Periosteum is important for bone homoeostasis through the release of bone morphogenetic proteins (BMPs) and their effect on osteoprogenitor cells. Smoking has an adverse effect on fracture healing and bone regeneration. The aim of this study was to evaluate the effect of smoking on the expression of the BMPs of human periosteum. Real-time polymerase chain reaction was performed for BMP-2,-4,-6,-7 gene expression in periosteal samples obtained from 45 fractured bones (19 smokers, 26 non-smokers) and 60 non-fractured bones (21 smokers, 39 non-smokers). A hierarchical model of BMP gene expression (BMP-2 > BMP-6 > BMP-4 > BMP-7) was demonstrated in all samples. When smokers and non-smokers were compared, a remarkable reduction in the gene expression of BMP-2, -4 and -6 was noticed in smokers. The comparison of fracture and non-fracture groups demonstrated a higher gene expression of BMP-2, -4 and -7 in the non-fracture samples. Within the subgroups (fracture and non-fracture), BMP gene expression in smokers was either lower but without statistical significance in the majority of BMPs, or similar to that in non-smokers with regard to BMP-4 in fracture and BMP-7 in non-fracture samples. In smokers, BMP gene expression of human periosteum was reduced, demonstrating the effect of smoking at the molecular level by reduction of mRNA transcription of periosteal BMPs. Among the BMPs studied, BMP-2 gene expression was significantly higher, highlighting its role in bone homoeostasis

The results for autologous chondrocyte implantation (ACI) in the treatment of osteochondral defects in the knee are encouraging. At present, two techniques have been described to retain the chondrocyte suspension within the defect. The first involves using a periosteal flap harvested from the distal femur and the second involves using a type I/III collagen membrane. To the authors' knowledge there are no comparative studies of these two techniques in the current literature. A total of 68 patients with a mean age of 30.52 years (range 15 to 52 years) with symptomatic articular cartilage defects were randomised to have either ACI with a periosteal cover (33 patients) or ACI with a type I/III collagen cover (35 patients). The mean defect size was 4.54 cm. 2. (range 1 to 12 cm. 2. ). All patients were followed up at 24 months. A functional assessment using the Modified Cincinnati score showed that 74% of patients had a good or excellent result following the ACI with collagen cover compared with 67% after the ACI with periosteum cover at 2 years (p>0.05). Arthroscopy at 1 year also demonstrated similar results for both techniques. However, 36.4% of the periosteum covered grafts required shaving for hypertrophy compared with 1 patient for the collagen covered technique. This prospective, randomised study has shown no statistical difference between the clinical outcome of ACI with a periosteal cover versus ACI with a collagen cover at 2 years. A significant number of patients who had the ACI with periosteum technique required shaving of a hypertrophied graft within the first year of surgery. We conclude that there is no advantage in using periosteum as a cover for retaining the chondrocytes within an osteochondral defect; as a result we advocate the use of an alternative cover such as a porcine-derived, type I/III collagen membrane

Introduction. The presence of pluripotent mesenchymal cells in the periosteum along with the growth factors produced or released following injury provides this tissue with an important role in bone healing. Utilising this property, vascularised periosteal flaps may increase the union rates in recalcitrant atrophic long bone non-union. The novel chimeric fibula-periosteal flap utilises the periosteum raised on an independent periosteal vessel, thus allowing the periosteum to be inset freely around the osteotomy site, improving bone biology. Materials & Methods. Ten patients, with established non-union, underwent fibula-periosteal chimeric flaps (2016–2022) at the Canniesburn Plastic Surgery Unit, UK. Preoperative CT angiography was performed to identify the periosteal branches. A case-control approach was used. Patients acted as their own controls, which obviated patient specific risks for non-union. One osteotomy site was covered by the chimeric periosteal flap and one without. In two patients both the osteotomies were covered using a long periosteal flap. Results. Union rate of 100% (11/11) was noted with periosteal flap osteotomies, versus those without flaps at 28.6% (2/7) (p = 0.0025). Time to union was also reduced in the periosteal flaps at 8.5 months versus 16.75 months in the control group (p = 0.023). Survival curves with a hazard ratio of 4.1, equating to a 4 times higher chance of union with periosteal flaps (log-rank p = 0.0016) was observed. Conclusions. The chimeric fibula-periosteal flap provides an option for atrophic recalcitrant non-unions where use of vascularised fibula graft alone may not provide an adequate biological environment for consolidation

