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Bone & Joint Research
Vol. 12, Issue 10 | Pages 615 - 623
3 Oct 2023
Helwa-Shalom O Saba F Spitzer E Hanhan S Goren K Markowitz SI Shilo D Khaimov N Gellman YN Deutsch D Blumenfeld A Nevo H Haze A

Aims

Cartilage injuries rarely heal spontaneously and often require surgical intervention, leading to the formation of biomechanically inferior fibrous tissue. This study aimed to evaluate the possible effect of amelogenin on the healing process of a large osteochondral injury (OCI) in a rat model.

Methods

A reproducible large OCI was created in the right leg femoral trochlea of 93 rats. The OCIs were treated with 0.1, 0.5, 1.0, 2.5, or 5.0 μg/μl recombinant human amelogenin protein (rHAM+) dissolved in propylene glycol alginate (PGA) carrier, or with PGA carrier alone. The degree of healing was evaluated 12 weeks after treatment by morphometric analysis and histological evaluation. Cell recruitment to the site of injury as well as the origin of the migrating cells were assessed four days after treatment with 0.5 μg/μl rHAM+ using immunohistochemistry and immunofluorescence.


Bone & Joint 360
Vol. 11, Issue 1 | Pages 24 - 27
1 Feb 2022


Introduction and Objective. Achilles tendon defect is difficult problem for orthopedic surgeon, and therefore the development of new treatments is desirable. Platelet-rich fibrin (PRF), dense fibrin scaffold composed of a fibrin matrix containing many growth factors, is recently used as regenerative medicine preparation. However, few data are available on the usefulness of PRF on Achilles tendon healing after injury. The objective of this study is to examine whether PRF promotes the healing of Achilles tendon defect in vivo and evaluated the effects of PRF on tenocytes in vitro. Materials and Methods. PRF were prepared from rats according to international guidelines on the literature. To create rat model for Achilles tendon defect, a 4-mm portion of the right Achilles tendon was completely resected, and PRF was placed into the gap in PRF group before sewing the gap with nylon sutures. To assess the histological healing of Achilles tendon defect, Bonar score was calculated using HE, Alcian-blue, and Picosirius-red staining section. Basso, Beattie, Bresnahan (BBB) score was used for the evaluation of motor functional recovery. Biomechanical properties including failure tensile load, ultimate tensile stress, breaking elongation, and elastic modulus were measured. We examined the effects of PRF on tenocytes isolated from rat Achilles tendon in vitro. The number of viable cells were measured by MTS assay, and immunostaining of ki-67 was used for detection of proliferative cells. Migration of tenocytes was evaluated by wound closure assay. Protein or gene expression level of extracellular matrix protein, such as collagen, were evaluated by immunoblotting, immunofluorescence, or PCR. Phosphorylation level of AKT, FGF receptor, or SMAD3 was determined by western blotting. Inhibitory experiments were performed using MK-2206 (AKT inhibitor), FIIN-2 (FGFR inhibitor), SB-431542 (TGF-B receptor inhibitor), or SIS3 (SMAD3 inhibitor). All p values presented are two-sided and p values < 0.05 were considered statistically significant. Results. In rat Achilles tendon defects, Bonar score was significantly improved in PRF group compared to control group. Collagen deposition at the site of Achilles tendon defect was observed earlier in PRF group. Consistent with the histological findings, BBB score was significantly improved in PRF group. PRF also significantly improved the biomechanical properties of injured Achilles tendon. Furthermore, proliferating tenocytes, labelled by ki-67 were significantly increased in PRF group. These data suggested PRF prompted the healing of Achilles tendon defect. Thus, we further examined the effects of PRF on tenocytes in vitro. PRF significantly increased the number of viable cells, the proliferative cells labelled by ki-67, and migratory ability. Furthermore, PRF significantly increased the protein expression levels of collagen-I, collagen-III, α-SMA, and tenascin-C in tenocytes. Next, we examined the signalling pathway associated with PRF-induced proliferation of tenocytes. PRF increased the phosphorylation level and induced nuclear translocation of AKT, known as key regulator of cell survival. PRF also induced the phosphorylation of FGF receptor. Inhibition of AKT or FGF-receptor completely suppressed the positive effects of PRF on tenocytes. Furthermore, we found that inhibition of FGF receptor partially suppressed the phosphorylation of AKT by PRF. Thus, PRF induced the proliferation of tenocytes via FGFR/AKT axis. We further evaluated the signalling pathway associated with PRF-induced expression of extracellular matrix. PRF increased the phosphorylation levels of SMAD3 and induced nuclear translocation of SMAD3. Furthermore, inhibition of TGF-B receptor or SMAD3 suppressed increased expression level of extracellular matrix by PRF. Thus, PRF increased expression level of extracellular matrix protein via TGF-BR/SMAD3 axis. Conclusions. PRF promotes tendon healing of the Achilles tendon defect and recovery of exercise performance and biomechanical properties. PRF increases the proliferation ability or protein expression level of extracellular matrix protein in tenocytes via FGFR/AKT or TGF-βR/SMAD3 axis, 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).


