Minimally invasive fasciotomy using a lighted retractor in the treatment of chronic exertional compartment syndrome.

Chronic exertional compartment syndrome can be a debilitating cause of lower leg pain that typically affects young, healthy people during a variety of aerobic activities. Conservative management has produced a poor success rate and numerous techniques for surgical decompression have been described. Many of these, however, involve blind fascial dissection which increases the risk of direct nerve injury or insufficient fascial release. We describe a novel technique of mini-open fasciotomy using a lighted retractor which enables direct visualization of the fascia and the superficial peroneal nerve using a single, small incision. By the use of a 3- to 4-cm laterally based incision, a lighted retractor with fiber-optic illumination is introduced into the subcutaneous plane and advanced distally and proximally. The retractor gently elevates the subcutaneous tissues while focusing light directly into the surgical area and a long Metzenbaum scissors is then used to release the fascia under direct vision. Fasciotomy using this technique avoids the risks of blind fascial release and is a straightforward, safe, and effective method for compartment decompression.

Outcome of total hip and knee arthroplasty in HIV-infected patients: A systematic review.

Significant advances in the treatment of Human Immunodeficiency Virus (HIV) have occurred in recent times, with life expectancy now approaching the normal population. Therefore, patients with HIV will increasingly be undergoing joint replacement in the future, however concerns remain regarding the complications and outcome in this patient cohort. The aim was to assess the outcome of total hip and knee arthroplasty in HIV-infected patients. A systematic search of the literature using MOOSE reporting guidelines was performed to assess the outcome of hip and knee arthroplasty in HIV-infected patients. The primary outcome was infection. Secondary outcome was all-cause revision. The search yielded 552 results, of which 19 met the inclusion criteria, comprising 5.819.412 joint replacements. The overall quality of the studies was poor with significant heterogeneity between the studies. Infection and revision appeared to be more likely to occur in HIV positive patients compared to HIV negative patients. A subgroup analysis of four studies revealed a risk ratio of 3.31 and 2.25 for increase in infection and revision respectively in HIV positive patients. This systematic review and meta-analysis demonstrates an increased risk of infection and revision in HIV infected patients undergoing total hip and knee arthroplasty. However, these findings are based on poor quality evidence in a limited number of studies and need to be interpreted with caution. Further research should concentrate on large, well-designed, prospective studies, that control for co-morbidities and employ standardised outcome measures to allow for direct comparison.

Molecular Mechanism of Ischaemic Preconditioning of Skeletal Muscle In Vitro.

Introduction Ischaemic preconditioning (IPC) is a phenomenon whereby tissues develop an increased tolerance to ischaemia and subsequent reperfusion if first subjected to sublethal periods of ischaemia. Despite extensive investigation of IPC, the molecular mechanism remains largely unknown. Our aim was to show genetic changes that occur in skeletal muscle cells in response to IPC. Methods We established an in vitro model of IPC using a human skeletal muscle cell line. Gene expression of both control and preconditioned cells at various time points was determined. The genes examined were hypoxia-inducible factor-1 alpha (HIF-1 alpha), early growth response 1 (EGR1), JUN, and FOS. HIF-1 alpha is a marker of hypoxia. EGR1, JUN, and FOS are early response genes and may play a role in the protective responses induced by IPC. Results HIF-1 alpha was upregulated following one and two hours of simulated ischaemia (p = 0.076 and 0.841, respectively) verifying that hypoxic conditions were met using our model. Expression of EGR1 and FOS was upregulated and peaked after one hour of hypoxia (p = 0.001 and <0.00, respectively). cFOS was upregulated at two and three hours of hypoxia. IPC prior to simulated hypoxia resulted in a greater level of upregulation of EGR1, JUN and FOS genes (p = <0.00, 0.047, and <0.00 respectively). Conclusion This study has supported the use of our hypoxic model for studying IPC in vitro. IPC results in a greater upregulation of protective genes in skeletal muscle cells exposed to hypoxia than in control cells. We have demonstrated hitherto unknown molecular mechanisms of IPC in cell culture.

Biofabrication of soft tissue templates for engineering the bone-ligament interface.

