Development of acetabular retroversion in LCPD hips-an observational radiographic study from early stage to healing.

BACKGROUND: Acetabular retroversion is observed frequently in healed Legg-Calvé-Perthes disease (LCPD). Currently, it is unknown at which stage and with what prevalence retroversion occurs because in non-ossified hips, retroversion cannot be measured with standard radiographic parameters. METHODS: In a retrospective, observational study; we examined pelvic radiographs in children with LCPD the time point of occurrence of acetabular retroversion and calculated predictive factors for retroversion. Between 2004 and 2017, we included 55 children with a mean age of 5.7 ± 2.4 years at diagnosis. The mean radiographic follow-up was 7.0 ± 4.4 years. We used two new radiographic parameters which allow assessment of acetabular version in non-ossified hips: the pelvic width index and the ilioischial angle. They are based on the fact that the pelvic morphology differs depending on the acetabular version. These parameters were compared among the four Waldenström stages and to the contralateral side. Logistic regression analysis was performed to determine predictive factors for acetabular retroversion. RESULTS: Both parameters differed significantly among the stages of Waldenström (p < 0.003 und 0.038, respectively). A more retroverted acetabulum was found in stage II and III (prevalence ranging from 54 to 56%) compared to stage I and IV (prevalence ranging from 23 to 39%). In hips of the contralateral side without LCPD, the prevalence of acetabular retroversion was 0% in all stages for both parameters. Predictive factors for retroversion were younger age at stage II and IV, collapse of the lateral pillar in stage II or a non-dysplastic hip. CONCLUSIONS: This is the first study evaluating acetabular version in children with LCPD from early stage to healing. In the developing hip, LCPD may result in acetabular retroversion and is most prevalent in the fragmentation (stage II) and early healing stage (stage III). Partial correction of acetabular retroversion can occur after healing. This has a potential clinical impact on the timing and type of surgical correction, especially in pelvic osteotomies for correction of acetabular version. LEVEL OF EVIDENCE: Level III, retrospective observational study.

Improved osseointegration using porcine xenograft compared to demineralized bone matrix for the treatment of critical defects in a small animal model.

BACKGROUND: Autograft (AG) is the gold standard bone graft due to biocompatibility, osteoconductivity, osteogenicity, and osteoinductivity. Alternatives include allografts and xenografts (XG). METHODS: We investigated the osseointegration and biocompatibility of a decellularized porcine XG within a critical defect animal model. We hypothesized that the XG will result in superior osseointegration compared to demineralized bone matrix (DBM) and equivalent immune response to AG. Critical defects were created in rat femurs and treated with XG, XG plus bone morphogenetic protein (BMP)-2, DBM, or AG. Interleukin (IL)-2 and IFN-gamma levels (inflammatory markers) were measured from animal blood draws at 1 week and 1 month post-operatively. At 1 month, samples underwent micro-positron-emission tomography (microPET) scans following 18-NaF injection. At 16 weeks, femurs were retrieved and sent for micro-computerized tomography (microCT) scans for blinded grading of osseointegration or were processed for histologic analysis with tartrate resistant acid phosphatase (TRAP) and pentachrome. RESULTS: Enzyme linked immunosorbent assay testing demonstrated greater IL-2 levels in the XG vs. AG 1 week post-op; which normalized by 28 days post-op. MicroPET scans showed increased uptake within the AG compared to all groups. XG and XG + BMP-2 showed a trend toward increased uptake compared with DBM. MicroCT scans demonstrated increased osseointegration in XG and XG + BMP groups compared to DBM. Pentachrome staining demonstrated angiogenesis and endochondral bone formation. Furthermore, positive TRAP staining in samples from all groups indicated bone remodeling. CONCLUSIONS: These data suggest that decellularized and oxidized porcine XG is biocompatible and at least equivalent to DBM in the treatment of a critical defect in a rat femur model.

Bone xenotransplantation: A review of the history, orthopedic clinical literature, and a single-center case series.