The Bone & Joint Journal
Vol. 103-B, Issue 7 Supple B | Pages 9 - 16
1 Jul 2021
Hadden WJ Ibrahim M Taha M Ure K Liu Y Paish ADM Holdsworth DW Abdelbary H

Aims

The aims of this study were to develop an in vivo model of periprosthetic joint infection (PJI) in cemented hip hemiarthroplasty, and to monitor infection and biofilm formation in real-time.

Methods

Sprague-Dawley rats underwent cemented hip hemiarthroplasty via the posterior approach with pre- and postoperative gait assessments. Infection with Staphylococcus aureus Xen36 was monitored with in vivo photoluminescent imaging in real-time. Pre- and postoperative gait analyses were performed and compared. Postmortem micro (m) CT was used to assess implant integration; field emission scanning electron microscopy (FE-SEM) was used to assess biofilm formation on prosthetic surfaces.


The Bone & Joint Journal
Vol. 103-B, Issue 3 | Pages 430 - 439
1 Mar 2021
Geary M Gaston RG Loeffler B

Upper limb amputations, ranging from transhumeral to partial hand, can be devastating for patients, their families, and society. Modern paradigm shifts have focused on reconstructive options after upper extremity limb loss, rather than considering the amputation an ablative procedure. Surgical advancements such as targeted muscle reinnervation and regenerative peripheral nerve interface, in combination with technological development of modern prosthetics, have expanded options for patients after amputation. In the near future, advances such as osseointegration, implantable myoelectric sensors, and implantable nerve cuffs may become more widely used and may expand the options for prosthetic integration, myoelectric signal detection, and restoration of sensation. This review summarizes the current advancements in surgical techniques and prosthetics for upper limb amputees.

Cite this article: Bone Joint J 2021;103-B(3):430–439.


Bone & Joint Research
Vol. 9, Issue 11 | Pages 742 - 750
1 Nov 2020
Li L Xiang S Wang B Lin H Cao G Alexander PG Tuan RS

Aims

Dystrophic calcification (DC) is the abnormal appearance of calcified deposits in degenerating tissue, often associated with injury. Extensive DC can lead to heterotopic ossification (HO), a pathological condition of ectopic bone formation. The highest rate of HO was found in combat-related blast injuries, a polytrauma condition with severe muscle injury. It has been noted that the incidence of HO significantly increased in the residual limbs of combat-injured patients if the final amputation was performed within the zone of injury compared to that which was proximal to the zone of injury. While aggressive limb salvage strategies may maximize the function of the residual limb, they may increase the possibility of retaining non-viable muscle tissue inside the body. In this study, we hypothesized that residual dead muscle tissue at the zone of injury could promote HO formation.

Methods

We tested the hypothesis by investigating the cellular and molecular consequences of implanting devitalized muscle tissue into mouse muscle pouch in the presence of muscle injury induced by cardiotoxin.


Bone & Joint Open
Vol. 1, Issue 8 | Pages 481 - 487
11 Aug 2020
Garner MR Warner SJ Heiner JA Kim YT Agel J

Aims

To compare results of institutional preferences with regard to treatment of soft tissues in the setting of open tibial shaft fractures.

Methods

We present a retrospective review of open tibial shaft fractures at two high-volume level 1 trauma centres with differing practices with regard to the acute management of soft tissues. Site 1 attempts acute primary closure, while site 2 prefers delayed closure/coverage. Comparisons include percentage of primary closure, number of surgical procedures until definitive closure, percentage requiring soft tissue coverage, and percentage of 90-day wound complication.


