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Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_7 | Pages 5 - 5
1 May 2021
Jalal MMK Wallace RJ Peault B Simpson AHRW
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The role of mesenchymal stem cells (MSCs) in enhancing healing process has been examined with allogeneic and xenogeneic cells in transplantation models. However, certain factors might limit the use of allogeneic cells in clinical practice, (e.g. disease transmission, ethical issues and patient acceptance). Adipose tissue represents an abundant source for autologous cells. The aim of this study was to evaluate adipose-derived autologous cells for preventing non-union.

Adults male Wistar rats (n=5) underwent a previously published surgical procedure known to result in non-union if no treatment is given. This consisted of a mid-shaft tibial osteotomy with peri/endosteal stripping stabilised by intramedullary nail fixation with a 1mm gap maintained by a spacer. During the same operation, ipsilateral inguinal subcutaneous fat was harvested and processed for cell isolation. After three weeks in culture, the cell number reached 5×106 and were injected into the fracture site.

At the end of the experiment, all tibias (injected with autologous fat-MSCs) developed union. These were compared with a control group injected with PBS (n=4) and with allogenic (n=5) and xenogeneic (n=6) cell transplantation groups. The amount of callus was noticeably large in the autologous cell group and the distal-callus index was significantly greater than that of the other groups, P-value =<0.05, unpaired t-test, corrected by Benjamini & Hochberg.

We report a novel method for autologous MSCs implantation to stimulate fracture healing. Local injection of autologous fat-MSCs into the fracture site resulted in a solid union in all the tibias with statistically significantly greater amounts of callus.


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 4 | Pages 517 - 524
1 Apr 2011
Cox G McGonagle D Boxall SA Buckley CT Jones E Giannoudis PV

The scarcity of mesenchymal stem cells (MSCs) in iliac crest bone marrow aspirate (ICBMA), and the expense and time in culturing cells, has led to the search for alternative harvest sites. The reamer-irrigation-aspirator (RIA) provides continuous irrigation and suction during reaming of long bones. The aspirated contents pass via a filter, trapping bony fragments, before moving into a ‘waste’ bag from which MSCs have been previously isolated. We examined the liquid and solid phases, performed a novel digestion of the solid phase, and made a comparative assessment in terms of number, phenotype and differentiation capacity with matched ICBMA. The solid fraction from the filtrate was digested for 60 minutes at 37°C with collagenase. Enumeration was performed via the colony-forming unit fibroblast (CFU-F) assay. Passage (P2) cells were differentiated towards osteogenic, adipogenic and chondrogenic lineages, and their phenotypes assessed using flow cytometry (CD33, CD34, CD45, CD73, CD90, and CD105). MSCs from the RIA phases were able to differentiate at least as well as those from ICBMA, and all fractions had phenotypes consistent with other established sources. The median number of colonies for the three groups was: ICBMA = 8.5 (2 to 86), RIA-liquid = 19.5 (4 to 90), RIA-solid = 109 (67 to 200) per 200 μl. The mean total yield of cells for the three groups was: ICBMA = 920 (0 to 4275), RIA-liquid = 114 983 (16 500 to 477 750), RIA-solid = 12 785 (7210 to 28 475). The RIA filtrate contains large numbers of MSCs that could potentially be extracted without enzymatic digestion and used for bone repair without prior cell expansion