Abstract. Objectives. To determine the effectiveness of LIA compared to ACB in providing pain relief and reducing opiates usage in hamstring graft ACL reconstructions. Materials and Methods. In a consecutive series of hamstring graft ACL reconstructions, patients received three different regional and/or anaesthetic techniques for pain relief. Three groups were studied: group 1: general anaesthetic (GA)+ ACB (n=38); group 2: GA + ACB + LIA (n=31) and group 3: GA+LIA (n=36). ACB was given under ultrasound guidance. LIA involved infiltration at skin incision site, capsule, periosteum and in the hamstring harvest tunnel. Analgesic medications were similar between the three groups as per standard multimodal analgesia (MMA). Patients were similar in demographics distribution and surgical technique. The postoperative pain and total morphine requirements were evaluated and recorded. The postoperative pain was assessed using the visual analogue scores (VAS) at 0hrs, 2hrs, 4hrs, weight bearing (WB) and discharge (DC). Results. There was no statistically significant difference in opiates intake amongst the three groups. When comparing VAS scores; there were no statistical difference between the groups at any of the time intervals that VAS was measured. However, the GA+LIA group hospital's LOS (m=2.31hrs, SD=0.75) was almost half that of GA+ACB group (m=4.24hrs, SD=1.08); (conditions t(72)=8.88; p=0.000). There was no statistical significance in the incidence of adverse effects amongst the groups. Conclusion. The LIA technique provided equally good pain relief following hamstring graft ACL reconstructions when compared to ACB, while allowing for earlier rehabilitation, mobilisation and discharge

Introduction. Circumferential periosteal release is a rarely reported procedure for paediatric limb lengthening. The technique involves circumferential excision of a strip of periosteum from the metaphysis of the distal femur, tibia and fibula. This study aims to determine the mid to long-term effectiveness of this technique. Materials and Methods. A retrospective case series was performed of all patients undergoing circumferential periosteal release of the distal femur and/or tibia between 2006 and 2017. Data collected included demographics, surgical indication, post-operative limb-lengths and complications. Data collection was stopped if a further procedure was performed that may affect limb-length (except a further release). Leg-length discrepancies were calculated as absolute values and as percentages of the longer limb-length. Final absolute and percentage discrepancies were compared to initial discrepancies using a paired t-test. Results. Eighteen patients (11 males) were identified, who underwent 25 procedures. The mean age at first surgery was 5.83 (SD 3.49). The commonest indication was congenital limb deficiency (13 patients). In 23 procedures the periosteum was released in two limb segments (distal femur and distal tibia), whereas in two patients it was released in a single limb segment. Five patients underwent repeat periosteal release, and one patient had three periosteal releases. Mean follow-up was 63.1 months (SD 33.9). Fifteen patients had sufficient data for statistical analysis. The mean initial absolute discrepancy was 2.01cm (SD 1.13), and the mean initial percentage discrepancy was 4.09% (SD 2.76). The mean final absolute discrepancy was 1.00cm (SD 1.62), and the mean percentage final discrepancy was 1.37% (SD 2.42). The mean reduction in absolute discrepancy was 0.52 cm (95%CI −0.04–1.08; p=0.068, paired t-test), and the mean reduction in percentage discrepancy was 2.00% (95% CI 1.02–2.98, p=<0.001 paired t-test). In five patients the operated limb overgrew the shorter limb. Conclusions. Circumferential periosteal release produces a modest decrease in both absolute and percentage limb-length discrepancy, although the outcome is variable and some patients may experience overgrowth of the operated limb