The Bone & Joint Journal
Vol. 102-B, Issue 7 | Pages 933 - 940
1 Jul 2020
Maempel JF Clement ND Wickramasinghe NR Duckworth AD Keating JF

Aims

The aim was to compare long-term patient-reported outcome measures (PROMs) after operative and nonoperative treatment of acute Achilles tendon rupture in the context of a randomized controlled trial.

Methods

PROMs including the Short Musculoskeletal Function Assessment (SMFA), Achilles Tendon Total Rupture Score (ATRS), EuroQol five-dimension (EQ-5D), satisfaction, net promoter score and data regarding re-rupture, and venous thromboembolic rates were collected for patients randomized to receive either operative or nonoperative treatment for acute Achilles tendon rupture in a previous study. Of the 80 patients originally randomized, 64 (33 treated surgically, 31 nonoperatively) patients were followed up at a mean of 15.7 years (13.4 to 17.7).


Bone & Joint Research
Vol. 9, Issue 5 | Pages 211 - 218
1 May 2020
Hashimoto A Miyamoto H Kobatake T Nakashima T Shobuike T Ueno M Murakami T Noda I Sonohata M Mawatari M

Aims

Biofilm formation is intrinsic to prosthetic joint infection (PJI). In the current study, we evaluated the effects of silver-containing hydroxyapatite (Ag-HA) coating and vancomycin (VCM) on methicillin-resistant Staphylococcus aureus (MRSA) biofilm formation.

Methods

Pure titanium discs (Ti discs), Ti discs coated with HA (HA discs), and 3% Ag-HA discs developed using a thermal spraying were inoculated with MRSA suspensions containing a mean in vitro 4.3 (SD 0.8) x 106 or 43.0 (SD 8.4) x 105 colony-forming units (CFUs). Immediately after MRSA inoculation, sterile phosphate-buffered saline or VCM (20 µg/ml) was added, and the discs were incubated for 24 hours at 37°C. Viable cell counting, 3D confocal laser scanning microscopy with Airyscan, and scanning electron microscopy were then performed. HA discs and Ag HA discs were implanted subcutaneously in vivo in the dorsum of rats, and MRSA suspensions containing a mean in vivo 7.2 (SD 0.4) x 106  or 72.0 (SD 4.2) x 105  CFUs were inoculated on the discs. VCM was injected subcutaneously daily every 12 hours followed by viable cell counting.


Bone & Joint Open
Vol. 2, Issue 1 | Pages 66 - 71
27 Jan 2020
Moriarty P Kayani B Wallace C Chang J Plastow R Haddad FS

Aims

Graft infection following anterior cruciate ligament reconstruction (ACLR) may lead to septic arthritis requiring multiple irrigation and debridement procedures, staged revision operations, and prolonged courses of antibiotics. To our knowledge, there are no previous studies reporting on how gentamicin pre-soaking of hamstring grafts influences infection rates following ACLR. We set out to examine this in our study accordingly.

Methods

This retrospective study included 2,000 patients (1,156 males and 844 females) who underwent primary ACLR with hamstring autografts between 2007 to 2017. This included 1,063 patients who received pre-soaked saline hamstring grafts for ACLR followed by 937 patients who received pre-soaked gentamicin hamstring grafts for ACLR. All operative procedures were completed by a single surgeon using a standardized surgical technique. Medical notes were reviewed and data relating to the following outcomes recorded: postoperative infection, clinical progress, causative organisms, management received, and outcomes.


The Bone & Joint Journal
Vol. 101-B, Issue 2 | Pages 124 - 131
1 Feb 2019
Isaacs J Cochran AR

Abstract

Nerve transfer has become a common and often effective reconstructive strategy for proximal and complex peripheral nerve injuries of the upper limb. This case-based discussion explores the principles and potential benefits of nerve transfer surgery and offers in-depth discussion of several established and valuable techniques including: motor transfer for elbow flexion after musculocutaneous nerve injury, deltoid reanimation for axillary nerve palsy, intrinsic re-innervation following proximal ulnar nerve repair, and critical sensory recovery despite non-reconstructable median nerve lesions.