BACKGROUND: One-half of all orthopedic surgeries require bone grafting for successful outcomes in fusions, reconstructive procedures, and the treatment of osseous defects resulting from trauma, tumor, infection, or congenital deformity. Autologous bone grafts are taken from the patient's own body and remain the "gold standard" graft choice but are limited in supply and impart significant patient morbidity. Xenograft bone is an attractive alternative from donors with controlled biology, in large supply and at a theoretically lower cost. Clinical results with xenograft bone for orthopedic applications have been mixed in the limited clinical trials published. METHODS: In the current review, we introduce fundamental principles of bone grafting, systematically review all orthopedic clinical studies reporting outcomes on patients transplanted with xenograft bone, and we present our own clinical results from patients grafted with bovine bone in foot and ankle reconstructive procedures. RESULTS: Thirty-one clinical studies were identified for review and the majority (47%) were from spine surgery literature. Favorable results were reported in 44% of studies while 47% of studies reported poor outcomes and discouraged use of xenograft bone products. In our own clinical series, xenograft failed to integrate with host bone in 58% of cases and persistent pain was reported in 83% of cases. CONCLUSIONS: This is the first systematic review of clinical results reported after bone xenotransplantation for orthopaedic surgery applications. Current literature does not support the use of xenograft bone products and our institution's results are consistent with this conclusion. Our laboratory has reported promising pre-clinical results with a xenograft product derived from porcine cancellous bone, but additional testing is required before considering clinical translation.

Investigating the Osteoinductive Potential of a Decellularized Xenograft Bone Substitute.

Bone grafting is the second most common tissue transplantation procedure worldwide. One of the alternative methods for bone repair under investigation is a tissue-engineered bone substitute. An ideal property of tissue-engineered bone substitutes is osteoinductivity, defined as the ability to stimulate primitive cells to differentiate into a bone-forming lineage. In the current study, we use a decellularization and oxidation protocol to produce a porcine bone scaffold and examine whether it possesses osteoinductive potential and can be used to create a tissue-engineered bone microenvironment. The decellularization protocol was patented by our lab and consists of chemical decellularization and oxidation steps using combinations of deionized water, trypsin, antimicrobials, peracetic acid, and triton-X100. To test if the bone scaffold was a viable host, preosteoblasts were seeded and analyzed for markers of osteogenic differentiation. The osteoinductive potential was observed in vitro with similar osteogenic markers being expressed in preosteoblasts seeded on the scaffolds and demineralized bone matrix. To assess these properties in vivo, scaffolds with and without preosteoblasts preseeded were subcutaneously implanted in mice for 4 weeks. MicroCT scanning revealed 1.6-fold increased bone volume to total volume ratio and 1.4-fold increase in trabecular thickness in scaffolds after implantation. The histological analysis demonstrates new bone formation and blood vessel formation with pentachrome staining demonstrating osteogenesis and angiogenesis, respectively, within the scaffold. Furthermore, CD31+ staining confirmed the endothelial lining of the blood vessels. These results demonstrate that porcine bone maintains its osteoinductive properties after the application of a patented decellularization and oxidation protocol developed in our laboratory. Future work must be performed to definitively prove osteogenesis of human mesenchymal stem cells, biocompatibility in large animal models, and osteoinduction/osseointegration in a relevant clinical model in vivo. The ability to create a functional bone microenvironment using decellularized xenografts will impact regenerative medicine, orthopedic reconstruction, and could be used in the research of multiple diseases.

A porcine xenograft-derived bone scaffold is a biocompatible bone graft substitute: An assessment of cytocompatibility and the alpha-Gal epitope.