Many pre-clinical models of atrophic non-union do not reflect the clinical scenario, some create a critical size defect, or involve cauterization of the tissue which is uncommonly seen in patients. Atrophic non-union is usually developed following high energy trauma leading to periosteal stripping. The most recent reliable model with these aspects involves creating a non-critical gap of 1mm with periosteal and endosteal stripping. However, this method uses an external fixator for fracture fixation, whereas intramedullary nailing is the standard fixation device for long bone fractures. OBJECTIVES. To establish a clinically relevant model of atrophic non-union using intramedullary nail and (1) ex vivo and in vivo validation and characterization of this model, (2) establishing a standardized method for leg positioning for a reliable x-ray imaging. Ex vivo evaluation: 40 rat's cadavers (adult male 5–6 months old), were divided into five groups (n=8 in each): the first group was fixed with 20G intramedullary nail, the second group with 18G nail, the third group with 4-hole plate, the fourth group with 6-hole plate, and the fifth group with an external fixator. Tibiae were harvested by leg disarticulation from the knee and ankle joints. Each group was then subdivided into two subgroups for mechanical testing: one for axial loading (n=4) and one for 4-point bending (n=4) using Zwick/Roell® machine. Statistical analysis was carried out by ANOVA with a fisher post-hoc comparison between groups. A p-value less than 0.05 was considered statistically significant. To maintain the non-critical gap, a spacer was inserted in the gap, the design was refined to minimize the effect on the healing surface area. In vivo evaluation was done to validate and characterize the model. Here, a 1 mm gap was created with periosteal and endosteal stripping to induce non-union. The fracture was then fixed by a hypodermic needle. A proper x-ray technique must show fibula in both views. Therefore, a leg holder was used to hold the knee and ankle joints in 90º flexion and the foot was placed in a perpendicular direction with the x-ray film. Lateral view was taken with the foot parallel to the x-ray film. Ex vivo: axial load stiffness data revealed that intramedullary nails are significantly stronger and stiffer than other devices. Bending load to failure showed that 18G nails are significantly stronger than 20G, thus it is used for the in vivo experiments. In vivo: final iteration revealed 3/3 non-union, and in controls with the periosteum and endosteum intact but with the 1mm non-critical gap, it progressed to 3/3 union. X-ray positioning: A-P view in supine position, there was an unavoidable degree of external rotation in the lower limb, thus the lower part of the fibula appeared behind the tibia. To overcome this, a P-A view of the leg was performed with the body in prone rather, this arrangement allowed both upper and lower parts of the fibula to appear clearly in both views. We report a novel model of atrophic non-union, the surgical procedure is relatively simple and the model is reproducible

Aim. Treatment of infected and non-infected non-unions remain a major challenge after orthopedic fracture-related surgery. In clinical practice, several revision surgeries are usually required, including a radical debridement and exchange of implants, to control or even eradicate the infection to finally achieve bone healing. However, a clear treatment algorithm in clinical practice may be difficult to follow due to the heterogeneous patient population. Thus, so controlled settings for research purposes is better achieved in standardized animal studies. So far, there exists no multi-stage animal model that can be realistically transferred to the clinical situation in humans. The importance of such a model is obvious in order to be able to investigate different therapy concepts for infected and non-infected non unions. Methods. In 20 female Sprague-Dawley rats, a critical size defect by a femur osteotomy with 5 mm width was done. The periosteum at the fracture zone was cauterized proximal and distal to the osteotomy to achieve an hypovascularized situation. After randomization, 10 animals were intramedullary infected with a multisensible Staph. aureus strain (10. 3. CFU). After 5 weeks, a second surgery was performed with removing the K-wire, debridement of the osteotomy-gap and re-osteosynthesis with an angle-stable plate. After further 8 weeks all rats were euthanized and underwent biomechanical testing to evaluate bone consolidation or delayed union, respectively. Additional micro-CT analysis, histological, and histomorphometric analysis were done to evaluate bone consolidation or delayed union, respectively, by the score of Lane and Sandhu and to quantify callus formation and the mineralized area of the callus. Results. 5 weeks after the first surgery a non-union had formed in all septic and aseptic animals. According to the Lane and Sandhu score a significantly higher callus formation was found in the infected group. In all infected animals, the inoculated Staph. aureus strain was detected during the revision surgery. 8 weeks after the second surgery no bone healing could be detected in the µ-CT analysis in both groups and biomechanical testing showed a significant lower maximum torque in both groups as compared to the untreated contralateral femura. Conclusion. Here we show first results of a new two-stage pseudarthrosis animal model, which reflects a very realistic clinical situation of an infection-related non-union model. Based on this model, various therapeutic strategies in the treatment of infectious and non-infectious pseudarthrosis, such as the use of bone substitutes, can be evaluated in further studies

A prospective case control study analysed clinical and radiographic results in patients operated on with the periosteum autologous chondrocyte implantation (ACI) due to cartilage lesions on the femoral condyles over 10 years ago. 31 out of the 45 patients (3 failures, 9 non-responders, 2 others) were available for a continuous clinical (Lyshom/Tegner, IKDC, KOOS) and radiographic (Kellgren-Lawrence) follow-up at 0, 2, 5, and 10 years after the ACI procedure. The patients were sub-grouped into focal cartilage lesions (FL) – 10, osteochondritis dissecans (OCD) – 12, and cartilage lesions with simultaneous ACL reconstruction (ACL) – 9 subgroups. Lysholm, Tegner, and IKCD subjective scores revealed stable results over the period from 2 to 10 years with a significant improvement toward the pre-operative levels, but the patients had not reached their pre-injury Tegner levels. KOOS profile at 10 years was: Pain 78.6, Symptoms 78.1, Activities of daily living 82.5, Sports 56.9, and Quality of life 55.1. A 10-year IKDC knee examination classified operated knees as: 14 normal, 10 nearly normal, 5 abnormal and 2 severely abnormal. Kellgren-Lawrence scores of 2 and above were found in 10 patients (FL 5, OCD 0, and ACL 5). Seven patients in the group required an arthroscopic re-intervention (3 ACI related, 4 ACI unrelated). ACI provided safe and stable performance of operated knees over ten years. High incidence of knee osteoarthritis in FL and ACL subgroups, and low incidence in OCD patients indicate that best long performance is expected in localised low-impact cartilage lesions of young patients