The Bone & Joint Journal
Vol. 100-B, Issue 5 | Pages 590 - 595
1 May 2018
Sawa M Nakasa T Ikuta Y Yoshikawa M Tsuyuguchi Y Kanemitsu M Ota Y Adachi N

Aims. The aim of this study was to evaluate antegrade autologous bone grafting with the preservation of articular cartilage in the treatment of symptomatic osteochondral lesions of the talus with subchondral cysts. Patients and Methods. The study involved seven men and five women; their mean age was 35.9 years (14 to 70). All lesions included full-thickness articular cartilage extending through subchondral bone and were associated with subchondral cysts. Medial lesions were exposed through an oblique medial malleolar osteotomy, and one lateral lesion was exposed by expanding an anterolateral arthroscopic portal. After refreshing the subchondral cyst, it was grafted with autologous cancellous bone from the distal tibial metaphysis. The fragments of cartilage were fixed with 5-0 nylon sutures to the surrounding cartilage. Function was assessed at a mean follow-up of 25.3 months (15 to 50), using the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot outcome score. The radiological outcome was assessed using MRI and CT scans. Results. The mean AOFAS score improved from 65.7 (47 to 81) preoperatively to 92 (90 to 100) at final follow-up, with 100% patient satisfaction. The radiolucent area of the cysts almost disappeared on plain radiographs in all patients immediately after surgery, and there were no recurrences at the most recent follow-up. The medial malleolar screws were removed in seven patients, although none had symptoms. At this time, further arthroscopy was undertaken, when it was found that the mean International Cartilage Repair Society (ICRS) arthroscopic score represented near-normal cartilage. Conclusion. Autologous bone grafting with fixation of chondral fragments preserves the original cartilage in the short term, and could be considered in the treatment for adult patients with symptomatic osteochondral defect and subchondral cysts. Cite this article: Bone Joint J 2018;100-B:590–5


Bone & Joint Research
Vol. 7, Issue 3 | Pages 252 - 262
1 Mar 2018
Nishida K Matsushita T Takayama K Tanaka T Miyaji N Ibaraki K Araki D Kanzaki N Matsumoto T Kuroda R

Objectives

This study aimed to examine the effects of SRT1720, a potent SIRT1 activator, on osteoarthritis (OA) progression using an experimental OA model.

Methods

Osteoarthritis was surgically induced by destabilization of the medial meniscus in eight-week-old C57BL/6 male mice. SRT1720 was administered intraperitoneally twice a week after surgery. Osteoarthritis progression was evaluated histologically using the Osteoarthritis Research Society International (OARSI) score at four, eight, 12 and 16 weeks. The expression of SIRT1, matrix metalloproteinase 13 (MMP-13), a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5), cleaved caspase-3, PARP p85, and acetylated nuclear factor (NF)-κB p65 in cartilage was examined by immunohistochemistry. Synovitis was also evaluated histologically. Primary mouse epiphyseal chondrocytes were treated with SRT1720 in the presence or absence of interleukin 1 beta (IL-1β), and gene expression changes were examined by real-time polymerase chain reaction (PCR).


Bone & Joint 360
Vol. 6, Issue 4 | Pages 16 - 18
1 Aug 2017


Bone & Joint Research
Vol. 6, Issue 3 | Pages 154 - 161
1 Mar 2017
Liu J Li X Zhang H Gu R Wang Z Gao Z Xing L

Objectives

Ubiquitin E3 ligase-mediated protein degradation regulates osteoblast function. Itch, an E3 ligase, affects numerous cell functions by regulating ubiquitination and proteasomal degradation of related proteins. However, the Itch-related cellular and molecular mechanisms by which osteoblast differentiation and function are elevated during bone fracture repair are as yet unknown.

Methods

We examined the expression levels of E3 ligases and NF-κB members in callus samples during bone fracture repair by quantitative polymerase chain reaction (qPCR) and the total amount of ubiquitinated proteins by Western blot analysis in wild-type (WT) mice. The expression levels of osteoblast-associated genes in fracture callus from Itch knockout (KO) mice and their WT littermates were examined by qPCR. The effect of NF-κB on Itch expression in C2C12 osteoblast cells was determined by a chromatin immunoprecipitation (ChIP) assay.


