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Articular cartilage (AC) is a seemingly simple tissue that has only one type of constituting cell and no blood vessels and nerves. In the early days of tissue engineering, cartilage appeared to be an easy and promising target for reconstruction and this was especially motivating because of widespread AC pathologies such as osteoarthritis and frequent sports-induced injuries. However, AC has proven to be anything but simple. Recreating the varying properties of its zonal structure is a challenge that has not yet been fully answered. This caused the shift in tissue engineering strategies toward bioinspired or biomimetic approaches that attempt to mimic and simulate as much as possible the structure and function of the native tissues. Hydrogels, particularly gradient hydrogels, have shown great potential as components of the biomimetic engineering of the cartilaginous tissue.

Articular cartilage (AC) is a seemingly simple tissue that has only one type of constituting cell and no blood vessels and nerves. In the early days of tissue engineering, cartilage appeared to be an easy and promising target for reconstruction and this was especially motivating because of widespread AC pathologies such as osteoarthritis and frequent sports-induced injuries. However, AC has proven to be anything but simple. Recreating the varying properties of its zonal structure is a challenge that has not yet been fully answered. This caused the shift in tissue engineering strategies toward bioinspired or biomimetic approaches that attempt to mimic and simulate as much as possible the structure and function of the native tissues. Hydrogels, particularly gradient hydrogels, have shown great potential as components of the biomimetic engineering of the cartilaginous tissue.

Background: Femoral shaft fractures, typical in younger people, are often associated with polytrauma followed by traumatic shock. In these situations, despite intramedullary nailing being the treatment of choice, external fixation could be used as the definitive treatment. The aim of this study is to report evidence regarding definitive treatment of femoral shaft fractures with monoaxial external fixation. Methods: Between January 2006 and December 2015, 83 patients with 87 fractures were treated at the Department of Orthopaedics and Traumatology CTO of Turin, with a monoaxial external fixation device. Mean age at surgery, type of fracture, mean follow-up, time and modalities of treatment, non-weight bearing period, average healing, external fixation removal time, and complications were reported. Results: The average patient age was 31.43±15.19 years. In 37 cases (42.53%) the right femur was involved. 73 (83.91%) fractures were closed, and 14 (16.09%) were open. The average follow-up time was 61.07±21.86 weeks. In 68 (78.16%) fractures the fixation was carried out in the first 24 hours, using a monoaxial external fixator. In the remaining 19 cases, the average delay was 6.80±4.54 days. Mean non-weight bearing time was 25.82±27.66 days (ranging from 0 to 120). The 87 fractures united at an average of 23.60±11.37 weeks (ranging from 13 to 102). The external fixator was removed after an average of 33.99±14.33 weeks (ranging from 20 to 120). Reported complications included 9.19% of delayed union, 1.15% of septic non-union, 5.75% of malunion, and 8.05% cases of loss of reduction. Conclusions: External fixation of femoral shaft fractures in polytrauma is an ideal method for definitive fracture stabilization, with minimal additional operative trauma and an acceptable complication rate.

The concept of a post-natal “mesenchymal stem cell” (“MSC”) originated from studies focused on bone marrow stromal cells (BMSCs), which are non-hematopoietic adherent cells, a subset of which are skeletal stem cells (SSCs), able to form cartilage, bone, hematopoiesis-supportive stroma, and marrow adipocytes based on rigorous clonal and differentiation assays. Subsequently, it was speculated that BMSCs could form other mesodermal derivatives and even cell types from other germ layers. Based on BMSC surface markers, representative of fibroblastic cells, and imprecise differentiation assays, it was further imagined that “MSCs” are ubiquitous and equipotent. However, “MSCs” do not have a common embryonic origin and are not a lineage, but recent studies indicate that they are tissue-specific stem/progenitor cells. These cells share cell surface features owing to their fibroblastic nature, but they are not identical. They display different differentiation capacities based on their tissue origin but do not “trans-differentiate” outside of their lineage, based on rigorous assays. For these reasons, the “MSC” term should be abandoned. Tissue-specific stem/progenitor cells provide the opportunity to devise methods for tissue regeneration by the cells themselves (tissue engineering). Their use in other forms of regenerative medicine based on paracrine, immunosuppressive, and immunomodulatory effects is far less clear.