The standard approach is through the deltopectoral interval. Among patients with prior incisions, one makes every effort to either utilise the old incision or to incorporate it into a longer incision that will allow one to approach the deltopectoral interval and retract the deltoid laterally. The deltopectoral interval is most easily developed just distal to the clavicle, where there is a natural infraclavicular triangle of fat that separates the deltoid and pectoralis major muscles even in very scarred or stiff shoulders. Typically, the deltoid is retracted laterally leaving the cephalic vein on the medial aspect of the exposure. The anterior border of the deltoid is mobilised from the clavicle to its insertion on the humerus. The anterior portion of the deltoid insertion together with the more distal periosteum of the humerus may be elevated slightly. The next step is to identify the plane between the conjoined tendon group and the subscapularis muscle. Dissection in this area must be done very carefully due to the close proximity of the neurovascular group, the axillary nerve, and the musculocutaneous nerve. Scar is then released from around the base of the coracoid. The subacromial space is freed of scar and the shoulder is examined for range of motion. Particularly among patients with prior rotator cuff surgery, there may be severe scarring in the subacromial space. Internal rotation of the arm with dissection between the remaining rotator cuff and deltoid is critical to develop this plane. If external rotation is less than 30 degrees, one can consider incising the subscapularis off bone rather than through its tendinous substance. For every 1 cm that the subscapularis is advanced medially, one gains approximately 20 to 30 degrees of external rotation. The rotator interval between the subscapularis and supraspinatus is then incised. This release is then continued inferiorly to incise the inferior shoulder capsule from the neck of the humerus. This is performed by proceeding from anterior to posterior with progressive external rotation of the humerus staying directly on the bone with electrocautery and great care to protect the axillary nerve. The key for glenoid exposure as well as improvement in motion is deltoid mobilization, a large inferior capsular release, aggressive humeral head cut and osteophyte removal

There has been a widespread appreciation on the part of both patients and surgeons that pain control following total knee replacement is an important goal. The concepts of both preemptive analgesia and multimodal pain protocols have become increasingly popular. In addition to these ideas, surgeons continue to utilise adjunctive treatments such as peripheral nerve blocks and periarticular injections. Multiple studies demonstrate the efficacy of these therapies. Several authors have published different “cocktails” for their periarticular injections in an attempt to help delineate which components of the cocktail are most important. In addition to deciding on a correct cocktail, how it is delivered is important. This video will demonstrate a technique that increases the likelihood that the injected solution is placed in the appropriate areas and does not simply bath the tissues. Important components of the technique include the use of a small gauge needle (22) and a control syringe to insure proper placement as well as an aim to target the injections into the periosteum of the femur and tibia and the posterior capsule primarily