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVII | Pages 111 - 111
1 Sep 2012
Dallari D Del Piccolo N Savarino L Fantasia R Rani N Stagni C
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Introduction. We evaluated the osteogenic potential of a novel biomimetic bone paste (DBSint®), made of a combination of a human demineralized bone matrix (hDBM) and a nano-structured magnesium-enriched hydroxyapatite (Mg-HA), in a standardized clinical model of high tibial osteotomy for genu varus. Methods. A prospective, randomized, controlled study was performed and thirty patients were enrolled and assigned to three groups: DBSint® (Group I), nano-structured Mg-HA (SINTlife®) (Group II) and lyophilized-bone-chips (Group III). Six weeks after surgery, computed tomography-guided biopsies of the grafts were performed. Clinical/radiographic evaluation was performed at six weeks, twelve weeks, six months, one and 2 year after surgery, in order to verify if the graft type influenced the healing rate. Results. By histomorphometry, DBSint® was shown able to promote a quick and effective bone tissue regeneration, superior to the healing process occurred in presence of SINTlife® and lyophilized bone chips. At a mean follow up of 32,59 months, no statistical differences between the groups were found, both pre-and post-operatively, according to the Knee Society Scoring System. Mean time of ostointegration was 3,9 months in the DBSint® group, 4,2 months in the lyophilized-bone group and 4,5 in the SINTlife® group. Discussion/conclusion. Orthopedic practice may be adversely affected by an inadequate bone repair that might compromise the success of surgery. Therapy for bone regeneration with DBSint® could be particularly attractive in the treatment of patients with bone defects difficult to heal, where it could shorten the period necessary for bone regeneration, due to the higher osteogenetic potential


The Bone & Joint Journal
Vol. 99-B, Issue 4 | Pages 494 - 502
1 Apr 2017
Simpson AHRW Keenan G Nayagam S Atkins RM Marsh D Clement ND

Aims

The aim of this double-blind prospective randomised controlled trial was to assess whether low intensity pulsed ultrasound (LIPUS) accelerated or enhanced the rate of bone healing in adult patients undergoing distraction osteogenesis.

Patients and Methods

A total of 62 adult patients undergoing limb lengthening or bone transport by distraction osteogenesis were randomised to treatment with either an active (n = 32) or a placebo (n = 30) ultrasound device. A standardised corticotomy was performed in the proximal tibial metaphysis and a circular Ilizarov frame was used in all patients. The rate of distraction was also standardised. The primary outcome measure was the time to removal of the frame after adjusting for the length of distraction in days/cm for both the per protocol (PP) and the intention-to-treat (ITT) groups. The assessor was blinded to the form of treatment. A secondary outcome was to identify covariates affecting the time to removal of the frame.


Bone & Joint Research
Vol. 5, Issue 9 | Pages 427 - 435
1 Sep 2016
Stravinskas M Horstmann P Ferguson J Hettwer W Nilsson M Tarasevicius S Petersen MM McNally MA Lidgren L

Objectives

Deep bone and joint infections (DBJI) are directly intertwined with health, demographic change towards an elderly population, and wellbeing.

The elderly human population is more prone to acquire infections, and the consequences such as pain, reduced quality of life, morbidity, absence from work and premature retirement due to disability place significant burdens on already strained healthcare systems and societal budgets.

DBJIs are less responsive to systemic antibiotics because of poor vascular perfusion in necrotic bone, large bone defects and persistent biofilm-based infection. Emerging bacterial resistance poses a major threat and new innovative treatment modalities are urgently needed to curb its current trajectory.

Materials and Methods

We present a new biphasic ceramic bone substitute consisting of hydroxyapatite and calcium sulphate for local antibiotic delivery in combination with bone regeneration. Gentamicin release was measured in four setups: 1) in vitro elution in Ringer’s solution; 2) local elution in patients treated for trochanteric hip fractures or uncemented hip revisions; 3) local elution in patients treated with a bone tumour resection; and 4) local elution in patients treated surgically for chronic corticomedullary osteomyelitis.


The Bone & Joint Journal
Vol. 95-B, Issue 9 | Pages 1263 - 1268
1 Sep 2013
Savaridas T Wallace RJ Salter DM Simpson AHRW

Fracture repair occurs by two broad mechanisms: direct healing, and indirect healing with callus formation. The effects of bisphosphonates on fracture repair have been assessed only in models of indirect fracture healing.