Regenerating damaged tissue interfaces remains a significant clinical challenge, requiring recapitulation of the structure, composition, and function of the native enthesis. In the ligament-to-bone interface, this region transitions from ligament to fibrocartilage, to calcified cartilage and then to bone. This gradation in tissue types facilitates the transfer of load between soft and hard structures while minimizing stress concentrations at the interface. Previous attempts to engineer the ligament-bone interface have utilized various scaffold materials with an array of various cell types and/or biological cues. The primary goal of this study was to engineer a multiphased construct mimicking the ligament-bone interface by driving differentiation of a single population of mesenchymal stem cells (MSCs), seeded within blended fibrin-alginate hydrogels, down an endochondral, fibrocartilaginous, or ligamentous pathway through spatial presentation of growth factors along the length of the construct within a custom-developed, dual-chamber culture system. MSCs within these engineered constructs demonstrated spatially distinct regions of differentiation, adopting either a cartilaginous or ligamentous phenotype depending on their local environment. Furthermore, there was also evidence of spatially defined progression toward an endochondral phenotype when chondrogenically primed MSCs within this construct were additionally exposed to hypertrophic cues. The study demonstrates the feasibility of engineering spatially complex soft tissues within a single MSC laden hydrogel through the defined presentation of biochemical cues. This novel approach represents a new strategy for engineering the ligament-bone interface. Biotechnol. Bioeng. 2017;114: 2400-2411. © 2017 Wiley Periodicals, Inc.

Stem cells display a donor dependent response to escalating levels of growth factor release from extracellular matrix-derived scaffolds.

Numerous growth factor delivery systems have been developed for tissue engineering. However, little is known about how the dose of a specific protein will influence tissue regeneration, or how different patients will respond to altered levels of growth factor presentation. The objective of the present study was to assess stem cell chondrogenesis within extracellular-matrix (ECM)-derived scaffolds loaded with escalating levels of transforming growth factor (TGF)-ß3. It was also sought to determine if stem cells display a donor-dependent response to different doses of TGF-ß3, from low (5 ng) to high (200 ng), released from such scaffolds. It was found that ECM-derived scaffolds possess the capacity to bind and release increasing amounts of TGF-ß3, with between 60% and 75% of this growth factor released into the media over the first 12 days of culture. After seeding these scaffolds with human infrapatellar fat pad-derived stem cells (FPSCs), it was found that cartilage-specific ECM accumulation was greatest for the higher levels of growth factor loading. Importantly, soak-loading cartilage ECM-derived scaffolds with high levels of TGF-ß3 always resulted in at least comparable levels of chondrogenesis to controls where this growth factor was continuously added to the culture media. Similar results were observed for FPSCs from all donors, although the absolute level of secreted matrix did vary from donor to donor. Therefore, while no single growth factor release profile will be optimal for all patients, the results of this study suggest that the combination of a highly porous cartilage ECM-derived scaffold coupled with appropriate levels of TGF-ß3 can consistently drive chondrogenesis of adult stem cells. Copyright © 2016 John Wiley & Sons, Ltd.

Porous Scaffolds Derived from Devitalized Tissue Engineered Cartilaginous Matrix Support Chondrogenesis of Adult Stem Cells.

ECM-derived scaffolds have previously been developed from devitalized native cartilage and successfully used in tissue engineering. Such ECM-based biomaterials are commonly derived from animal tissue, which may not represent the ideal source for applications in human. Native human ECM can be used as an alternative to xenogeneic tissue; however, its supply may be limited, leading to the need for a more readily available source of such biomaterials. The objective of this study was to compare devitalized native and tissue engineered cartilaginous ECM as chondro-permissive scaffolds for tissue engineering. To this end, porous scaffolds were produced using ECM derived from porcine articular cartilage and cartilaginous sheets engineered using human bone marrow stem cells. An identical process was used to produce scaffolds from three different types of devitalized ECMs, namely that derived from porcine cartilage (Native), human engineered cartilaginous sheets (Eng), and human engineered cartilaginous sheets generated in the presence of growth factor releasing microspheres (Eng-MS). Scaffolds produced using both devitalized engineered and native ECM possessed similar mechanical properties, pore size and GAG content, although were compositionally distinct. After being seeded with human infrapatellar fat pad stem cells, the engineered ECM-derived scaffolds (no Microspheres) supported less robust cartilage matrix deposition than native ECM scaffolds. However, more chondro-permissive scaffolds could be generated using cartilaginous ECM engineered in the presence of TGF-ß1 releasing microspheres. Eng-MS scaffolds supported comparable levels of GAG synthesis to native ECM scaffolds. These results demonstrate that engineered ECM can be used to produce scaffolds for cartilage tissue engineering, overcoming stock limitations and other barriers associated with native autogeneic, allogeneic, and xenogeneic tissues. Such engineered ECM holds significant promise as an off-the-shelf chondro-permissive scaffold for articular cartilage repair.