Alignment of total joint replacement in the valgus knee can be done readily with intramedullary alignment and hand-held instruments. Intramedullary alignment instruments usually are used for the femoral resection. The distal femoral surfaces are resected at a valgus angle of 5 degrees. A medialised entry point is advised because the distal femur curves toward valgus in the valgus knee, and the distal surface of the medial femoral condyle is used as reference for distal femoral resection. In the valgus knee, the anteroposterior axis is especially important as a reliable landmark for rotational alignment of the femoral surface cuts because the posterior femoral condyles are in valgus malalignment, and are unreliable for alignment. Rotational alignment of the distal femoral cutting guide is adjusted to resect the anterior and posterior surfaces perpendicular to the anteroposterior axis of the femur. In the valgus knee this almost always results in much greater resection from the medial than from the lateral condyle. Intramedullary alignment instruments are used to resect the proximal tibial surface perpendicular to its long axis. Like the femoral resection, resection of the proximal tibial surface is based on the height of the intact medial bone surface. After correction of the deformity, ligament adjustment is almost always necessary in the valgus knee. Stability is assessed first in flexion by holding the knee at 90 degrees and maximally internally rotating the extremity to stress the medial side of the knee, then maximally externally rotating the extremity to evaluate the lateral side of the knee. Medial opening greater than 4mm, and lateral opening greater than 5mm, is considered abnormally lax, and a very tight lateral side that does not open at all with varus stress is considered to be abnormally tight. Stability is assessed in full extension by applying varus and valgus stress to the knees. Medial opening greater than 2mm is considered to be abnormally lax, and a very tight lateral side that does not open at all with varus stress is considered to be too tight. Release of tight structures should be done in a conservative manner. In some cases, direct release from bone attachment is best (popliteus tendon); in others, release with pie-crusting technique is safe and effective. In knees that are too tight laterally in flexion, but not in extension, the LCL is released in continuity with the periosteum and synovial attachments to the bone. When this lateral tightness is associated with internal rotational contracture, the popliteus tendon attachment to the femur is also released. The iliotibial band and lateral posterior capsule should not be released in this situation because they provide lateral stability only in extension. The only structures that provide passive stability in flexion are the LCL and the popliteus tendon complex, so knees that are tight laterally in flexion and extension have popliteus tendon or LCL release (or both). Stability is tested after adjusting tibial thickness to restore ligament tightness on the lateral side of the knee. Additional releases are done only as necessary to achieve ligament balance. Any remaining lateral ligament tightness usually occurs in the extended position only, and is addressed by releasing the iliotibial band first, then the lateral posterior capsule, if needed. The iliotibial band is approached subcutaneously and released extrasynovially, leaving its proximal and distal ends attached to the synovial membrane. In knees initially too tight laterally in extension, but not in flexion, the LCL and popliteus tendon are left intact, and the iliotibial band is released. If this does not loosen the knee enough laterally, the lateral posterior capsule is released. The LCL and popliteus tendon rarely, if ever, are released in this type of knee. Finally, the tibial component thickness is adjusted to achieve proper balance between the medial and lateral sides of the knee. Anteroposterior stability and femoral rollback are assessed, and posterior cruciate substitution is done, if necessary, to achieve acceptable posterior stability

Structural bone allografts are a viable option in reconstructing massive bone defects in patients following musculoskeletal (MSK) tumour resection and revision hip/knee replacements. To decrease infection risk, bone allografts are often sterilised with gamma-irradiation, which consequently degrades the bone collagen connectivity and makes the bone brittle. Clinically, irradiated bone allografts fracture at rates twice that of fresh non-irradiated allografts. Our lab has developed a method that protects the bone collagen connectivity through ribose pre-treatment while still undergoing gamma-irradiation. Biomechanical testing of bone pretreated with our method provided 60–70% protection of toughness and 100% protection of strength otherwise lost with conventional irradiation. This study aimed to determine if the ribose-treated bone allografts are biocompatible with host bone. The New Zealand White rabbit (NZWr) radius segmental defect model was used, in which 15-mm critically-sized defects were created. Bone allografts were first harvested from the radial diaphysis of donor female NZWr, and treated to create 3 graft types: C=untreated controls, I=conventionally-irradiated (33 kGy), R=our ribose pretreated + irradiation method. Recipient female NZWr (n=24) were then evenly randomised into the 3 graft groups. Allografts were surgically fixed with a 0.8-mm Kirschner wire. Post-operative X-rays were taken at 2, 6, and 12 weeks, with bony healing assessed by a blinded MSK radiologist using an established radiographic scoring system. The reconstructed radii were retrieved at 12 weeks and analysed using bone histomorphometry and microCT. Kruskal-Wallis and Mann-Whitney tests were utilised to compare groups, with statistical significance when p<0.05. Radiographic analysis revealed no differences in periosteal reaction and degree of osteotomy site union between the groups at any time point. Less cortical remodeling was observed in R and I grafts compared to untreated controls at 6 weeks (p=0.004), but was no longer evident by 12 weeks. Radiographic union was achieved in all groups by 12 weeks. Histologic and microCT analysis further confirmed union at the graft-host bone interface, with the presence of mineralising callus and osteoid. Histomorphometry also showed the bridging external callus originated from host bone periosteum and a distinct cement line between allograft and host bone was present at the union site. Previous studies have shown that the presence of non-enzymatic glycation end products in bone can impair fracture healing. However, these studies investigated bony healing in the setting of diabetic states. Our findings showed that under normal conditions, ribose pretreated grafts healed at rates similar to controls via mechanisms also seen in retrieved human allografts clinically in use. These findings that grafts pretreated with our method are biocompatible with host bone in the rabbit help to further advance this technology for clinical trials