A rodent model of rigid compression plate fixation of a standardised tibial osteotomy was used. Ten skeletally mature Sprague–Dawley rats received daily subcutaneous injections of 1 µg/kg ibandronate (IBAN) and ten control rats received saline (control). Three weeks later a tibial osteotomy was rigidly fixed with compression plating. Six weeks later the animals were killed. Fracture repair was assessed with mechanical testing, radiographs and histology.

The mean stress at failure in a four-point bending test was significantly lower in the IBAN group compared with controls (8.69 Nmm-2 (sd 7.63) vs 24.65 Nmm-2 (sd 6.15); p = 0.017). On contact radiographs of the extricated tibiae the mean bone density assessment at the osteotomy site was lower in the IBAN group than in controls (3.7 mmAl (sd 0.75) vs 4.6 mmAl (sd 0.57); p = 0.01). In addition, histological analysis revealed progression to fracture union in the controls but impaired fracture healing in the IBAN group, with predominantly cartilage-like and undifferentiated mesenchymal tissue (p = 0.007).

Bisphosphonate treatment in a therapeutic dose, as used for risk reduction in fragility fractures, had an inhibitory effect on direct fracture healing. We propose that bisphosphonate therapy not be commenced until after the fracture has united if the fracture has been rigidly fixed and is undergoing direct osteonal healing.

Cite this article: Bone Joint J 2013;95-B:1263–8.


The Bone & Joint Journal
Vol. 96-B, Issue 2 | Pages 259 - 262
1 Feb 2014
Guo KJ Zhao FC Guo Y Li FL Zhu L Zheng W

Corticosteroid use has been implicated in the development of osteonecrosis of the femoral head (ONFH). The exact mechanism and predisposing factors such as age, gender, dosage, type and combination of steroid treatment remain controversial. Between March and July 2003, a total of 539 patients with severe acute respiratory syndrome (SARS) were treated with five different types of steroid. There were 129 men (24%) and 410 women (76%) with a mean age of 33.7 years (21 to 59). Routine screening was undertaken with radiographs, MRI and/or CT to determine the incidence of ONFH.

Of the 129 male patients with SARS, 51 (39.5%) were diagnosed as suffering from ONFH, compared with only 79 of 410 female patients (19.3%). The incidence of ONFH in the patients aged between 20 and 49 years was much higher than that of the group aged between 50 and 59 years (25.9% (127 of 491) versus 6.3% (3 of 48); p = 0.018). The incidence of ONFH in patients receiving one type of steroid was 12.5% (21 of 168), which was much lower than patients receiving two different types (28.6%; 96 of 336) or three different types of steroid (37.1%; 13 of 35).

Cite this article: Bone Joint J 2014;96-B:259–62.


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 5 | Pages 698 - 703
1 May 2012
Soni A Tzafetta K Knight S Giannoudis PV

Controversy continues to surround the management of patients with an open fracture of the lower limb and an associated vascular injury (Gustilo type IIIC). This study reports our 15-year experience with these fractures and their outcome in 18 patients (15 male and three female). Their mean age was 30.7 years (8 to 54) and mean Mangled Extremity Severity Score (MESS) at presentation was 6.9 (3 to 10). A total of 15 lower limbs were salvaged and three underwent amputation (two immediate and one delayed). Four patients underwent stabilisation of the fracture by external fixation and 12 with an internal device. A total of 11 patients had damage to multiple arteries and eight had a vein graft. Wound cover was achieved with a pedicled flap in three and a free flap in six. Seven patients developed a wound infection and four developed nonunion requiring further surgery. At a mean follow-up of five years (4.1 to 6.6) the mean visual analogue scale for pain was 64 (10 to 90). Depression and anxiety were common. Activities were limited mainly because of pain, and the MESS was a valid predictor of the functional outcome. Distal tibial fractures had an increased rate of nonunion when associated with posterior tibial artery damage, and seven patients (39%) were not able to return to their previous occupation.