Cells typically respond to a variety of geometrical cues in their environment, ranging from nanoscale surface topography to mesoscale surface curvature. The ability to control cellular organisation and fate by engineering the shape of the extracellular milieu offers exciting opportunities within tissue engineering. Despite great progress, however, many questions regarding geometry-driven tissue growth remain unanswered. Here, we combine mathematical surface design, high-resolution microfabrication, in vitro cell culture, and image-based characterization to study spatiotemporal cell patterning and bone tissue formation in geometrically complex environments. Using concepts from differential geometry, we rationally designed a library of complex mesostructured substrates (10. 1. -10. 3. µm). These substrates were accurately fabricated using a combination of two-photon polymerisation and replica moulding, followed by surface functionalisation. Subsequently, different cell types (preosteoblasts, fibroblasts, mesenchymal stromal cells) were cultured on the substrates for varying times and under varying osteogenic conditions. Using imaging-based methods, such as fluorescent confocal microscopy and second harmonic generation imaging, as well as quantitative image processing, we were able to study early-stage spatiotemporal cell patterning and late-stage extracellular matrix organisation. Our results demonstrate clear geometry-dependent cell patterning, with cells generally avoiding convex regions in favour of concave domains. Moreover, the formation of multicellular bridges and collective curvature-dependent cell orientation could be observed. At longer time points, we found clear and robust geometry-driven orientation of the collagenous extracellular matrix, which became apparent with second harmonic generation imaging after ∼2 weeks of culture. Our results highlight a key role for geometry as a cue to guide spatiotemporal cell and tissue organisation, which is relevant for scaffold design in tissue engineering applications. Our ongoing work aims at understanding the underlying principles of geometry-driven tissue growth, with a focus on the interactions between substrate geometry and mechanical forces

This study aims to evaluate the development of deformity in patients with hypophosphataemic rickets and the evolution of the orthopaedic management thereof. Fifty-four patients had undergone treatment for hypophosphataemic rickets at our institution since 1995. Clinical records for all patients were obtained. Forty-one patients had long leg radiographs available that were analysed using Traumacad™ software. Statistical analysis was performed using SPSS 23 (SPSS Inc., Chicago, Illinois, USA). Of the 41 patients, 18 (43%) had no radiographic deformity. 20 have undergone bilateral lower limb surgery for persistent deformity (Mechanical Axis ≥ Zone 2). A further 3 patients are awaiting surgery. Six patients (12 limbs, 14 segments) had osteotomies and internal fixation as primary intervention: only one limb developed recurrent deformity. There were no major complications. Fourteen patients (28 limbs) had 8-plates (Orthofix, Verona) applied. In 5 limbs correction is on-going. Neutral alignment (central Zone 1) was achieved in 14/20 (70%) patients. Two patients required osteotomy and external fixation for resistant deformity. The mean rate of angular correction following 8-plate application was 0.3 and 0.7 degrees/month for the tibia and femur respectively. The mean age at 8-plate insertion was 10.25y (5–15y). Patients with more than 3 years of growth remaining responded significantly better than older patients (Fisher Exact Test, p=0.024). Guided growth was more successful in correcting valgus deformity than varus deformity (Fisher Exact Test, p=0.04). In the younger patients, diaphyseal deformity corrected as the mechanical axis improved at the rate of 0.2 and 0.7 degrees /month for the tibial and femoral shafts. Serum phosphate and alkaline phosphatase levels did not affect response to surgery or complication rate. Guided growth by means of 8-plates is a successful in addressing deformity in hypophosphataemic rickets. Surgery is best performed in patients with more than 3 years of growth remaining