We present our experience of treating 57 cases of bone defects associated with chronic osteomyelitis (COM) and an algorithm for their treatment. A retrospective analysis of our operation database revealed 377 patients treated for COM (2002–2010). 76 (20%) had bone defects, of these 57 had notes and x-rays available. The tibia was most commonly affected (63%), followed by the femur (21%). Infection control procedures included debridement, drilling and sequestrectomy. Long-term antibiotics were seldom used. Prerequisites to reconstruction surgery were; fully healed skin, absence of sequestrae on x-ray and no antibiotics for 2-months. Decision on the method of treatment of defect was made depending on; age, defect size, viability of periosteum and physes, condition of soft tissues and coexisting deformity. Initial treatment was; plaster stabilisation (15), frame stabilisation (6), free fibula structural bone grafts (9), ipsilateral vascularised fibula graft (7), non-structural cancellous bone graft (8), bone transport (8) and amputation (4). Forty three (75%) patients were successfully treated with initial strategy. Initial treatment therefore failed in 14 (25%) patients. Successful treatment subsequently used was; structural bone grafting (6), non-structural bone grafting (4), bone transport (3) and Rush Rod stabilisation (1). Little is known about osteomyelitis-induced bone defects, which cause massive morbidity in developing countries. Our novel research shows that these can be treated successfully, often by relatively simple methods. In the absence of ongoing infection, non-vascularised bone grafting techniques are often successful. Bone transport or vascularised grafting are more reliable but more complex solutions

We present our experience of treating 57 cases of bone defects associated with chronic osteomyelitis (COM) and a new algorithm for their treatment. A retrospective analysis of our operation database revealed 377 patients treated for COM (2002–2010). 76 (20%) had bone defects, of these 57 had notes and x-rays available. Data was collected on: age, sex, type/extent of bone involved, number/type of procedures, and length of stay. The tibia was most commonly affected (63%), followed by the femur (21%). Infection control procedures included debridement, drilling and sequestrectomy. Long-term antibiotics were seldom used. Prerequisites to reconstruction surgery were; fully healed skin, absence of sequestrae on x-ray and no antibiotics for 2-months. Decision on the method of treatment of defect was made depending on; age, defect size, viability of periosteum and physes, condition of soft tissues and coexisting deformity. Initial treatment was; plaster stabilisation (15), frame stabilisation (6), free fibula structural bone grafts (9), ipsilateral vascularised fibula graft (7), non-structural cancellous bone graft (8), bone transport (8) and amputation (4). 43 (75%) patients were successfully treated with initial strategy. Initial treatment therefore failed in 14 (25%) patients. Successful treatment subsequently used was; structural bone grafting (6), non-structural bone grafting (4), bone transport (3) and Rush Rod stabilisation (1). Little is known about osteomyelitis-induced bone defects, which cause massive morbidity in developing countries. Our novel research shows that these can be treated successfully, often by relatively simple methods. In the absence of ongoing infection, non-vascularised bone grafting techniques are often successful. Bone transport or vascularised grafting are more reliable but more complex solutions

Autologous chondrocyte implantation is now a recognised treatment for patients with knee pain secondary to articular cartilage defects. The initial technique involving periosteum as the cover for the implanted cells (ACI-P) has been modified to the use of a type I/III collagen membrane (ACI-C). Matrix-induced Autologous Chondrocyte Implantation (MACI) is a technique in which autologous donor chondrocytes are implanted onto the collagen membrane and then fixed into the defect with fibrin glue. We performed a prospective randomised comparison of 247 patients (126 ACI and 121 MACI). Patients' pain and function were assessed with mean follow-up of 42 months. Function was measured using the Modified Cincinnati and Stanmore Scoring systems. Arthroscopic assessment was by the ICRS classification. The influence of the size and site of the lesion, sex, age and previous knee surgery on the results was analysed. The Modified Cincinnati score showed a mean 17.5 point rise from pre-operative scores in the ACI group and 19.6 point rise in the MACI group. Pain, measured using the Visual Analogue Score, showed an improvement in both arms of the trial. Both chondrocyte implantation methods showed improvement in 86% of patients clinically and arthroscopically, with excellent and good results in 50% and fair results in 30% of patients. 20% of patients showed no improvement in function but none were worse. There were no serious complications. Limited histological analysis showed hyaline cartilage in a higher but non-significant proportion of ACI-C cases. With over 11 years' experience in the use of both forms of cartilage implantation we have established more precisely the indications for chondrocyte implantation. Although MACI is technically a more attractive option in most cases, because of ease and speed of the procedure, longer term follow-up is required to assess the longevity of ACI-C and MACI and the effect on prevention of ‘early-onset’ Osteoarthritis