For decades, researchers have been fascinated by the strategy of using cell therapy for bone defects; some progress in the field has been made. Owing to its ample supply and easy access, skin, the largest organ in the body, has gained attention as a potential source of stem cells. Despite extensive applications in skin and nerve regeneration, an increasing number of reports indicate its potential use in bone tissue engineering and regeneration. Unfortunately, few review articles are available to outline current research efforts in skin-based osteogenesis. This review first summarizes the latest findings on stem cells or progenitors in skin and their niches and then discusses the strategies of skin cell-based osteogenesis. We hope this article elucidates this topic and generates new ideas for future studies.

Objective: Anterior odontoid screw fixation for type II odontoid fracture is the ideal management option. However in the context of unavailability of an O-arm or neuro-navigation and poor images from the available C-arm may be an obstacle to ideal trajectory and placement of the odontoid screw. We herein detail our surgical technique so as to ensure a correct trajectory and subsequent good fusion in Type II odontoid fractures. This may be advantageous in clinical set ups lacking state of the art facilities. Methods and Results: In this cohort study we included 15 consecutive patients who underwent anterior odontoid screw placement. We routinely dissect the longus colli to completely visualize the entire width of C3 body. We then perform a median C2-C3 disectomy followed by creating a gutter in the superior end of C3 body. We then guide the Kirchsner (K) wire purchasing adequate anterior cortex of C2. Rest of the procedure follows the similar steps as described for odontoid screw placement. We achieved 100% correct trajectory and screw placement in our study. There were no instances of screw break out, pull out or nonunion. There was one patient mortality following myocardial infarction in our study. Conclusion: Preoperative imaging details, proper patient positioning, meticulous dissection, thorough anatomical knowledge and few added surgical nuances are the cornerstones in ideal odontoid screw placement. This may be pivotal in managing patients in developing nations having rudimentary neurosurgical set up.

Regional anaesthesia provides effective anaesthesia and analgesia in the perioperative setting. Central neuraxial blocks—that is, spinal and epidural blocks—are well established as an alternative or adjunct to general anaesthesia. Peripheral blocks may be used as part of multimodal anaesthesia/analgesia in perioperative practice, reducing the need for opioid analgesics and enhancing early recovery. Furthermore, regional anaesthesia has increased in popularity and may be done with improved ease and safety with the introduction of ultrasound-guided techniques. The effects of local anaesthetics and regional anaesthesia on long-term outcomes such as morbidity, mortality, the quality of recovery beyond the duration of analgesia, and whether it can expedite the resumption of activities of daily living are less clear. It has also been suggested that regional anaesthesia may impact the risk of metastasis after cancer surgery. This article provides an overview of current evidence around quality of recovery, risk for delirium, long-term effects, and possible impact on cancer disease progression associated with the clinical use of local and regional anaesthetic techniques. In summary, there is still a lack of robust data that regional anaesthesia has a clinical impact beyond its well-acknowledged beneficial effects of reducing pain, reduced opioid consumption, and improved quality of early recovery. Further high-quality prospective studies on long-term outcomes are warranted.

The treatment of hip fractures in the elderly represents a major public health priority and a source of ongoing debate among orthopaedic surgeons and anesthesiologists. Most of these injuries are treated with surgery in an expedient fashion. From the surgical perspective, there are certain special considerations in this population including osteoporosis, pre-existing arthritis, age, activity level, and overall health that contribute to the type of surgical fixation performed. Open reduction and internal fixation versus arthroplasty remain the two major categories of treatment. While the indications and treatment algorithms still remain controversial, the overall goal for these patients is early mobilization and prevention of morbidity and mortality. The use of preoperative, regional anesthesia has aided in this effort. The purpose of this review article is to examine the various treatment modalities for hip fractures in the elderly and discuss the most recent evidence in the face of a rapidly aging population.