Purpose: Rigid full-time braces are the most common non-surgical treatment for adolescents with moderate severity of scoliosis and demonstrated growth remaining. The Scoliosis Research Society (SRS) has established guidelines on which patients with adolescent idiopathic scoliosis (AIS) should be offered brace treatment. This study surveyed Canadian surgeons on the demographics of patients with scoliosis attending specialty clinics and for their protocols for prescribing braces. Method: An on-line survey of 41 questions was developed to document patient profiles and surgeon protocols for prescribing braces. Surgeons also selected whether they would recommend a brace in females with AIS based on a combination of three levels of maturity, with six levels of curve severity, and whether or not the curve was progressive. The survey was administered between July and November 2008 to the 30 paediatric spine surgeon members of the Canadian Paediatric Spinal Deformities Study Group. After one reminder, the response rate was 70% (21/30), representing 12 Canadian spine centres. Results: The average age of referral to the scoliosis clinic was 11–12 years (10 of 20 respondents) and 13–14 years (nine of 20 respondents). Most (81%) of the centers required radiographs prior to the first clinic visit. All surgeons recommended bracing, but there was broad variation on who they considered should be braced, with three to twenty six of the 36 potential scenarios defined by maturity, progression, and curve severity variables selected. This high variability was also observed among surgeons in the same spine centre. All considered parental or family issues and patient acceptance when recommending a brace. Age and curve severity were criteria for bracing; skeletal maturity was the primary criteria for discontinuing bracing. The majority (81%) of braces prescribed were rigid full-time braces followed by rigid night-time braces (14%). Weaning was common (76%), but protocols varied. Detection of curve progression increased the likelihood of bracing for curves 80% agreement on bracing. Braces were not recommended by > 50% of respondents for females with less than 1 year growth remaining regardless of progression or curve size. Conclusion: In spite of SRS guidelines and general agreement that braces are effective, there is little agreement among surgeons on which females with AIS should receive brace treatment. The likelihood that a female with AIS will be prescribed brace treatment primarily depends on surgeon brace prescription patterns, rather than actual curvature of the spine

Background: Lower limb buds appear during the second week of embryonic life and are well differentiated by the end of the 8th week. Primary ossification centres of femur and tibia appear by the end of the 8th week and by 12 weeks the cartilaginous anlage is complete. By 14 weeks primary ossification is sufficient to allow accurate ultrasonographic measurement of femoral length. There are many established database for estimating fetal femoral length ultrasonagraphically. There is little data however on radiological measurements of fetal femoral lengths. The aim of our study was to introduce radiologically measured fetal femoral lengths in order to improve our understanding of normal fetal femoral growth. Methods: A group of 40 post-mortem foetal radiographs ranging from 14 weeks to 39 weeks gestation were retrieved from our radiology department having excluded all cases with associated lower limb deformation. Femoral lengths were measured and plotted against gestational age. A standard growth curve was constructed and compared to the currently available data on ultrasonographic measurements. A growth velocity chart, growth remaining and an antenatal multiplier chart was also constructed. Results: At 14 weeks the length of the femur was 14mm and the tibia 11mm. At birth the femoral diaphyseal length was 75mm and the tibia 62mm. Using the standard growth curve there was a strong correlation between our radiological measurements and previously published ultrasonographic measurements (R2= 0.9492). The femoral growth velocity curve demonstrated a rapid growth acceleration phase peaking at 12 cm/annum at 16 weeks, followed by a rapid deceleration phase reducing to a growth rate of 5 cm/annum at birth. The growth remaining was calculated for each week. At 24 weeks the growth achieved is 10% thus giving a multiplying factor of 10. At birth the growth achieved is 20% giving a multiplying factor of 5. Discussion: Modern 3D and 4D ultra-sonography has lead to an increasingly accurate detection of antenatal deformities. Antenatal orthopaedics is an advancing sub-specialty. The understanding of normal intra-uterine growth is essential knowledge of a paediatric orthopaedic surgeon when advising on antenatally detected deformities. This correlation of ultrasonographic and radiographic measurements further deepens our understanding of foetal femoral growth

Introduction: Percutaneous epiphyseodesis is a simple method of achieving leg length equality in cases of minor leg length discrepancy, however few studies document its effectiveness. A retrospective study was undertaken to assess this. Materials and methods: Patient notes and radiographs were reviewed. The growth remaining method was used to estimate timing. Percutaneous epiphyseodesis was performed with a drill and curette under radiological guidance. Results: A total of 24 skeletally mature patients with a mean preoperative leg length discrepancy (LLD) of 2.8cm were identified. Skeletal age was significantly different from chronological age in 5 of 11 cases where it had been performed. In all patients, there was radiographic evidence of physeal closure soon after epiphyseodesis. At skeletal maturity, 14 patients have a LLD of 0–1cm and are considered to have a satisfactory outcome. 10 patients have a LLD> 2cms. In 6 of these, either presentation was too late or the amount of discrepancy too large for complete correction to be expected. In the other 4, skeletal age assessment may have been useful in 3, and in one additional case of overgrowth of the short limb prior to maturity. A successful outome was more likely when skeletal age assessment had been used (82% versus 57%). Of the 18 cases where there was sufficient time for a full correction to be achieved, the overall success rate was 72%. There were no significant clinical or radiological complications. Conclusions:. Percutaneous drill epiphyseodesis is an effective method of achieving physeal ablation with no significant complications. While the growth remaining method is a crude estimate of the timing of epiphyseodesis, it was accurate in the majority of cases in this small series. The determination of skeletal age was found to be a useful adjunct to management in a small proportion of cases