The key factors in Tissue Engineering are multipotent stem cells, growth factors (necessary to manipulate cell destiny) and scaffolds (3D constructs which support the growing tissue). Mesenchymal stem cells are the most important part of this equation, and it is procurement and manipulation of these that lies at the heart of tissue engineering. Luckily, mensenchymal stem cells can be obtained from many tissues, including synovium, bone marrow and periosteum. The use of bioreactors to optimise culture conditions and improve cell viability provides an opportunity to control stem cell destiny. Various Tissue Engineering strategies exist: manipulating cells in situ with osteogenic growth factors, such as BMP; implanting whole tissue grafts; and the use of Gene therapy. The tissues that concern orthopaedic surgeons are very diverse and no single tissue engineered construct will be able to fulfil all our clinical needs. Tissue engineering of articular cartilage is very difficult technically, but once accomplished will revolutionalise practice. The challenge lies in being able to produce cartilage as similar to native hyaline cartilage as possible. Although promising, ACI, using culture expanded cells, is able at best to produce hyaline-like cartilage but not the real thing. Multipotent mesenchymal stem cells are being used in this field. Even simply injecting these intraarticularly has been shown to retard the progression of OA in animal models. When attempting to regenerate meniscal cartilage, the mechanical properties of the scaffold become crucial, as the biomechanics of the knee are highly hostile. Ligaments and tendons, though the least complex tissues architecturally, have very high tensile properties which will be hard to replicate. The challenging aspects of Orthopaedic Tissue Engineering are manifold, yet the field itself is growing in leaps and bounds. Despite some initial setbacks, the new developments in this discipline are very encouraging

Treatment of large segmental defects in the extremities is challenging. A segmental tibial defect model in a large animal can provide a basis through which in vivo testing of materials and techniques for use in non-unions and severe trauma cases can be examined. This study reports such a model. Six aged ewes (> 5 years) were used following ethical approval. A 5cm piece of the mid diaphysis of the left tibia was removed including its associated periosteum. The tibia was stabilized with an 8mm stainless steel cross locked intramedullary nail and all tissues closed in their respective layers. Animals were euthanised at 12 weeks following surgery and evaluated using radiographic, micro-computed tomography (CT), soft tissue and hard tissue histology techniques. Three weeks post operatively one of the intramedullary nails failed through the first of the distal two cross locking screw holes, the sheep was euthanised and the tibia was harvested. Early signs of callus formation were evident at the osteotomy edges originating from the periosteal surface; the defect space was bridged by fibrous scar tissue. The remaining 5 sheep were taken out to the 12 week time point then all relevant tissues were harvested. Gross dissection revealed a lack of bony union in the defect site and no evidence of infection. X-rays and CT showed a lack of hard tissue callus bridging in the defect region at 12 weeks. Histological sections of the bridging tissues revealed, callus originating from both the periosteal and endosteal surfaces, with fibrous tissue completing the bridging in all instances. One case had cartilaginous tissue developing; however this was incomplete at 12 weeks. As none of the 12 week time point sheep achieved clinical union; this model may be effective as a basis for the investigation of healing adjuncts to be used in non-union cases, where severe traumatic injury has lead to significant bone loss such as blast injuries or following large tumour removal

Introduction and aims. After internal hemipelvectomy for malignant pelvic tumors, pelvic reconstruction is necessary for eventual weight bearing and ambulation. Non-vascularised, fibular grafts (NVFG) offer fast, and stable reconstruction, post- modified Enneking's type I and I/IV resection. This study aimed to evaluate the success of graft union and patient function after NVFG reconstruction. Methods. From 1996 to 2009, 10 NVFG pelvic reconstructions were performed after internal hemipelvectomy in four cases of chondrosarcoma, three of Ewing's sarcoma, and single cases of osteosarcoma, malignant peripheral nerve sheath tumour, and malignant fibrous histiocytoma. A key indication for internal hemipelvectomy was sciatic notch preservation confirmed by preoperative MRI. Operation time and complications were recorded. The mean follow-up was 31.1 months (range: 5 to 56), and lower limb function was assessed using the Musculoskeletal Tumour Society scoring system. Plain radiographs and/or computer tomography were used to determine the presence or absence of NVFG union. Results. The mean operation time was four hours and 56 mins, with no major intraoperative complications and partial wound break-down in only one patient. The NVFG united successfully in all patients, with a mean union time of 7.3 months. Post-operative deep infection did not occur in any case. Seven patients were eventually able to ambulate without a cane, and overall, the average function rating percentage was 75.4%. Recurrent tumour occurred in two cases following primary resection. Death from tumour-related disease occurred in one of the ten cases. Conclusions. NVFG is a stable and reliable pelvic reconstruction method after type I and type I/IV hemipelvectomy. Reliability may be linked to preservation of graft periosteum, and careful patient selection, limited to those with an intact sciatic notch. Furthermore, the relatively short operative time required should help minimise deep infection