BACKGROUND: Xenografts are an attractive alternative to traditional bone grafts because of the large supply from donors with predictable morphology and biology as well as minimal risk of human disease transmission. Clinical series involving xenograft bone transplantation, most commonly from bovine sources, have reported poor results with frequent graft rejection and failure to integrate with host tissue. Failures have been attributed to residual alpha-Gal epitope in the xenograft which humans produce natural antibody against. To the authors' knowledge, there is currently no xenograft-derived bone graft substitute that has been adopted by orthopedic surgeons for routine clinical use. METHODS: In the current study, a bone scaffold intended to serve as a bone graft substitute was derived from porcine cancellous bone using a tissue decellularization and chemical oxidation protocol. In vitro cytocompatibility, pathogen clearance, and alpha-Gal quantification tests were used to assess the safety of the bone scaffold intended for human use. RESULTS: In vitro studies showed the scaffold was free of processing chemicals and biocompatible with mouse and human cell lines. When bacterial and viral pathogens were purposefully added to porcine donor tissue, processing successfully removed these pathogens to comply with sterility assurance levels established by allograft tissue providers. Critically, 98.5% of the alpha-Gal epitope was removed from donor tissue after decellularization as shown by ELISA inhibition assay and immunohistochemical staining. CONCLUSIONS: The current investigation supports the biologic safety of bone scaffolds derived from porcine donors using a decellularization protocol that meets current sterility assurance standards. The majority of the highly immunogenic xenograft carbohydrate was removed from donor tissue, and these findings support further in vivo investigation of xenograft-derived bone tissue for orthopedic clinical application.

Pulseless Supracondylar Humerus Fracture With Anterior Interosseous Nerve or Median Nerve Injury-An Absolute Indication for Open Reduction?

BACKGROUND: Optimal management for a pulseless supracondylar humerus fracture associated with anterior interosseous nerve (AIN) or median nerve injury is unclear. The purpose of this study was to determine the incidence of pulseless supracondylar humerus fractures associated with AIN or median nerve injury, to assess open versus closed surgical management, to determine factors associated with the need for neurovascular intervention, and to report the outcome. METHODS: A retrospective review was performed at 4 pediatric trauma hospitals on all patients who sustained a Gartland III or IV supracondylar humerus fracture with the combination of absent distal palpable pulses and AIN or median nerve injury between 2000 and 2014. Choice of treatment, details regarding preoperative and postoperative exam findings, follow-up course, and outcome were recorded. RESULTS: A total of 71 patients met inclusion criteria; 52 patients (73%) underwent closed reduction (CR); 19 patients (27%) underwent open reduction (OR) and early antecubital fossa exploration. The index procedure of CR plus percutaneous pinning was sufficient treatment in 50 (of 52, 96%) patients with only 2 requiring reoperation. One patient developed compartment syndrome approximately 9 hours after CRPP (13.5 h after time of injury) and underwent emergent fasciotomies. Of the 19 patients who underwent OR and early exploration, 6 needed vascular procedures, 5 required detethering of entrapped surrounding fibrous tissues. Forty patients were diagnosed with median nerve palsy versus 31 diagnosed with AIN palsy. There was no significant difference between patients presenting with median nerve versus AIN palsy, with similar rates of need for OR (10/40; 25% vs. 9/31; 29%), rate of compartment syndrome (3/40; 7.5% vs. 3/31; 9.7%), need for reoperation (4/40; 10% vs. 6.5%), and ultimate resolution of nerve palsy (4/36; 20.1% vs. 3/30; 10%). Compartment syndrome developed in 6 (of 71, 8.5%) patients and was associated with poor perfusion status on presentation and delayed time from injury to surgery. In patients with at least 3-month neurological follow-up, 59 (of 61, 97%) patients had complete resolution of nerve palsy. CONCLUSIONS: Although previous authors have suggested a pulseless SCH fx with an associated AIN or median nerve injury should be treated with exploration and OR, 70% (50/71) of the patients in this series were treated with a CR. In this series, both AIN and median nerve palsies among patients presenting with pulseless extremity and Gartland III or IV SCH fracture, offer similar rates of OR, risk of compartment syndrome, and resolution of nerve palsy. LEVEL OF EVIDENCE: Level IV.

The Development of a Xenograft-Derived Scaffold for Tendon and Ligament Reconstruction Using a Decellularization and Oxidation Protocol.