Objective: Anterior odontoid screw fixation for type II odontoid fracture is the ideal management option. However in the context of unavailability of an O-arm or neuro-navigation and poor images from the available C-arm may be an obstacle to ideal trajectory and placement of the odontoid screw. We herein detail our surgical technique so as to ensure a correct trajectory and subsequent good fusion in Type II odontoid fractures. This may be advantageous in clinical set ups lacking state of the art facilities. Methods and Results: In this cohort study we included 15 consecutive patients who underwent anterior odontoid screw placement. We routinely dissect the longus colli to completely visualize the entire width of C3 body. We then perform a median C2-C3 disectomy followed by creating a gutter in the superior end of C3 body. We then guide the Kirchsner (K) wire purchasing adequate anterior cortex of C2. Rest of the procedure follows the similar steps as described for odontoid screw placement. We achieved 100% correct trajectory and screw placement in our study. There were no instances of screw break out, pull out or nonunion. There was one patient mortality following myocardial infarction in our study. Conclusion: Preoperative imaging details, proper patient positioning, meticulous dissection, thorough anatomical knowledge and few added surgical nuances are the cornerstones in ideal odontoid screw placement. This may be pivotal in managing patients in developing nations having rudimentary neurosurgical set up.

Blount’s disease is a progressive form of genu varum due to asymmetrical inhibition of the postero medial portion of the proximal tibial epiphysis. The surgical treatments involved in correction of Blount’s disease are often technically demanding, complicated procedures. These procedures can lead to prolonged recovery times and poor patient compliance. In such a context we are suggesting “fibulectomy with Z osteotomy” of the proximal tibia, a relatively simple and highly effective technique. This technique is based on correcting the mechanical axis of the lower limb thereby restoring growth from the medial physis of proximal tibia. We have used a new surgical technique, which includes fibulectomy followed by a Z-shaped osteotomy. We have used this simple technique in a 5 year-old boy with unilateral Blount’s disease. The femoro-tibial angle was corrected from 18.2° of varus to 4.2° of valgus. The angular correction obtained after operation was 22°. There were no postoperative complications. This technique has the advantages of correcting both angular and rotational deformities simultaneously. The purpose of this case study is to introduce a new surgical technique in the treatment of Blount’s disease.

Introduction: Accurate femoral prosthesis press-fit is essential for successful cementless total hip arthroplasty (cTHA) and dependent upon proximal femur size and geometry. Study objectives were to determine the variability of proximal femur size and geometry in primary cTHA patients and correlate them with patient demographics and body mass index (BMI). Methods: Medical records of 127 consecutive primary cTHA patients were reviewed retrospectively. The demographic (ethnicity, sex, age) and BMI data were collected. Intertrochanteric (IT) distance, inner/outer proximal femur diameters and cortical thickness for the subtrochanteric (ST) and cortical diaphyseal (DP) regions were measured from anteroposterior radiographs. Descriptive statistics were used to correlate patient demographics and BMI with radiographic measurements. Results: The study included 96 cTHA patients (mean age 60 years, range 22-91 years; 34 females; 72 Caucasian, 18 Black, and six Hispanic) with four underweight; 13 normal; 34 overweight, and 45 obese BMI. No correlation existed for patient age or race with radiographic measurements. Males had significantly larger proximal femur dimensions and cortical thickness than females. No BMI correlations existed for IT distance; BMI was directly proportional to outer diameter and cortical thickness in ST and DP regions, and inversely proportional to inner diameter in these regions. Discussion: Greater proximal femur size appears to correlate with gender, but not with age or race. Larger subtrochanteric and diaphyseal outer diameters are significantly associated with higher BMI. A trend exists for larger subtrochanteric and diaphyseal inner diameters to be associated with lower BMI. These findings may have implications for optimal cTHA femoral component design.

Objective: This case report presents the orthopaedic impact of arthrochalasia-type Ehlers-Danlos syndrome (EDS) (former type VIIA and B) in a young girl. Methods: The characteristics of EDSs are skin abnormalities and tissue fragility with orthopaedic consequences including joint hypermobility and dislocations. In EDS arthrochalasia type (former type VIIA and B) severe general hypotonia and congenital bilateral hip dislocation are distinctive symptoms. This type of EDS is less common than other types and just a few cases have been reported. Results: This report describes a case of a 3-year old girl with EDS arthrochalasia type and bilateral high hip dislocation, spontaneous shoulder dislocation and scoliosis as orthopaedic consequences. Conclusions: Orthopaedic consequences in these cases can be severe so conservative or surgical treatment will be necessary to reduce disability in later life. Timing of either conservative or surgical intervention is essential. According to the literature, most conservative treatments fail. Also, surgical treatment is rarely effective in most of the cases. Both conservative and surgical treatment should be considered carefully in the treatment of EDS arthrochalasia type, each of which has pros and cons. The best treatment depends on the prognosis and current situation of the child.

