulcers remain a challenge. A novel surgical technique named Tibial Cortex Transverse Transport has been developed for treating peripheral ischaemia, with encouraging clinical effects. However, its underlying mechanisms remain unclear. In present study, we aimed to explore the wound healing effects after undergoing this novel technique via multiple ways.

A novel rat model of Tibial Cortex Transverse Transport was established with a designed external fixator and effects on wound healing were investigated. All rats were randomized into 3 groups, with 12 rats per group: sham group (negative control), fixator group (positive control) and Tibial Cortex Transverse Transport group. Laser speckle perfusion imaging, vessel perfusion, histology and immunohistochemistry were used to evaluate the wound healing processes.

Gross and histological examinations showed that Tibial Cortex Transverse Transport technique accelerated wound closure and enhanced the quality of the newly formed skin tissues. In Tibial Cortex Transverse Transport group, HE staining demonstrated a better epidermis and dermis recovery, while immune-histochemical staining showed that Tibial Cortex Transverse Transport technique promoted local collagen deposition. Tibial Cortex Transverse Transport technique also benefited to angiogenesis and immunomodulation. In Tibial Cortex Transverse Transport group, blood flow in the wound area was higher than that ofother groups according to laser speckle imaging with more blood vessels observed. Enhanced neovascularization was seen in the Tibial Cortex Transverse Transport group with double immune-labelling of CD31 and α-SMA. The M2 macrophages at the wound site in the Tibial Cortex Transverse Transport group was also increased.

Tibial cortex transverse transport technique accelerated wound healing through enhanced angiogenesis and immunomodulation.


Bone & Joint Research
Vol. 11, Issue 7 | Pages 453 - 464
20 Jul 2022
Wang H Shi Y He F Ye T Yu S Miao H Liu Q Zhang M

Aims

Abnormal lipid metabolism is involved in the development of osteoarthritis (OA). Growth differentiation factor 11 (GDF11) is crucial in inhibiting the differentiation of bone marrow mesenchymal stem cells into adipocytes. However, whether GDF11 participates in the abnormal adipogenesis of chondrocytes in OA cartilage is still unclear.

Methods

Six-week-old female mice were subjected to unilateral anterior crossbite (UAC) to induce OA in the temporomandibular joint (TMJ). Histochemical staining, immunohistochemical staining (IHC), and quantitative real-time polymerase chain reaction (qRT-PCR) were performed. Primary condylar chondrocytes of rats were stimulated with fluid flow shear stress (FFSS) and collected for oil red staining, immunofluorescence staining, qRT-PCR, and immunoprecipitation analysis.


Aims

Treatment outcomes for methicillin-resistant Staphylococcus aureus (MRSA) periprosthetic joint infection (PJI) using systemic vancomycin and antibacterial cement spacers during two-stage revision arthroplasty remain unsatisfactory. This study explored the efficacy and safety of intra-articular vancomycin injections for PJI control after debridement and cement spacer implantation in a rat model.

Methods

Total knee arthroplasty (TKA), MRSA inoculation, debridement, and vancomycin-spacer implantation were performed successively in rats to mimic first-stage PJI during the two-stage revision arthroplasty procedure. Vancomycin was administered intraperitoneally or intra-articularly for two weeks to control the infection after debridement and spacer implantation.


Bone & Joint Research
Vol. 11, Issue 4 | Pages 189 - 199
13 Apr 2022
Yang Y Li Y Pan Q Bai S Wang H Pan X Ling K Li G

Aims

Treatment for delayed wound healing resulting from peripheral vascular diseases and diabetic foot ulcers remains a challenge. A novel surgical technique named ‘tibial cortex transverse transport’ (TTT) has been developed for treating peripheral ischaemia, with encouraging clinical effects. However, its underlying mechanisms remain unclear. In the present study, we explored the potential biological mechanisms of TTT surgery using various techniques in a rat TTT animal model.

Methods

A novel rat model of TTT was established with a designed external fixator, and effects on wound healing were investigated. Laser speckle perfusion imaging, vessel perfusion, histology, and immunohistochemistry were used to evaluate the wound healing processes.