Engineering Tissues That Mimic the Zonal Nature of Articular Cartilage Using Decellularized Cartilage Explants Seeded with Adult Stem Cells.

Articular cartilage (AC) possesses uniquely complex mechanical properties; for example its stiffness increases with depth through the tissue and it softens when compressed. These properties are integral to the function of AC and can be attributed to the tissue's collagen network and how it interacts with negatively charged proteoglycans. In this study, scaffolds containing arrays of channels were produced from decellularized AC explants derived from skeletally immature and mature pigs. These scaffolds were then repopulated with human infrapatellar fat pad derived stem cells (FPSCs). After 4 weeks in culture, FPSCs filled channels within the decellularized explants with a matrix rich in proteoglycans and collagen. Cellular and neo-matrix alignment within these scaffolds appeared to be influenced by the underlying collagen architecture of the decellularized cartilage. Repopulating scaffolds derived from decellularized skeletally mature cartilage with FPSCs led to the development of engineered cartilage with depth-dependent mechanical properties mimicking aspects of native tissue. Furthermore, these constructs displayed the characteristic strain softening behavior of AC. These findings highlight the importance of the collagen network to engineering mechanically functional cartilage grafts.

A Long-term Retrospective Evaluation of Functional and Radiographic Outcomes of Pediatric Hip Surgery in Hurler Syndrome.

BACKGROUND: After successful hematopoietic stem cell transplantation, maintaining function and mobility have become key goals in the management of patients with Hurler syndrome, (mucopolysaccharoidosis type 1H). The aim of this study was to establish the functional and radiologic outcomes after hip surgery in patients with this condition who had reached skeletal maturity. METHODS: We prospectively followed 13 mucopolysaccharoidosis type 1H patients with closed triradiate cartilages who had undergone hip surgery in a single institution (Our Lady's Children's Hospital, Crumlin) in early childhood, after successful hematopoietic stem cell transplantation. Functional assessment was performed using the Harris Hip Score. Acetabular and femoral head morphology were defined using a pelvic radiograph. RESULTS: The average age at follow-up was 18.6 years (range, 13.2 to 23.8 y). The average length of follow-up from surgical intervention was 14.6 years (range, 10.3 to 21.6 y). The average Harris Hip Score at follow-up was 61.0 (range, 19 to 91). At follow-up, 4 patients were either wheelchair bound or required a walking frame to mobilize in the community. At follow-up, all hips were in-joint with an average center edge angle of 37.7 degrees (range, 0 to 63 degrees). All hips displayed characteristic medial flattening of the femoral head. Ten hips (of 26 hips) showed radiologic degenerative changes with loss of joint space <2 mm. CONCLUSIONS: Despite the surgical provision of stable well-covered hips, active intervention did not prevent the development of radiologic deterioration and clinically significant hip arthritis. We recommend that pediatric hip surgery in Hurler syndrome be designed with the possibility of early hip replacement in mind. LEVEL OF EVIDENCE: Level III.

Bilateral total hip replacement in arthrogryposis multiplex congenita.