Background: Arthroscopic shoulder surgery is increasingly performed as a day case procedure. Optimal post-operative pain relief remains a challenge due to considerable variations in the level of pain experienced between individuals. Our aim was to examine whether the preoperative electrical pain threshold was a strong predictor of elevated postoperative pain levels following arthroscopic subacromial decompression (ASD) surgery. Methods: Forty consenting patients with American Society of Anesthesiologists (ASA) grade 1-2 presenting for elective ASD surgery were recruited. Patients’ electrical pain thresholds were measured preoperatively using a PainMatcher® (Cefar Medical AB, Lund, Sweden) device. Following surgery under general anaesthesia, the maximum pain experienced at rest and movement was recorded using a visual analogue scale until the end of postoperative day four. Results: In univariate analyses (t-test), the postoperative pain experienced (Area Under Curve) was significantly greater in patients with a low pain threshold as compared with a high pain threshold at both rest (mean 12.5, S.E. 1.7 v mean 6.5, S.E.1.2. P=0.008) and on movement (mean 18.7, S.E. 1.5 v mean 14.1, S.E.1.4. P=0.031). In multivariate analyses, adjusting for additional extra analgesia, the pain experienced postoperatively was significantly greater in the low pain threshold group both at rest (mean difference 4.9, 95% CI 1.5 to 8.4, P=0.007) and on movement (mean difference 4.1, 95%CI 0.03 to 8.2, P=0.049). Conclusions: Preoperative pain threshold can predict postoperative pain level following ASD of the shoulder. Trial registration: Clinicaltrials.gov identifier: NCT01351363 Level of Evidence: II

Human mesoangioblasts are currently in a phase I/II clinical trial for the treatment of patients with Duchenne muscular dystrophy. However, limitations associated with the finite life span of these cells combined with the significant numbers of mesoangioblasts required to treat all of the skeletal muscles in these patients restricts their therapeutic potential. Induced pluripotent stem cell (iPSC)-derived mesoangioblasts may provide the solution to this problem. Although, the idea of using iPSC-derived cell therapies has been proposed for quite some time, our understanding of how the immune system interacts with these cells is inadequate. Herein, we show that iPSC-derived mesoangioblasts (HIDEMs) from healthy donors and, importantly, limb-girdle muscular dystrophy 2D patients exert immunosuppressive effects on T cell proliferation. Interferon gamma (IFN-γ) and tumour necrosis factor alpha (TNF-α) play crucial roles in the initial activation of HIDEMs and importantly indoleamine 2,3 dioxygenase (IDO) and prostaglandin E2 (PGE-2) were identified as key mechanisms involved in HIDEM suppression of T cell proliferation. Together with recent studies confirming the myogenic function and regenerative potential of these cells, we suggest that HIDEMs could provide an unlimited alternative source for mesoangioblast-based therapies.

The use of 3-dimensional tissue cultures is gaining popularity in many fields including drug discovery, toxicity testing and tissue engineering. Currently most of the techniques used to prepare these 3D tissues are time consuming and cannot be reproduced easily. There is an urgent need to optimize the preparation of these 3D tissue cultures. This study evaluated the use of synthetic hydrogel polymers used to manufacture soft contact lenses to guide cells to form multicellular tissue-like structures. It was found that bovine chondrocytes and porcine dental pulp stem cells were able to form 3D tissue structures when placed inside a soft contact lens. Commercially available microarrays, 96 or 384 well plates manufactured using synthetic hydrogel polymers may help overcome many reproducibility issues and simplify the 3D tissue culture process.

Burn injury results in the acute loss of bone as well as the development of progressive vitamin D deficiency. Bone loss occurs acutely due to resorption, which is then followed by apoptosis of osteoblasts preventing repair of the bone loss. The acute resorption is due to a combination of the inflammatory response and the stress response to the burn injury. The resultant production of inflammatory cytokines and endogenous glucocorticoids initially stimulate the osteoblasts to produce RANK ligand, which stimulates marrow stem cell differentiation into osteoclasts. As the stress response persists for approximately one year post-burn the glucocorticoids produced by the body will cause osteoblast apoptosis and adynamic bone, impairing the ability of bone to recover its resorptive losses. The vitamin D deficiency is due to the failure to supplement the diet of burn patients with vitamin D on discharge from hospital and to failure of the skin to make normal quantities of vitamin D on sunlight exposure. Because the bone resorption can be prevented by the acute administration of bisphosphonates it is unlikely that vitamin D deficiency is responsible for the early-onset bone loss following burns. However, because a deficit in trabecular bone remains for at least two years post-burn, it is possible that vitamin D deficiency prevents the recovery of trabecular bone density over the long term.