Bone & Joint Research
Vol. 10, Issue 7 | Pages 411 - 424
14 Jul 2021
Zhao D Ren B Wang H Zhang X Yu M Cheng L Sang Y Cao S Thieringer FM Zhang D Wan Y Liu C

Aims

The use of 3D-printed titanium implant (DT) can effectively guide bone regeneration. DT triggers a continuous host immune reaction, including macrophage type 1 polarization, that resists osseointegration. Interleukin 4 (IL4) is a specific cytokine modulating osteogenic capability that switches macrophage polarization type 1 to type 2, and this switch favours bone regeneration.

Methods

IL4 at concentrations of 0, 30, and 100 ng/ml was used at day 3 to create a biomimetic environment for bone marrow mesenchymal stromal cell (BMMSC) osteogenesis and macrophage polarization on the DT. The osteogenic and immune responses of BMMSCs and macrophages were evaluated respectively.


Bone & Joint Research
Vol. 10, Issue 7 | Pages 401 - 410
13 Jul 2021
Liu Z Wang H Wang S Gao J Niu L

Aims

Poly (ADP-ribose) polymerase (PARP) inhibitor has been reported to attenuate inflammatory response in rat models of inflammation. This study was designed to investigate the effect of PARP signalling in osteoarthritis (OA) cartilage inflammatory response in an OA rat model.

Methods

The OA model was established by anterior cruciate ligament transection with medial meniscectomy in Wistar rats. The poly (ADP-ribose) polymerase 1 (PARP-1) shRNA (short hairpin (sh)-PARP-1) and negative control shRNA (sh-NC) were delivered using a lentiviral vector and were intra-articularly injected into rats after surgery. The weight-bearing distribution of the hind limbs and the knee joint width were measured every two weeks. The expression levels of PARP-1, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) in cartilage were determined using real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blot. The serum concentrations of inflammatory cytokines were detected using enzyme-linked immunosorbent assay (ELISA).


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_20 | Pages 20 - 20
1 Dec 2017
Xu L Chen X Wang H Wang F Wang Q
Full Access

Over the past decades, computer-aided navigation system has experienced tremendous development for minimising the risks and improving the precision of the surgery. Nowadays, some commercially-available and self-developed surgical navigation systems have already been tested and proved successfully for clinical applications. However, all of these systems use computer screen to render the navigation information such as the real-time position and orientation of the surgical instrument, virtual path of preoperative surgical planning, so that the surgeons have to switch between the actual operation site and computer screen which is inconvenient and impact the continuity of surgery. In recent years, Augmented Reality (AR)- based surgical navigation is a promising technology for clinical applications. In the AR system, virtual and actual reality are mixed, offering real-time, high-quality visualisation of an extensive variety of information to the users.

Therefore, in this study, a pilot study of a surgical navigation system for orthopaedics based on optical see-through augmented reality (AR-SNS) is presented, which encompasses the preoperative surgical planning, calibration, registration, and intra-operative tracking. With the aid of AR-SNS, the surgeon wearing the optical see-through head-mounted display can obtain a fused image that the 3D virtual critical anatomical structures are aligned with the actual structures of patient in intra-operative real-world scenario, so that some disadvantages of the traditional surgical navigation are overcome (For example, surgeon is no longer obliged to switch between the real operation scenario and computer screen), and the safety, accuracy, and reliability of the surgery may be improved.


Objectives

The lack of effective treatment for cartilage defects has prompted investigations using tissue engineering techniques for their regeneration and repair. The success of tissue-engineered repair of cartilage may depend on the rapid and efficient adhesion of transplanted cells to a scaffold. Our aim in this study was to repair full-thickness defects in articular cartilage in the weight-bearing area of a porcine model, and to investigate whether the CD44 monoclonal antibody biotin-avidin (CBA) binding technique could provide satisfactory tissue-engineered cartilage.

Methods

Cartilage defects were created in the load-bearing region of the lateral femoral condyle of mini-type pigs. The defects were repaired with traditional tissue-engineered cartilage, tissue-engineered cartilage constructed with the biotin-avidin (BA) technique, tissue-engineered cartilage constructed with the CBA technique and with autologous cartilage. The biomechanical properties, Western blot assay, histological findings and immunohistochemical staining were explored.