Primary malignant bone tumours frequently arise in children close to the knee, hip or shoulder. Resection of the tumour will often require excision of the epiphysis and frequently one side of the involved joint. In these children an extendable endoprosthesis is usually required to allow for maintenance of limb length equality. We have used 180 extendable endoprostheses in 176 children since 1975. The indication for use of an extendable prosthesis was if there was more than 30mm of growth remaining in the resected bone. The age of the patients ranged from 2 to 15 and 99 were boys. The sites of the endoprostheses used were: distal femur in 91, proximal tibia in 42, proximal femur in 11, total femur in 6 and proximal or total humerus in 26. 131 of the operations were for osteosarcoma and 34 for Ewing's. Five types of lengthening mechanism have been used. Two designs used a worm screw gear, one type used a C collar, one type a ball bearing mechanism and the latest uses a non invasive lengthening system whereby a motor inside the prosthesis is activated by an electromagnetic field. Of the 176 patients, 59 have died and of the remainder, 89 have reached skeletal maturity. 19 patients had an amputation, 11 due to local recurrence and 8 due to infection. The risk of infection was 19% in surviving patients. Most of the skeletally mature had equal leg lengths. The average number of operations was 11 but ranged between 2 and 29. Most operations were for lengthening but younger children always needed revisions of the prosthesis. Functional scores were 77%. Extendable endoprostheses are demanding both for the patient and the surgeon. The high complication rate should be decreased by non invasive lengthening prostheses

Introduction and Aims: Rotationplasty is a functional alternative to above knee amputation in very young patients with a lot of growth remaining and patients with large tumors necessitating excision of the thigh musculature. The development of gait following rotationplasty surgery was studied with serial gait and clinical analysis. Method: Five patients have been reviewed using three dimensional gait analysis incorporating temporal and spatial measures. A gait analysis was performed after the initial prosthetic fitting, six and 12 months postoperatively. The gait analysis included velocity, temporal/spatial measurements (velocity, cadence, step/stride length, pedobarographs), optical tracking and electromyography. Results: The kinematic and kinetic data revealed the rapid incorporation of knee flexion/extension (ankle dorsi/plantar flexion) into the gait cycle. Electromyography also showed the gastrocnemius to be simulating the quadriceps and the tibialis anterior to mimic the hamstrings in terms of firing time in the stance and swing phase of the rotated limb. Propulsive forces on the kinetic analysis suggest further gait maturation can occur for several years following this procedure. Conclusion: Children adapt very well to the altered anatomy following rotationplasty and using gait analysis confirms the new role of the altered muscles. Weakness about the hip remains a major concern that needs to be addressed with physiotherapy for several years postoperatively

Summary Statement. Extended expansion of cells derived from equine articular cartilage reveal maintenance of chondrogenic potency and no evidence of senescence up to 100 population doublings. The data suggests the reclassification of these cells from progenitor cells to stem cells. Introduction. One sign of ‘in vitro aging’ is the diminishing capacity for cell division. In contrast to embryonic stem cells that show no loss of proliferative potency, the maximal population doublings (PD) for mesenchymal stem cells (MSCs) in vitro is reported to be between 30 and 40 replications 1,2,3. We have isolated a population of chondroprogenitor cells from articular cartilage of several species, including equine4. These cells have demonstrated functional equivalence in their differentiation capacity when compared with MSCs but have the advantage of retaining the highly desirable stable (permanent) chondrocyte phenotype. In this study, we examined the age-related capacity of these cells for extended division and retention of potency. Methods. Chondroprogenitors were isolated from equine articular cartilage by adhesion onto fibronectin5. Cells were isolated from both skeletally immature (1 year-old) and mature animals (8 year-old). Clonal and polyclonal cell lines (at least 5 of each for each age) were cultured in the presence of 10% FCS, 1ng/ml TGFb-1 & 2.5 ng/ml FGF-2. Cells were seeded at low density and passaged weekly. Results. Chondroprogenitors from both animals reached over 40 (mean) PD in 50 days with growth remaining linear. Little difference in growth rates was observed between clonal and polyclonal cell lines. For the mature animal, 96% of cells were BrDU positive at 22 PD whilst none of cells were (senescence associated) β-gal positive. At 44 PD, 88% of cells were BrDU positive and just 15% of cells were β-gal positive. Three clonal and three polyclonal cell lines from the mature animal were cultured beyond the 50-day time point. At 120 days, cells reached up to 90 PD with the same pattern of linear growth observed. When tested at 70 PD, 79% of these cells were still BrDU positive (range 55–97%) and just 11% of cells were β-gal positive (range 2–22%). Furthermore, little difference in cell morphology was observed throughout this extended expansion. At 70 PD, we found that both clonal and polyclonal cell lines in monolayer culture were still expressing the chondrogenic transcription factor; Sox-9. Expression of genes for aggrecan and collagen type II was also detected in cells that were chondrogenically induced for 72 hours. Discussion & Conclusions. We have demonstrated for the first time the extended expansion of cells derived from articular cartilage that retain chondrogenic potency. These equine cells have since been cultured to over 100 PD without evidence of senescence. One hundred PD is equivalent to 1 × 1030 cells originating from a single cell. We have previously reported that the human equivalents of these cells surpass MSCs in doubling capacity but senesce at approximately 60 PD6. The properties of these equine chondroprogenitor cells make them ideal candidates for allogeneic cell therapy for articular cartilage repair. In addition, the data suggest the reclassification of these cells from progenitor cells to stem cells