The authors present a case of bilateral total hip replacements (THRs) in a 56-year-old patient with arthrogryposis multiplex congenita (AMC). The considerations for the perioperative period and the outcome are discussed. Preoperative planning included an anaesthetic review and availability of fiberoptic intubation due to poor mouth opening. Perioperatively, contractures can make positioning and exposure difficult but in this case a standard posterior approach was taken. Particular attention was given to soft tissue balancing given the theoretical risk of dislocation. There were no perioperative complications. Postoperatively there has been improvement in pain and hip scores but the patient has failed to return to work. Objective improvements in range of motion (ROM) have not been made. This experience suggests THR is a safe and effective treatment for osteoarthritic hip pain in patients with AMC but patients should be informed that ROM is unlikely to improve.

Decellularization of porcine articular cartilage explants and their subsequent repopulation with human chondroprogenitor cells.

Engineering tissues with comparable structure, composition and mechanical functionality to native articular cartilage remains a challenge. One possible solution would be to decellularize xenogeneic articular cartilage in such a way that the structure of the tissue is maintained, and to then repopulate this decellularized matrix with human chondroprogenitor cells that will facilitate the reconstitution, maintenance and eventual turnover of the construct following implantation. The overall objective of this study was to develop a protocol to efficiently decellularize porcine articular cartilage grafts and to identify a methodology to subsequently repopulate such explants with human chondroprogenitor cells. To this end, channels were first introduced into cylindrical articular cartilage explants, which were then decellularized with a combination of various chemical reagents including sodium dodecyl sulfate (SDS) and nucleases. The decellularization protocol resulted in a ~90% reduction in porcine DNA content, with little observed effect on the collagen content and the collagen architecture of the tissue, although a near-complete removal of sulfated glycosaminoglycans (sGAG) and a related reduction in tissue compressive properties was observed. The introduction of channels did not have any detrimental effect on the biochemical or the mechanical properties of the decellularized tissue. Next, decellularized cartilage explants with or without channels were seeded with human infrapatellar fat pad derived stem cells (FPSCs) and cultured chondrogenically under either static or rotational conditions for 10 days. Both channeled and non-channeled explants supported the viability, proliferation and chondrogenic differentiation of FPSCs. The addition of channels facilitated cell migration and subsequent deposition of cartilage-specific matrix into more central regions of these explants. The application of rotational culture appeared to promote a less proliferative cellular phenotype and led to an increase in sGAG synthesis within the explants. Rotational culture also appeared to promote higher cell viability and led to a more even distribution of cells within the channels of decellularized explants. To conclude, this study describes an effective protocol for the decellularization of porcine articular cartilage grafts and a novel methodology for the partial recellularization of such explants with human stem cells. Decellularized soft tissue explants that maintain their native collagen architecture may represent promising scaffolds for musculoskeletal tissue engineering applications.

Controlled release of transforming growth factor-ß3 from cartilage-extra-cellular-matrix-derived scaffolds to promote chondrogenesis of human-joint-tissue-derived stem cells.

The objective of this study was to develop a scaffold derived from cartilaginous extracellular matrix (ECM) that could be used as a growth factor delivery system to promote chondrogenesis of stem cells. Dehydrothermal crosslinked scaffolds were fabricated using a slurry of homogenized porcine articular cartilage, which was then seeded with human infrapatellar-fat-pad-derived stem cells (FPSCs). It was found that these ECM-derived scaffolds promoted superior chondrogenesis of FPSCs when the constructs were additionally stimulated with transforming growth factor (TGF)-ß3. Cell-mediated contraction of the scaffold was observed, which could be limited by the additional use of 1-ethyl-3-3dimethyl aminopropyl carbodiimide (EDAC) crosslinking without suppressing cartilage-specific matrix accumulation within the construct. To further validate the utility of the ECM-derived scaffold, we next compared its chondro-permissive properties to a biomimetic collagen-hyaluronic acid (HA) scaffold optimized for cartilage tissue engineering (TE) applications. The cartilage-ECM-derived scaffold supported at least comparable chondrogenesis to the collagen-HA scaffold, underwent less contraction and retained a greater proportion of synthesized sulfated glycosaminoglycans. Having developed a promising scaffold for TE, with superior chondrogenesis observed in the presence of exogenously supplied TGF-ß3, the final phase of the study explored whether this scaffold could be used as a TGF-ß3 delivery system to promote chondrogenesis of FPSCs. It was found that the majority of TGF-ß3 that was loaded onto the scaffold was released in a controlled manner over the first 10days of culture, with comparable long-term chondrogenesis observed in these TGF-ß3-loaded constructs compared to scaffolds where the TGF-ß3 was continuously added to the media. The results of this study support the use of cartilage-ECM-derived scaffolds as a growth factor delivery system for use in articular cartilage regeneration.