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_6 | Pages 77 - 77
1 Mar 2017
Wang H Foster J Franksen N Rolston L
Full Access

Background

More and more patients with end-stage knee OA are treated with total knee replacements (TKR). A modern TKR (Persona PS system, Zimmer Inc.) was designed with the hope to improve fit by providing additional sizing options on the femur and tibia. To date, there is very little information regarding the knee strength and knee mechanics during gait after the TKR. Furthermore, as a great percentage of knee OA patients have OA limited in one knee compartment and in the patellofemoral joint, a bi-compartmental knee replacement (BKR) (iDUO system, ConforMIS Inc.) was designed to treat OA at these affected areas. The BKR re-creates the individual's knee shape while correcting for any deformity. In addition, the BKR procedure results in less bone loss and retains the cruciate ligaments. To date, the influence of the BKR on knee strength and knee mechanics remains unknown. The purpose of the study was to evaluate knee strength and mechanics during level walking after the TKR and BKR surgeries.

Methods

Twelve healthy control participants (age=57±6 yr.; mass=82±11 kg; height=175±11 cm), eight patients (age=63±10 yr.; mass=87±20 kg; height=166±8 cm) with ten BKR systems (post-op time = 17±9 mo.), and nine patients (age=65±9 yr.; mass=90±35 kg; Height=169±12 cm) with twelve TKR systems (post-op time = 14±5 mo.) participated in the study. In a laboratory setting, maximal isometric knee strength was evaluated. Motion capture and 3D kinematic and kinetic analyses were conducted for level walking. One way ANOVA was used to determine differences among the BKR, TKR, and the healthy control knees.


Bone & Joint Research
Vol. 5, Issue 9 | Pages 412 - 418
1 Sep 2016
Ye S Ju B Wang H Lee K

Objectives

Interleukin 18 (IL-18) is a regulatory cytokine that degrades the disc matrix. Bone morphogenetic protein-2 (BMP-2) stimulates synthesis of the disc extracellular matrix. However, the combined effects of BMP-2 and IL-18 on human intervertebral disc degeneration have not previously been reported. The aim of this study was to investigate the effects of the anabolic cytokine BMP-2 and the catabolic cytokine IL-18 on human nucleus pulposus (NP) and annulus fibrosus (AF) cells and, therefore, to identify potential therapeutic and clinical benefits of recombinant human (rh)BMP-2 in intervertebral disc degeneration.

Methods

Levels of IL-18 were measured in the blood of patients with intervertebral disc degenerative disease and in control patients. Human NP and AF cells were cultured in a NP cell medium and treated with IL-18 or IL-18 plus BMP-2. mRNA levels of target genes were measured by real-time polymerase chain reaction, and protein levels of aggrecan, type II collagen, SOX6, and matrix metalloproteinase 13 (MMP13) were assessed by western blot analysis.


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_10 | Pages 27 - 27
1 May 2016
Sheng P Li Z Luo G Wang H Chen W Zhang Y Yang X
Full Access

Objective

To investigate the biomechanical mechanism and report preliminary clinical efficacy of eccentric rotational acetabular osteotomy (ERAO) when conduct treatment for developmental dysplasia of the hip (DDH).

Methods

Biomechanical model of the hip joint was established on six female cadaveric hips embalmed by formalin and stimulate ERAO was then performed on the model. Vertical force was loaded on the cadaveric spine from 0 N to 500 N and strain value on femoral head was measured preoperatively and postoperatively when loading force on spine reached the point of 100, 200, 300, 400 and 500 N. Stress value were then calculated base on the measurements. Besides, we reported postoperative follow up cases which were underwent ERAO to treat DDH in our hospital from July 2007 to October 2014. A total of 25 patients (26 hips) were reported, including 6 males and 19 females. Age varies from 11 to 57 years old, and the average age was 31 years old. Postoperative hip function was evaluated by Harris hip score and anteroposterior X⁃ray of pelvic was taken preoperatively and postoperatively to measure the Acetabular⁃head index (AHI), CE angle and Sharp angle.