Introduction. Idiopathic scoliosis is a lateral curvature of the spine >10° as measured on a frontal plane radiograph by the Cobb angle. Important variables in assessing the risk of curve progression include a young age at presentation, female sex, a large amount of growth remaining, the rate of growth, the curve magnitude, and the curve location. Curves >20° have an inherently low risk of progression. Surgery is indicated for curves >50° or rapidly progressing curves. The timing of surgery is paramount in order to intervene in cases where rapid progression is evident to prevent further deterioration. There is a greater likelihood for more complex surgery to be required in major curves. At present, there are severe restrictions on resources to cater for patients with scoliosis. As a result, patients spend excessive periods on waiting lists prior to having their procedure. The aim of this study is to analyse the progression of curves of patients while on the waiting list and assess the cost implications of curve deterioration. Methods. A retrospective analysis of 40 cases of adolescent idiopathic scoliosis performed from between 2007-2010 was carried out. All radiographs at the time of being placed on the waiting list and the time of admission were reviewed to assess the Cobb angle. The radiographs were analysed independently by three spinal surgeons to determine what level of surgical intervention they would recommend at each time point. The final procedure performed was also recorded. A cost analysis was carried out of all of the expenses that are incurred as part of scoliosis surgery, including length of hospital stay, intensive care admission, spinal monitoring, implant cost, and the requirement for multiple procedures. Results. The average time on the waiting list was 12 months (range 6 – 16 months). Comparison of radiographs at the time of listing and time of admission revealed a deterioration of the Cobb angle by an average of 12°. The average Cobb angle at time of surgery was 78° (range 55° - 96°). Analysis of cost implications revealed an increase in cost based on implant requirements, length of stay and intensive care admission estimated at 25%. Conclusion. The results of this study demonstrate that there is a significant deterioration of scoliosis curvature in patients while on the waiting list. The consequence of this progression results in longer operative time, increased requirement for intensive care beds, an increase in requirements for additional levels of pedicle instrument, and a prolonged length of stay. The implications of the deterioration in curvature result in an increase in overall cost estimated at 25%. Waiting list initiatives established over the past 6 months have reduced the waiting list to 6-9 months. Further efforts to continue this initiative are likely to give rise to further cost reductions and result in more manageable curvatures being dealt with in a timely fashion

In the last decades the number of anterior cruciate ligament (ACL) injury in skeletally immature patients (SIP) increased as a result of the participation in competitive sports at younger age and improved diagnostic tools allowing early diagnosis of ACL injury. Although the eminence avulsion fracture is more frequent in SIP and considered the ACL injury pediatric equivalent, intra-substance ACL injury in children is a growing problem. With torn ACL injured knee remains unstable. This instability is poorly tolerated in teens since it is difficult to limit their activity and leads to meniscal and chondral tears and causes resignation from sport carrier. Intraarticular transphyseal ACL reconstruction seems to be effective technique to restore knee stability despite potential iatrogenic complications such as epiphisiodesis, leg length discrepancy and axial malalignment. The main aim of this study was to evaluate the efficacy and results of this method and assess frequency of potential complications. Material: From 2006 to 2007 we performed 15 reconstructions (7 boys, 8 girls) of ACL in skeletally immature patients (Tanner 3). All patients were athletes. Average age of girls was 11,2 years and boys 12,3 years. The period from injury to reconstruction were shorter than 10 months. All patients were operated by the same surgeon using the same surgical technique – gracilis-semitendinosus autograft, with transphyseal tibial and femoral tunnels and extraarticular fixation with AO screws. Average tunnel diameter was 7 mm. All beside one ACL injuries were isolated, with 1 meniscus tear. Methods: In prospective study without control group patients were examined before reconstruction, and 6, 12, 24 months after surgery IKDC, Lysholm and Tegner score. We assessed the growth, leg length and axial disturbances by clinical and radiological assessment and the return to prior level of sport activity. Results: In 12 and 24 months follow-up no disturbance of angular and longitudinal growth were observed, 11/12 patients returned to previous sport activity after mean of 7 months post- op with scores: IKDC 96,5 after 12 months and 97 after 24 months, Lysholm 95 after 12 months and 96 after 24 months. Average gain of growth was 5,5cm/12 months on average. Conclusion: The use of complete transphyseal reconstruction is a safe, reliable technique in patients who have significant growth remaining, providing adequate knee stability, good satisfaction and allowing return to sport activity