PURPOSE: To evaluate the biological, immunological, and biomechanical properties of a scaffold derived by architectural modification of a fresh-frozen porcine patella tendon using a decellularization protocol that combines physical, chemical, and enzymatic modalities. METHODS: Porcine patellar tendons were processed using a decellularization and oxidation protocol that combines physical, chemical, and enzymatic modalities. Scaffolds (n = 88) were compared with native tendons (n = 70) using histologic, structural (scanning electron microscopy, porosimetry, and tensile testing), biochemical (mass spectrometry, peracetic acid reduction, DNA quantification, alpha-galactosidase [α-gal] content), as well as in vitro immunologic (cytocompatibility, cytokine induction) and in vivo immunologic nonhuman primate analyses. RESULTS: A decrease in cellularity based on histology and a significant decrease in DNA content were observed in the scaffolds compared with the native tendon (P < .001). Porosity and pore size were increased significantly (P < .001). Scaffolds were cytocompatible in vitro. There was no difference between native tendons and scaffolds when comparing ultimate tensile load, stiffness, and elastic modulus. The α-gal xenoantigen level was significantly lower in the decellularized scaffold group compared with fresh-frozen, nondecellularized tissue (P < .001). The in vivo immunological response to implanted scaffolds measured by tumor necrosis factor-α and interleukin-6 levels was significantly (P < .001) reduced compared with untreated controls in vitro. These results were confirmed by an attenuated response to scaffolds in vivo after implantation in a nonhuman primate model. CONCLUSIONS: Porcine tendon was processed via a method of decellularization and oxidation to produce a scaffold that possessed significantly less inflammatory potential than a native tendon, was biocompatible in vitro, of increased porosity, and with significantly reduced amounts of α-gal epitope while retaining tensile properties. CLINICAL RELEVANCE: Porcine-derived scaffolds may provide a readily available source of material for musculoskeletal reconstruction and repair while eliminating concerns regarding disease transmission and the morbidity of autologous harvest.

Intraoperative Evaluation of Acetabular Morphology in Hip Arthroscopy Comparing Standard Radiography Versus Fluoroscopy: A Cadaver Study.

PURPOSE: To compare quantitative measurements of acetabular morphology obtained using intraoperative fluoroscopy, to standardized anteroposterior (AP) pelvis radiographs. METHODS: Ten dried human pelvis specimens (20 hips) were imaged using hip-centered fluoroscopy and standardized AP pelvis radiographs. Each hip was evaluated for acetabular version and coverage, including lateral center edge (LCE) angle, acetabular index (AI), total anterior and posterior coverage, and crossover sign. RESULTS: No statistically significant differences existed between the mean LCE angle (fluoroscopy 36.5° ± 8.3° v plain films 36.1° ± 7.9°, P = .59), acetabular index (0.6° ± 8.6° v 0.2° ± 7.1°, P = .61), ACM angle (44.0° ± 2.6° v 44.1° ± 3.8°, P = .89), Sharp's angle (31.8° ± 5.7° v 32.4° ± 3.9°, P = .44), and the total femoral coverage (80.9% ± 6.4% v 80.7% ± 7.5%, P = .83). Conversely, total anterior coverage (30.7% ± 8.5% v 33.3% ± 8.2%, P < .0001) appeared significantly decreased and the total posterior coverage (54.1% ± 6.9% v 49.1% ± 7.8%, P < .0001) appeared significantly increased in fluoroscopy compared with plain film radiographs. Fluoroscopy also failed to identify the presence of a crossover sign in 30% and underestimated the retroversion index (9% ± 16%, v 13% ± 16%, P = .016). CONCLUSIONS: The values for the LCE angle and AI determined by hip-centered fluoroscopy did not differ from those obtained by standardized AP plain film radiography. However, fluoroscopy leads to a more anteverted projection of the acetabulum with significantly decreased total anterior coverage, significantly increased total posterior coverage, and underestimated signs of retroversion compared with standardized AP pelvis radiography. CLINICAL RELEVANCE: This study shows reliable LCE and AI angles but significant differences in the projected anteversion of the acetabulum between standardized AP pelvis radiography and hip-centered fluoroscopy.

Maintenance of acetabular correction following PAO: a multicenter study comparing stainless-steel and titanium screws.