Bone & Joint Research
Vol. 5, Issue 11 | Pages 577 - 585
1 Nov 2016
Hase E Sato K Yonekura D Minamikawa T Takahashi M Yasui T

Objectives

This study aimed to evaluate the histological and mechanical features of tendon healing in a rabbit model with second-harmonic-generation (SHG) imaging and tensile testing.

Materials and Methods

A total of eight male Japanese white rabbits were used for this study. The flexor digitorum tendons in their right leg were sharply transected, and then were repaired by intratendinous stitching. At four weeks post-operatively, the rabbits were killed and the flexor digitorum tendons in both right and left legs were excised and used as specimens for tendon healing (n = 8) and control (n = 8), respectively. Each specimen was examined by SHG imaging, followed by tensile testing, and the results of the two testing modalities were assessed for correlation.


The Bone & Joint Journal
Vol. 98-B, Issue 5 | Pages 647 - 653
1 May 2016
Owen DH Agius PA Nair A Perriman DM Smith PN Roberts CJ

Aims

Total wrist arthrodesis (TWA) produces a spectrum of outcomes. We investigated this by reviewing 77 consecutive TWA performed for inflammatory and post-traumatic arthropathies, wrist instability and as a salvage procedure.

Patients and Methods

All operations were performed by a single surgeon using a specifically designed pre-contoured dorsally applied non-locking wrist arthrodesis plate at a single centre.


Bone & Joint Research
Vol. 5, Issue 5 | Pages 185 - 190
1 May 2016
Yuenyongviwat V Iamthanaporn K Hongnaparak T Tangtrakulwanich B

Objectives. Nylon sutures and skin staples are used commonly in total knee arthroplasty (TKA) surgical wound closure. However, there is no study that compares the wound healing efficacy and patient satisfaction scores of both techniques in the same knee. Methods. We randomised 70 patients who underwent primary TKA into two groups. In one group of 34 patients, the skin at the upper half of the wound was closed with skin staples and the lower half of the wound was closed with simple interrupted nylon sutures. In the other group of 36 patients, the skin at the upper half of the wound was closed with nylon stitches and the lower half of the wound was closed with skin staples. We recorded the wound closure time, pain score at the time of stitch removal, wound complication rate, patient satisfaction score, and the Hollander wound evaluation score at the post-operative periods of five days, 14 days, six weeks, three months, and six months. Each half wound was analysed separately. Results. The mean patient body mass index was 26.8 kg/m. 2. (standard deviation 6.3). A total of 70 nylon stitched wounds and 70 skin stapled wounds were analysed. There were no significant differences in wound complication rates, patient satisfaction score, and the Hollander wound evaluation score between both types of wounds (p > 0.05). The wound closure time for skin stapled wounds was significantly lower than the nylon stitched wounds (p < 0.001). However, the skin stapled wounds had a significantly higher pain score at the time of stitch removal (p < 0.001). Conclusion. Skin staples and nylon stitches had comparable results with respect to wound healing and patient satisfaction in TKA wound closure in non-obese patients. The benefit of skin staples over nylon stitches was a decrease in operative time, but was more painful upon removal. Cite this article: V. Yuenyongviwat. A randomised controlled trial comparing skin closure in total knee arthroplasty in the same knee: nylon sutures versus skin staples. Bone Joint Res 2016;5:185–190. DOI: 10.1302/2046-3758.55.2000629


The Bone & Joint Journal
Vol. 98-B, Issue 4 | Pages 526 - 533
1 Apr 2016
Hanley EN Ode G Jackson III JB Seymour R

Aims

The purpose of this prospective study was to evaluate the outcomes of coccygectomy for patients with chronic coccydynia.

Patients and Methods

Between 2007 and 2011, 98 patients underwent coccygectomy for chronic coccydynia. The patients were aged > 18 years, had coccygeal pain, local tenderness and a radiological abnormality, and had failed conservative management. Outcome measures were the Short Form 36 (SF-36), the Oswestry Disability Index (ODI) and a visual analogue scale (VAS) for pain. Secondary analysis compared the pre-operative features and the outcomes of patients with successful and failed treatment, two years post-operatively. The threshold for success was based on a minimum clinically important difference (MCID) on the ODI of 20 points. All other patients, including those lost to follow-up, were classified as failures.