Despite biomechanical well established implants and improved operation techniques we still have a too high rate of complications in orthopaedic and trauma surgery like non-union, implant loosening or implant associated infections. The development of bioactive implants could improve the clinical outcome. Growth factors are important regulators of bone metabolism. During fracture healing many growth factors or cytokines were locally released at the facture site. In several studies, different growth factors demonstrated osteoinductive and fracture stimulating properties. In vitro and in vivo studies showed a stimulating effect of Insulin-like growth factor-I (IGF-I), Transforming growth factor-A71 (TGF-A71) and Bone morphogenetic protein-2 (BMP-2) on osteo- and chondrogenetic cells. The exact effectiveness and the interaction of these growth factors during fracture healing is not known so far. Further, the local application of these factors for therapeutically use in fracture treatment is still a problem. A biodegradable poly(D,L-lactide)-coating of implants allows the local and controlled release of incorporated growth factors directly at the fracture site. The coated implant serves on the one hand for fracture stabilization and on the other hand as a drug delivery system. The coating has a high mechanical stability. The incorporated growths factors remain biologically active in the coating and were released in a sustained and controlled manner. To investigate the effect of locally released growth factors IGF-I, TGF-A71 and BMP-2 and the carrier PDLLA on fracture healing, standardised closed fracture models were developed with a close relationship to clinical situation. Further, possible local and systemic side effects were analysed. The results demonstrated a significantly higher stimulating effect of IGF-I on fracture healing compared to TGF-A71. The combined application of both growth factors showed a synergistic effect on the mechanical stability and callus remodeling compared to single treatment. The local release of BMP-2 also enhanced fracture healing significantly – comparable to combination of IGF-I and TGF-A71. However, a higher rate of mineralisation was measurable outside the fracture region using BMP-2 in a rat fracture model. Using a large animal model on pigs with a 1 mm osteotomy gap, the effectiveness of locally released growths factors could be confirmed. Further, the PDLLA-coating without any incorporated growth factors demonstrated a significantly effect on healing processes in both models. These investigations showed, that the local release of growth factors from PDLLA coated implants significantly stimulate fracture healing without any local or systemic side effects. Comparing systemic with local stimulation techniques, we found an improvement of fracture healing by systemic administration of growth hormone and local application of IGF-I and TGF-A71. However, the combined use of both simulation techniques did not lead to a further increase of healing processes. Investigations on the effectiveness and the interaction of growth factors during fracture healing demonstrated an dramatic effect in the early phases of healing processes. The growth factors stimulate the differentiation of osteoblasts with a higher production of collagen I in vitro and increase osteogenesis and vascularisation of the fracture callus in vivo. Further applications of the coating technology are the use of PDLLA and growth factor coated cages for the stimulation of intervertebral fusion and the use of PDLLA and Gentamicin coated implants in order to prevent implant associated infections. The first patients with open tibia fractures were treated with PDLLA and Gentamicin coated IM nails

Objectives

We have observed clinical cases where bone is formed in the overlaying muscle covering surgically created bone defects treated with a hydroxyapatite/calcium sulphate biomaterial. Our objective was to investigate the osteoinductive potential of the biomaterial and to determine if growth factors secreted from local bone cells induce osteoblastic differentiation of muscle cells.

The October 2013 Children’s orthopaedics Roundup³⁶⁰ looks at: Half a century of Pavlik treatment; Step away from the child!: trends in fracture management; Posterolateral rotatory elbow instability in children; Osteochondral lesions undiagnosed in patellar dislocations; Oral bisphosphonates in osteogenesis imperfecta; Crossed or parallel pins in supracondylar fractures?; Not too late nor too early: getting epiphysiodesis right; Fixation of supramalleolar osteotomies.