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_4 | Pages 4 - 4
1 Jan 2016
Yang X Chen W Yu S Zhang Y Luo G Wang H Sheng P
Full Access

Objective

To investigate the biomechanical basis and report preliminary clinical efficacy of eccentric rotational acetabular osteotomy (ERAO) when treating developmental dysplasia of the hip (DDH).

Methods

Biomechanical model of the hip joint was established on cadaveric hips. After performed ERAO on the biomechanical model, we explored the impact of this surgery on biomechanics of the hip joint. Meanwhile, we reported postoperative follow-up cases who underwent ERAO in our hospital between November 2007 to July 2012. A total of 14 patients (15 hips) were reported, including 4 males and 10 females, mean age was 30 years old. Harris hip score was defined as clinical evaluation standard and radiographic assessment was based on the measurement and further comparison of pre- and post-operative AHI (Acetabular-head index), CE angle (Center-edge angle) and Sharp angle.


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_34 | Pages 310 - 310
1 Dec 2013
Frostick S Roebuck M Davidson J Santini A Peter V Banks J Williams A Wang H Thachil J Jackson R
Full Access

Introduction:

Wear debris from articulating joint implants is inevitable. Small debris particles are phagocytosed by macrophages. Larger particles initiate the fusion of many macrophages into multi-nucleated giant cells for particle encasement. Macrophages are recruited into inflamed tissues from the circulating monocyte population. Approximately 10% of white blood cells are monocytes which after release from the bone marrow circulate for 2–3 days, before being recruited into tissues as inflammatory macrophages or undergoing apoptosis. Circulating MRP8/14 (S100A8/A9) is a measure of monocyte recruitment, part of the monocyte-endothelial docking complex, and shed during monocyte transmigration across the endothelium. The higher the S100A8/A9 the more monocytes being recruited giving an indirect measure of debris production.

Methods:

2114 blood samples were collected from arthroplasty patients with hip or knee osteoarthritis (primary, post-traumatic and secondary), 589 before their primary arthroplasty, 1187 patients > 1 year post-arthroplasty, 101 patients before revision for aseptic loosening and 237 patients >1 year post-revision. Plasma S100A8/A9 was measured using BMA Biomedicals Elisa kit, normal levels in health adults are 0.5–3 mg/ml. Joint specific scores, WOMAC knee or Oxford Hip adjusted to percent of maximum, together with SF-12 were completed.


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_34 | Pages 311 - 311
1 Dec 2013
Frostick S Williams A Wang H Davidson J Santini A Thachil J Banks J Jackson R Roebuck M
Full Access

Introduction:

The risk factors for degenerative joint disease are well established: increasing age, obesity, joint abnormalities, trauma and overuse, together with female gender, ethnic and genetic factors. That obesity is a significant risk factor for developing osteoarthritis in non-weight-bearing as well as weight-bearing and joints was one of the first indications that the risk was nor purely that of aberrant biomechanical loading. Low grade chronic systemic inflammation is a component of each of ageing and obesity, atherosclerosis and diabetes, culminating in Metabolic Syndrome. In our study of 1684 patients with joint degeneration 85% were overweight or obese and 65% older than 65 years with 62% being both, 73% of patients were taking medications for serious, ‘non-orthopaedic’ health problems such as cardiovascular or respiratory disease, obesity or NIDDM. Monocytes are a major component of chronic inflammation, approximately 10% of white blood cells are monocytes which circulate for 2–3 days, before being recruited into tissues as inflammatory macrophages or undergoing apoptosis. Circulating S100A8/A9 (MRP8/14) is a measure of monocyte recruitment being shed during monocyte transmigration across the endothelium. The higher the S100A8/A9 the more monocytes being recruited giving an indirect measure of chronic inflammatory status.