Stainless-steel screws are commonly used for fragment fixation during periacetabular osteotomy (PAO) at our institutions. Titanium is reserved for patients with documented nickel allergies. Titanium screws possess a significantly lower Young's modulus than stainless steel and, therefore, potentially less resistance to physiologic loading. Thus, we hypothesized that the use of titanium screws might be associated with changes in acetabular correction prior to healing. The aim of this study was to compare the maintenance of acetabular correction following PAO using stainless-steel or titanium screws. A documented nickel allergy was confirmed with an allergy specialist. Patients' age at surgery, gender and BMI were collected. The lateral center-edge angle of Wiberg (LCEA), medial center-edge angle (MCEA), anterior wall index (AWI), posterior wall index (PWI) and Tönnis angle were measured. The delta value for radiographic parameters was calculated as the difference between values immediately post-operation and at 6 months post-operation. Only age at surgery (P < 0.001) and the pre-operative LCEA (P = 0.013) were significantly different between groups (Tables I and II). The remaining pre- and post-operative radiological measurements were similar (Table II). Comparison of delta values at 6 months follow-up indicated no significant differences between screw types (Table III). No patients in the titanium group had a trans-iliac retrograde screw included in their construct (P = 0.003). All patients healed from their osteotomies. The use of titanium screws in patients with an allergy to nickel was not associated with differences in acetabular correction or the rate of osseous union rates despite its lower inherent mechanical properties.

The science of rotator cuff tears: translating animal models to clinical recommendations using simulation analysis.

PURPOSE: The purpose of this article is to review basic science studies using various animal models for rotator cuff research and to describe structural, biomechanical, and functional changes to muscle following rotator cuff tears. The use of computational simulations to translate the findings from animal models to human scale is further detailed. METHODS: A comprehensive review was performed of the basic science literature describing the use of animal models and simulation analysis to examine muscle function following rotator cuff injury and repair in the ageing population. RESULTS: The findings from various studies of rotator cuff pathology emphasize the importance of preventing permanent muscular changes with detrimental results. In vivo muscle function, electromyography, and passive muscle-tendon unit properties were studied before and after supraspinatus tenotomy in a rodent rotator cuff injury model (acute vs chronic). Then, a series of simulation experiments were conducted using a validated computational human musculoskeletal shoulder model to assess both passive and active tension of rotator cuff repairs based on surgical positioning. CONCLUSION: Outcomes of rotator cuff repair may be improved by earlier surgical intervention, with lower surgical repair tensions and fewer electromyographic neuromuscular changes. An integrated approach of animal experiments, computer simulation analyses, and clinical studies may allow us to gain a fundamental understanding of the underlying pathology and interpret the results for clinical translation.

Effect of cyclic strain on tensile properties of a naturally derived, decellularized tendon scaffold seeded with allogeneic tenocytes and associated messenger RNA expression.

Naturally derived tendon scaffolds have the potential to improve the treatment of flexor tendon injuries. Seeded and unseeded tendon scaffolds were maintained in the presence or absence of physiologic strain for 7 days. After 7 days, the tensile properties and associated messenger RNA expression were compared. Seeded scaffolds maintained in the absence of strain had significantly lower tensile properties than unseeded tendons and fresh-frozen tendons. The loss of tensile properties was associated with elevated matrix metalloproteinase-2 and collagen III expression. Tensile properties of seeded scaffolds maintained in the presence of strain for 7 days after seeding did not differ from those of fresh-frozen tendons. This study demonstrates that the tensile properties of seeded, naturally derived tendon scaffolds will degrade rapidly in the absence of cyclic strain. Seeded scaffolds used for tendon reconstruction should be maintained under cyclic strain to maintain essential tensile properties.

Advances in additive manufacturing of polycaprolactone based scaffolds for bone regeneration.

Critical sized bone defects are difficult to manage and currently available clinical/surgical strategies for treatment are not completely successful. Polycaprolactone (PCL) which is a biodegradable and biocompatible thermoplastic can be 3D printed using medical images into patient specific bone implants. The excellent mechanical properties and low immunogenicity of PCL makes it an ideal biomaterial candidate for 3D printing of bone implants. Though PCL suffers from the limitation of being bio-inert. Here we describe the use of PCL as a biomaterial for 3D printing for bone regeneration, and advances made in the field. The specific focus is on the different 3D printing techniques used for this purpose and various modification that can enhance bone regeneration following the development pathways. We further describe the effect of various scaffold characteristics on bone regeneration both in vitro and the translational assessment of these 3D printed PCL scaffolds in animal studies. The generated knowledge will help understand cell-material interactions of 3D printed PCL scaffolds, to further improve scaffold chemistry and design that can replicate bone developmental processes and can be translated clinically.