In the treatment of ligament injuries there has been much interest in the restoration of the actual ligament anatomy, and the extent to which the original enthesis may be re-established. This study therefore seeks to uncover new information on ligament microstructure and its insertion into bone. Five bovine medial collateral ligaments (MCL) and five ovine anterior cruciate ligaments (ACL) were used in this study. All ligaments were harvested with the femoral and tibial bony insertions still intact. The bone ends were clamped and the MCL stretched to about 10% strain while the ACL underwent a 90° twist. The entire ligament-bone system, under load, was fixed in 10% formalin solution for 12 hours, following which it was partially decalcified to facilitate microsectioning. Thin 30 ìm-thick sections of the ligament-bone interface and ligament midsubstance were obtained. Differential Interference Contrast (DIC) optical microscopy was used to image the ligament and bone microarchitecture in the prescribed states of strain. Fibre crimp patterns were examined for the prescribed loading condition and showed distinct sections of fibre recruitment. Transverse micro-imaging of the ligament showed a significant variation in the sub-bundle cross-sectional area, ranging from 100ìm to 800 ìm. Those bundles closer to the central long axis of the ligament were numerous and small, while moving towards the periphery, they were large and singular. Both classifications of entheses, direct and indirect, were observed in the MCL insertions into the femur and tibia respectively. Of interest was the indirect insertion where the macro-level view of the near parallel attachment of fibres to bone via the periosteum was revealed, at the microscale, to involve a gradually increasing orthogonal insertion of fibres. This unique transition occurred closer to the joint line. In the ACL the anterior-medial (AM) and posterior-lateral (PL) bundles were easily discernable. All insertions into bone for the ACL were of the direct type. Fibres were thus seen to transition through the four zones of gradual mineralization to bone. However the manner in which the AM and PL bundles insert into bone, and the lateral soft tissue transition between these two bundles, revealed a structural complexity that we believe is biomechanically significant. This ‘mechano-structural’ investigation, using novel imaging techniques, has provided new insights into the microstructure of the ligament bone system. The images presented from this study are aimed to aid new approaches for reconstruction, and provide a blue-print for the design of ligament-bone systems via tissue engineering

Bone morphogenetic proteins (BMPs) are able to induce osteogenic differentiation in many cells, including muscle cells. However, the actual contribution of muscle cells to bone formation and repair is unclear. Our objective was to examine the capacity of myogenic cells to contribute to BMP-induced ectopic bone formation and fracture repair. Osteogenic gene expression was measured by quantitative PCR in osteoprogenitors, myoblasts, and fibroblasts following BMP-2 treatment. The MyoD-Cre x ROSA26R and MyoD-Cre x Z/AP mouse strains were used to track the fate of MyoD+ cells in vivo. In these double-transgenic mice, MyoD+ progenitors undergo a permanent recombination event to induce reporter gene expression. Ectopic bone was produced by the intramuscular implantation of BMP-7. Closed tibial fractures and open tibial fractures with periosteal stripping were also performed. Cellular contribution was tracked at one, two and three week time points by histological staining. Osteoprogenitors and myoblasts exhibited comparable expression of early and late bone markers; in contrast bone marker expression was considerably less in fibroblasts. The sensitivity of cells to BMP-2 correlated with the expression of BMP receptor-1a (Bmpr1a). Pilot experiments using the MyoD-Cre x Rosa26R mice identified a contribution by MyoD expressing cells in BMP-induced ectopic bone formation. However, false positive LacZ staining in osteoclasts led us to seek alternative systems such as the MyoD-cre x Z/AP mice that have negligible background staining. Initially, a minor contribution from MyoD expressing cells was noted in the ectopic bones in the MyoD-cre x Z/AP mice, but without false positive osteoclast staining. Soft tissue trauma usually precedes the formation of ectopic bone. Hence, to mimic the clinical condition more precisely, physical injury to the muscle was performed. Traumatising the muscle two days prior to BMP-7 implantation: (1) induced MyoD expression in quiescent satellite cells; (2) increased ectopic bone formation; and (3) greatly enhanced the number of MyoD positive cells in the ectopic bone. In open tibial fractures the majority of the initial callus was MyoD+ indicating a significant contribution by myogenic cells. In contrast, closed fractures with the periosteum intact had a negligible myogenic contribution. Myoblasts but not fibroblasts were highly responsive to BMP stimulation and this was associated with BMP receptor expression. Our transgenic mouse models demonstrate for the first time that muscle progenitors can significantly contribute to ectopic bone formation and fracture repair. This may have translational applications for clinical orthopaedic therapies