Methods:

2154 blood samples were collected from arthroplasty patients (first or second joint replacement), 1135 Female and 1019 Male, age 29–93 years, body mass index (BMI) 18–56, with hip or knee osteoarthritis (primary, post-traumatic and secondary), 589 before a primary arthroplasty, 1187 patients >1 year post-arthroplasty, 101 patients before revision for aseptic loosening and 237 patients >1 year post-revision. All study patients received metal on UHMWPE implants. Plasma S100A8/A9 was measured using BMA Biomedicals Elisa kit, normal levels in healthy adults are 0.5–3 mg/ml. The data were analysed using SPSS, p values were calculated using Spearman's test.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVIII | Pages 5 - 5
1 Sep 2012
Carli A Gao C Khayyat-Kholghi M Wang H Li A Ladel C Harvey EJ Henderson J
Full Access

Purpose

Internal fixation of fractures in the presence of osteopenia has been associated with a failure rate as high as 25%. Enhancing bone formation and osseointegration of orthopaedic hardware is a priority when treating patients with impaired bone regenerative capacity. Fibroblast Growth Factor (FGF) 18 regulates skeletal development and could therefore have applications in implant integration. This study was designed to determine if FGF 18 promotes bone formation and osseointegration in the osteopenic FGFR3−/− mouse and to examine its effect on bone marrow derived mesenchymal stem cells (MSCs).

Method

In Vivo: Intramedullary implants were fabricated from 0.4 × 10mm nylon rods coated with 300nm of titanium by physical vapour deposition. Skeletally mature, age matched female FGFR3−/− and wild type mice received bilateral intramedullary femoral implants. Left femurs received an intramedullary injection of 0.1μg of FGF 18 (Merck Serono), and right femurs received saline only. Six weeks later, femurs were harvested, radiographed, scanned by micro CT, and processed for undecalcified for histology. In Vitro: MSCs were harvested from femurs and tibiae of skeletally mature age matched FGFR3−/− and wild type mice. Cells were cultured in Alpha Modified Eagles Medium (αMEM) to monitor proliferation or αMEM supplemented with ascorbic acid and sodium beta-glycerophosphate to monitor differentiation. Proliferation was assessed through cell counts and metabolic activity at days 3, 6 and 9. Differentiation was assessed through staining for osteoblasts and mineral deposition at days 6, 9 and 12.


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_II | Pages 178 - 178
1 May 2011
Wang H Weinsheimer N Schiltenwolf M
Full Access

Introduction: Long-term treatment of chronic muscu-loskeletal pain with opioids often causes a cluster of unpleasant side effects such as constipation, dizziness and cognitive impairment and is likely to lead to tolerance and to hyperalgesia, which is clinically important but not yet well researched. In this study we investigated the development of hyperalgesia after long-term treatment with opioids in patients with chronic low back pain (cLBP). The goal of this prospective longitudinal study was to investigate the long-term (> 1.5 years) effects of opioid analgetics on thermal sensation and pain thresholds and to follow the changes in pain sensitivity for 6 months during opioid withdrawal.

Methods: Using quantitative sensory testing (QST), we compared thermal sensation and pain thresholds on the palm of the hand and the low back bilaterally among three groups: patients with cLBP and long-term treatment with opioids (group 1, n=35); opioid-naive patients with chronic low back pain (group 2, n=34) and subjects with neither pain nor opioid intake (group 3, n=27). The effects of age, sex, pain duration, duration and dose of opioid intake, comorbidity (depression) and self-reported pain intensity assessed by QST were investigated.

All patients were allocated to a 3-week multidisciplinary functional restoration programme that emphasized biopsychosocial factors and included continuous tapering of opioid dose. During the study all patients kept records of the medication they used.

Results: Group 1 patients showed significantly delayed reaction to cold and warm stimuli on the back, compared with both group 2 and group 3. Pain thresholds for cold and heat on the hand were similar in group 1 and 2 but significantly reduced in these groups compared with group 3. Age, sex, pain duration, duration and dose of opioid intake, and self-reported pain intensity, but not depression, correlated significantly with QST results.

Discussion: The present study demonstrated that long-term opioid use significantly delayed thermal QST responses but had no measureable analgesic effects in patients with chronic low back pain. While the pain thresholds in groups 1 and 2 did not differ before opioid withdrawal, both groups 1 and 2 were more sensitive to pain than group 3 (healthy controls). This finding confirms that chronic low back pain itself might cause increased pain sensitivity, which seems not to be counteracted by opioid medication. Rather, treatment in the multidisciplinary pain therapy programme had positive effects on pain thresholds in opioid-naive patients but not in patients after opioid withdrawal. The opioid-naive patients of group 2 showed normalized pain thresholds 6 months after therapy, while the former opioid-positive patients of group 1 still had significantly decreased pain thresholds despite 6 months’ abstinence.