Direct 3D printing of decellularized matrix embedded composite polycaprolactone scaffolds for cartilage regeneration.

Treatment options for large osteochondral injuries (OCIs) are limited by donor tissue scarcity, morbidity, and anatomic mismatch. 3D printing technology can produce patient-specific scaffolds to address these large defects. Thermoplastics like polycaprolactone (PCL) offer necessary mechanical properties, but lack bioactivity. We fabricated 3D printed PCL scaffolds embedded with polylactic acid microspheres containing decellularized cartilage matrix (DM). DM incorporation within polylactic acid microspheres prevented its thermal degradation during the 3D printing process. The scaffolds replicated the mechanical properties of native cartilage and demonstrated controlled release of DM proteins. Human mesenchymal stem cells (hMSCs) seeded on the composite scaffolds with DM and cultured in basal media self-assembled into aggregates mimicking mesenchymal condensates during embryonic development. The DM composite scaffolds also induced higher expression of biochemical markers of cartilage development than controls, providing evidence for their translational application in the treatment of OCIs. The present study demonstrates the potential of direct incorporation of DM with thermoplastics for 3D printing of patient-specific scaffolds for osteochondral regeneration.

Pediatric and Adolescent Fractures of the Acetabulum Treated With ORIF: What Are Their Functional Outcomes?

OBJECTIVES: To evaluate the functional outcomes of pediatric and adolescent patients (<18 year old) who sustained acetabulum fractures that were treated with open reduction internal fixation (ORIF). DESIGN: Retrospective cohort. SETTING: Level 1 trauma center. PATIENTS: Thirty-four pediatric and adolescent patients underwent acetabulum fracture ORIF between 2001 and 2018. Of the operatively treated patients, 21 patients had sufficient follow-up (>6 months), one died after fixation secondary to other traumatic injuries, and 12 patients were lost to follow-up. INTERVENTION: Acetabulum fracture ORIF. MAIN OUTCOME MEASUREMENT: The SF-36 Health Survey and Short Musculoskeletal Functional Assessment (SMFA) were compared with population norms. The modified Merle d'Aubigné clinical hip score, Matta radiologic outcome, and postoperative complications were also documented. RESULTS: Functional outcome data were available at a mean of 5 years 2 months. Mean SF-36 scores were 44.8 and 50.1 for the physical component score and mental component scores, respectively, which did not differ significantly from US population norms (physical component score mean: 50, P = 0.061 and mental component score mean: 50, P = 0.973). Furthermore, the mean SMFA Bother Index score was 18.6, which is not significantly different from the population norm mean of 13.8 (P = 0.268). However, the function index mean was 31.9, which was significantly worse than the population norm mean of 12.7 (P = 0.001). Two patients with a delayed reduction (>6 hours) of an acetabulum fracture dislocation had poor outcomes related to the development of avascular necrosis and post-traumatic osteoarthritis. CONCLUSION: In this small cohort, 86% (18/21) of these patients had a favorable functional outcome with the exception of the SMFA Functional Index that was significantly less than population norms. Although long-term follow-up is needed, we advocate for operative management of pediatric and adolescent acetabulum fractures when adult displacement and instability criteria are present. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Alginate based hydrogel inks for 3D bioprinting of engineered orthopedic tissues.

3D printed hydrogels have emerged as a novel tissue engineering and regeneration platform due to their ability to provide a suitable environment for cell growth. To obtain a well-defined scaffold with good post-printing shape fidelity, a proper hydrogel ink formulation plays a crucial role. In this regard, alginate has received booming interest owing to its biocompatibility, biodegradability, easy functionalization, and fast gelling behavior. Hence, this review highlights the significance of alginate-based hydrogel inks for fabricating 3D printed scaffolds for bone and cartilage regeneration. Herein, we discuss the fundamentals of direct extrusion 3D bioprinting method and provide a comprehensive overview of various alginate-based hydrogel ink formulations that have been used so far. We also summarize the requirements of hydrogel inks and 3D printed scaffolds to achieve similarity to the native tissue environment. Finally, we discuss the challenges, and research directions relevant for future clinical translation.