Infrapatellar fat pad-derived stem cells maintain their chondrogenic capacity in disease and can be used to engineer cartilaginous grafts of clinically relevant dimensions.

A therapy for regenerating large cartilaginous lesions within the articular surface of osteoarthritic joints remains elusive. While tissue engineering strategies such as matrix-assisted autologous chondrocyte implantation can be used in the repair of focal cartilage defects, extending such approaches to the treatment of osteoarthritis will require a number of scientific and technical challenges to be overcome. These include the identification of an abundant source of chondroprogenitor cells that maintain their chondrogenic capacity in disease, as well as the development of novel approaches to engineer scalable cartilaginous grafts that could be used to resurface large areas of damaged joints. In this study, it is first demonstrated that infrapatellar fat pad-derived stem cells (FPSCs) isolated from osteoarthritic (OA) donors possess a comparable chondrogenic capacity to FPSCs isolated from patients undergoing ligament reconstruction. In a further validation of their functionality, we also demonstrate that FPSCs from OA donors respond to the application of physiological levels of cyclic hydrostatic pressure by increasing aggrecan gene expression and the production of sulfated glycosaminoglycans. We next explored whether cartilaginous grafts could be engineered with diseased human FPSCs using a self-assembly or scaffold-free approach. After examining a range of culture conditions, it was found that continuous supplementation with both transforming growth factor-ß3 (TGF-ß3) and bone morphogenic protein-6 (BMP-6) promoted the development of tissues rich in proteoglycans and type II collagen. The final phase of the study sought to scale-up this approach to engineer cartilaginous grafts of clinically relevant dimensions (≥2 cm in diameter) by assembling FPSCs onto electrospun PLLA fiber membranes. Over 6 weeks in culture, it was possible to generate robust, flexible cartilage-like grafts of scale, opening up the possibility that tissues engineered using FPSCs derived from OA patients could potentially be used to resurface large areas of joint surfaces damaged by trauma or disease.

Atypical stress-avulsion fracture of the Lisfranc joint complex.

Antiphospholipid syndrome and systemic erythematosus have been associated with metatarsal stress fractures. Stress fractures of the Lisfranc joint complex are uncommon injuries but have been reported to occur most frequently in ballet dancers. We present a case of an avulsion fracture of the Lisfranc joint complex that occurred spontaneously. We have reviewed the association between systemic conditions and metatarsal fractures and proposed a series of hypothetical pathological events that may have contributed to this unusual injury.

A mountain among molehills: removing an impinging large femoral neck osteochondroma in a man with hereditary multiple exostoses.

A 31-year-old man with a history of hereditary multiple exostoses (HME) presented with persistent right groin pain and reduced hip range of movement. Examination demonstrated a positive FADIR (flexion, adduction and internal rotation) test suggesting femoroacetabular impingement (FAI). Investigations showed multiple sessile osteochondromata of the right femur with a dominant anterolateral femoral neck osteochondroma causing flexion block. The patient underwent an uncomplicated proximal femoral exostectomy. Six-week postoperative pain, range of movement and daily activity had greatly improved. This case highlights that even in the setting of multiple osteochondromata, excellent impingement relief can be achieved following selective proximal femoral exostectomy.

Management of total femoral bone loss using a hybrid cement spacer surgical technique.

Standard treatment for an infected total hip arthroplasty is 2-stage revision. Bone loss in infected total hip arthroplasty presents specific challenges during the first stage. This is especially the case when there is massive or complete loss of the femoral bone stock. We describe a technique successfully used in the setting of total femoral bone loss using a hybrid cement spacer. We describe 2 cases illustrating the technique and perioperative course. This technique is a potential solution for total femoral bone loss that allows the individual to maintain mobility before definitive surgery.