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_II | Pages 367 - 367
1 Jul 2008
Li G Wan C Wang H Carney D Ryaby J
Full Access

The thrombin-related peptide, TP508, a synthetic 23 amino acid peptide, has been shown to promote soft tissue, cartilage and fracture repair. We have previously demonstrated that two injections of TP508 have signifi-cantly enhanced bone consolidation in a rabbit model of distraction osteogenesis. This study was to test if a single injection of TP508 in a slow-releasing preparation will have the similar effects.

Unilateral tibial osteoectomies were stabilized with M100 Orthofix lengtheners in 17 male adult NZW rabbits. After 7 days, lengthening was initiated at a rate of 1.4 mm/day for 6 days. The following treatments were given: Group 1: TP508 in saline (300ug/300ul, n=6) was injected into the osteotomy gap at day of surgery and into the lengthening gap at end of lengthening. Group 2 (Control): Dextran gel (300ul, n=6) and Group 3: 300ul Dextran gel mixed with microspheres containing 300ug TP508 (n=5), was injected into the lengthening gap at end of lengthening. All animals were terminated 2 weeks after lengthening. Bone formation was assessed by weekly radiography and the specimens were subject to pQCT, microCT and histology examinations.

On radiographies there was more bone formation in the TP508 treated groups than that of the control group at 1st week post-lengthening and complete union was seen in 50% rabbits in Group 1, 33% in Group 2, and 60% in Group 3 at termination. The mean BMD of the regenerates was significantly higher in the TP508 treated groups than that of the control group (p< 0.05). MicroCT analysis demonstrated advanced bone formation in the TP508 treated animals. For histology, the regenerates were mainly consisted of woven bone of neocortilization and callus remodelling in Groups 1 and 3, whereas in Group 2, focal defects with cartilaginous tissues were frequently seen.

In conclusion we have demonstrated that a single injection of TP508 in the form of slow releasing micro-spheres has enhanced bone consolidation during distraction osteogenesis. TP508 may therefore be applied in the slow-releasing preparation for augmenting bone formation at reduced doses, costs and risks of infections through repeated injections.


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_I | Pages 129 - 129
1 Mar 2008
Mwale F Marguier G Wang H Petit A Huk O Zukor D Antoniou J
Full Access

Purpose: To develop an improved understanding of the in vivo behavior of intervertebral disc (IVD) cells for determining the phenotype of a differentiated stem cell in tissue engineering applications.

Methods: Nucleus pulposus (NP) and annulus fibrosus (AF) cells were isolated from adult bovine tails while notochordal cells were extracted from fetal bovine intervertebral disc. Ten million cells (of each cell type) in 500 & #61549;l of DMEM were then injected subcutaneously in C57Bl/6 mice. After 2 weeks, the mice were sacrificed and the specimens harvested. They were examined grossly, histologically and by scanning electronic microscopy (SEM) for the evidence of IVD-like structure formation. Proteoglycan was assessed by the GAG assay and PCR for analysis of gene expression. Control tissue (from bovine NP and AF) were directly fixed in glutaraldehyde, without any isolation technique and examined in SEM.

Results: After 2 weeks, SEM examination of specimens from AF and NP closely resembled normal bovine AF and NP. Of special interest here was the finding that some mice injected with cells from the AF developed an organized arrangement of parallel collagen fibres while NP cells injected mice had an amorphous structure with few collagen fibers. The GAG assay showed pro-teoglycan content for each samples, ranging from 3.8 microg to 26 microg. The morphology of the specimens retrieved from notochordal cells injected mice were also amorphous punctuated with thin collagen fibrils.

Conclusions: This study demonstrates that subcutaneous injection of bovine disc cells in mice can result in formation of disc structures similar to those of the bovine IVD. We believe that the cellular communication of the bovine disc cells is maintained in the mouse leading to architectural organization of the collagen fibers with the mouse as a source of nutrients. This technology may be useful in determining the phenotype of a differentiated stem cell for tissue engineering of IVD.