Tissue Engineering Strategies for Treating Avascular Necrosis of the Femoral Head.

Avascular necrosis (AVN) of the femoral head commonly leads to symptomatic osteoarthritis of the hip. In older patients, hip replacement is a viable option that restores the hip biomechanics and improves pain but in pediatric, adolescent, and young adult patients hip replacements impose significant activity limitations and the need for multiple revision surgeries with increasing risk of complication. Early detection of AVN requires a high level of suspicion as diagnostic techniques such as X-rays are not sensitive in the early stages of the disease. There are multiple etiologies that can lead to this disease. In the pediatric and adolescent population, trauma is a commonly recognized cause of AVN. The understanding of the pathophysiology of the disease is limited, adding to the challenge of devising a clinically effective treatment strategy. Surgical techniques to prevent progression of the disease and avoid total hip replacement include core decompression, vascular grafts, and use of bone-marrow derived stem cells with or without adjuncts, such as bisphosphonates and bone morphogenetic protein (BMP), all of which are partially effective only in the very early stages of the disease. Further, these strategies often only improve pain and range of motion in the short-term in some patients and do not predictably prevent progression of the disease. Tissue engineering strategies with the combined use of biomaterials, stem cells and growth factors offer a potential strategy to avoid metallic implants and surgery. Structural, bioactive biomaterial platforms could help in stabilizing the femoral head while inducing osteogenic differentiation to regenerate bone and provide angiogenic cues to concomitantly recover vasculature in the femoral head. Moreover, injectable systems that can be delivered using a minimal invasive procedure and provide mechanical support the collapsing femoral head could potentially alleviate the need for surgical interventions in the future. The present review describes the limitations of existing surgical methods and the recent advances in tissue engineering that are leading in the direction of a clinically effective, translational solution for AVN in future.

The corona mortis: is it a rare and dangerous anomaly in adolescents undergoing periacteabular osteotomy?

The corona mortis (CM) is a vascular connection between the obturator and external iliac or internal epigastric vessels that has historically been identified as a source of hemorrhage in pelvic surgery. However, its frequency, location, proximity to the osteotomies performed, vascular contributions and impact on blood loss in patients undergoing periacetabular osteotomy (PAO) are unknown. We sought to identify the frequency, origin, location relative to osteotomies performed during surgery and impact on blood loss of the CM. Preoperative magnetic resonance imaging (MRI) of the hips of 28 adolescent patients (56 hips) undergoing PAO was retrospectively reviewed for the presence of a CM. When identifiable, the size, nature (arterial or venous), orientation, position relative to the iliopectineal eminence (IPE) and associated estimated blood loss (EBL) were recorded. 75% (21/28) of patients possessed an identifiable, ipsilateral CM to the site of PAO, 90% of which were venous and 10% arterial. The vessel was typically 8.3 ± 3.8 mm medial and 11.1 ± 5.3 mm caudal from the anterosuperomedial edge of the IPE. There was no significant difference in the amount of EBL (519 ± 260 versus 694 ± 369 ml) or need for post-op transfusions (1/21 versus 0/7) between patients who possessed a CM and those who did not, respectively (P = 0.21). CM was more prevalent in this study than previously reported. However, the presence of an ipsilateral CM was not associated with an increase in EBL or transfusion during routine PAO surgery using modern surgical techniques.

Obesity as a Predictor of Outcomes in Type III and Type IV Supracondylar Humerus Fractures.