Background: Arthroscopic shoulder surgery is increasingly performed as a day case procedure. Optimal post-operative pain relief remains a challenge due to considerable variations in the level of pain experienced between individuals. Our aim was to examine whether the preoperative electrical pain threshold was a strong predictor of elevated postoperative pain levels following arthroscopic subacromial decompression (ASD) surgery. Methods: Forty consenting patients with American Society of Anesthesiologists (ASA) grade 1-2 presenting for elective ASD surgery were recruited. Patients’ electrical pain thresholds were measured preoperatively using a PainMatcher® (Cefar Medical AB, Lund, Sweden) device. Following surgery under general anaesthesia, the maximum pain experienced at rest and movement was recorded using a visual analogue scale until the end of postoperative day four. Results: In univariate analyses (t-test), the postoperative pain experienced (Area Under Curve) was significantly greater in patients with a low pain threshold as compared with a high pain threshold at both rest (mean 12.5, S.E. 1.7 v mean 6.5, S.E.1.2. P=0.008) and on movement (mean 18.7, S.E. 1.5 v mean 14.1, S.E.1.4. P=0.031). In multivariate analyses, adjusting for additional extra analgesia, the pain experienced postoperatively was significantly greater in the low pain threshold group both at rest (mean difference 4.9, 95% CI 1.5 to 8.4, P=0.007) and on movement (mean difference 4.1, 95%CI 0.03 to 8.2, P=0.049). Conclusions: Preoperative pain threshold can predict postoperative pain level following ASD of the shoulder. Trial registration: Clinicaltrials.gov identifier: NCT01351363 Level of Evidence: II

Human mesoangioblasts are currently in a phase I/II clinical trial for the treatment of patients with Duchenne muscular dystrophy. However, limitations associated with the finite life span of these cells combined with the significant numbers of mesoangioblasts required to treat all of the skeletal muscles in these patients restricts their therapeutic potential. Induced pluripotent stem cell (iPSC)-derived mesoangioblasts may provide the solution to this problem. Although, the idea of using iPSC-derived cell therapies has been proposed for quite some time, our understanding of how the immune system interacts with these cells is inadequate. Herein, we show that iPSC-derived mesoangioblasts (HIDEMs) from healthy donors and, importantly, limb-girdle muscular dystrophy 2D patients exert immunosuppressive effects on T cell proliferation. Interferon gamma (IFN-γ) and tumour necrosis factor alpha (TNF-α) play crucial roles in the initial activation of HIDEMs and importantly indoleamine 2,3 dioxygenase (IDO) and prostaglandin E2 (PGE-2) were identified as key mechanisms involved in HIDEM suppression of T cell proliferation. Together with recent studies confirming the myogenic function and regenerative potential of these cells, we suggest that HIDEMs could provide an unlimited alternative source for mesoangioblast-based therapies.

Burn injury results in the acute loss of bone as well as the development of progressive vitamin D deficiency. Bone loss occurs acutely due to resorption, which is then followed by apoptosis of osteoblasts preventing repair of the bone loss. The acute resorption is due to a combination of the inflammatory response and the stress response to the burn injury. The resultant production of inflammatory cytokines and endogenous glucocorticoids initially stimulate the osteoblasts to produce RANK ligand, which stimulates marrow stem cell differentiation into osteoclasts. As the stress response persists for approximately one year post-burn the glucocorticoids produced by the body will cause osteoblast apoptosis and adynamic bone, impairing the ability of bone to recover its resorptive losses. The vitamin D deficiency is due to the failure to supplement the diet of burn patients with vitamin D on discharge from hospital and to failure of the skin to make normal quantities of vitamin D on sunlight exposure. Because the bone resorption can be prevented by the acute administration of bisphosphonates it is unlikely that vitamin D deficiency is responsible for the early-onset bone loss following burns. However, because a deficit in trabecular bone remains for at least two years post-burn, it is possible that vitamin D deficiency prevents the recovery of trabecular bone density over the long term.