OBJECTIVES: To investigate the association of obesity with fracture characteristics and outcomes of operatively treated pediatric supracondylar humerus fractures. DESIGN: Retrospective multicenter. SETTING: Two Level I pediatric hospitals. PATIENTS: Patients (age <18 years) with operatively treated Gartland type III and type IV fractures 2010-2014. INTERVENTION: Closed or open reduction and percutaneous pinning of supracondylar humerus fractures. MAIN OUTCOME MEASURE: Incidence of Gartland IV fracture, preoperative nerve palsy, open reduction and complication rates. RESULTS: Patients in the obese group had a significantly higher likelihood of having a Gartland IV fracture (not obese: 17%; obese: 35%; P = 0.007). There was a significantly higher incidence of nerve palsy on presentation in the obese group (not obese: 20%; obese: 33%; P = 0.03). No significant differences were found between groups regarding incidence of open reduction, compartment syndrome, and rates of reoperation. CONCLUSIONS: The present study demonstrates that obese children with a completely displaced supracondylar humerus fractures have an increased risk of Gartland type IV and preoperative nerve palsy compared with normal weight children. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Fibrinogen activates focal adhesion kinase (FAK) promoting colorectal adenocarcinoma growth.

BACKGROUND: We previously showed that fibrinogen is a major determinant of the growth of a murine model of colorectal cancer (CRC). OBJECTIVE: Our aim was to define the mechanisms coupling fibrin(ogen) to CRC growth. RESULTS: CRC tumors transplanted into the dorsal subcutis of Fib- mice were less proliferative and demonstrated increased senescence relative to those grown in Fib+ mice. RNA-seq analyses of Fib+ and Fib- tumors revealed 213 differentially regulated genes. One gene highly upregulated in tumors from Fib- mice was stratifin, encoding 14-3-3σ, a master regulator of proliferation/senescence. In a separate cohort, we observed significantly increased protein levels of 14-3-3σ and its upstream and downstream targets (i.e., p53 and p21) in tumors from Fib- mice. In vitro analyses demonstrated increased tumor cell proliferation in a fibrin printed three-dimensional environment compared with controls, suggesting that fibrin(ogen) in the tumor microenvironment promotes tumor growth in this context via a tumor cell intrinsic mechanism. In vivo analyses showed diminished activation of focal adhesion kinase (FAK), a key negative regulator of p53, in Fib- tumors. Furthermore, nuclear magnetic resonance-based metabolomics demonstrated significantly reduced metabolic activity in tumors from Fib- relative to Fib+ mice. Together, these findings suggest that fibrin(ogen)-mediated engagement of colon cancer cells activates FAK, which inhibits p53 and its downstream targets including 14-3-3σ and p21, thereby promoting cellular proliferation and preventing senescence. CONCLUSIONS: These studies suggest that fibrin(ogen) is an important component of the colon cancer microenvironment and may be exploited as a potential therapeutic target.

An acellular, allograft-derived meniscus scaffold in an ovine model.

PURPOSE: The purpose of this study was to develop a meniscus scaffold that has increased porosity and maintains the native meniscus extracellular matrix in an ovine model. METHODS: The medial menisci of skeletally mature ovine (n = 16) were harvested; half were made into meniscus scaffolds (n = 8), and half remained intact (n = 8). Intact and scaffold meniscus tissues were compared by use of histology, DNA content analysis, in vitro cellular biocompatibility assays, and ultrastructural analysis. An additional 16 knees were used to investigate the biomechanics of the intact meniscus compared with the meniscus scaffold. RESULTS: DNA content and histology showed a significant decrease in cellular and nuclear content in the meniscus scaffold (P < .003). Biocompatibility was supported through in vitro cellular assays. Scanning electron microscopy and micro-computed tomography showed a substantial increase in porosity and pore connectivity in the meniscus scaffold compared with the intact meniscus (P < .01). There was no statistical difference between the ultimate load or elastic modulus of the intact and meniscus scaffolds. CONCLUSIONS: In this study a meniscus scaffold was evaluated for potential clinical application as a meniscus transplant construct in an ovine model. The data showed that a decellularized meniscus scaffold with increased porosity was comparable to the intact meniscus, with an absence of in vitro cellular toxicity. Although some compositional alterations of the extracellular matrix are to be expected during processing, it is evident that many of the essential structural components remained functional with maintenance of biomechanical properties. CLINICAL RELEVANCE: This meniscus scaffold has potential for future clinical application as a meniscus transplant construct.