Semi-transparent organic photovoltaics.

As an economical solar energy conversion technology, organic photovoltaics (OPVs) are regarded as a promising solution to environmental problems and energy challenges. With the highest efficiency of OPVs exceeding 20%, the research focus will shift from efficiency-oriented aspects to commercialization-oriented aspects in the near future. Semi-transparent OPVs (STOPVs) are one of the most possible commercialized forms of OPVs, and have achieved power conversion efficiency over 14% with average visible light transmittance over 20% so far. In this tutorial review, we first systematically summarize the device structures, operating principles and evaluation parameters of STOPVs, and compare them with those of opaque OPVs. Then, strategies to construct high-performance STOPVs by cooperatively optimizing materials and devices are proposed. Methods to realize the scale-up of STOPVs in terms of minimization of electrode and interconnect resistance are summarized. The potential applications of STOPVs in multifunctional windows, agrivoltaics and floating photovoltaics are also discussed. Finally, this review highlights major challenges and research directions that need to be addressed prior to the future commercialization of STOPVs.

Quantitative muscle ultrasound in children with Duchenne muscular dystrophy: Comparing to magnetic resonance imaging.

OBJECTIVE: There is a need today for favorable biomarkers to follow up on the disease progression and therapeutic response in patients with Duchenne muscular dystrophy (DMD). This study evaluates whether quantitative muscle ultrasound (QMUS) or magnetic resonance imaging (MRI) is more suitable for the assessment of DMD in China. METHODS: Thirty-six boys with DMD, who were treated with prednisone from baseline to month 12, were enrolled in this longitudinal, observational cohort study. Muscle thickness and echo intensity on QMUS and T1-weighted MRI grading were measured in the right rectus femoris. RESULTS: Scores for muscle thickness and echo intensity in QMUS and T1-weighted MRI grading showed significant correlations with the clinical characteristics of muscle strength, timed testing, and quality of life (p < 0.05). Scores for muscle thickness and echo intensity on QMUS also showed good correlations with T1-weighted MRI grading (p < 0.05). However, 15 of 36 boys with DMD did not undergo MRI examinations for various reasons. CONCLUSIONS: QMUS and MRI can be used as biomarkers for tracking DMD to some extent. Both have strengths and weaknesses and the specific needs and goals of the clinical or research project are what make one preferable to the other.

Retrospective analysis of traumatic triradiate cartilage injury in children.

BACKGROUND: To summarize and analyze the epidemiological characteristics, treatment and corresponding curative effect of triradiate cartilage injury(TCI) in children after trauma, to provide a theoretical basis for early diagnosis and improvement of treatment. METHODS: The TCI was classified according to Bucholz classification, and the final curative effect was evaluated with Harris Hip Score and imaging examination during follow-up. Finally, a comprehensive analysis was made by reviewing the cases in the literature combined with the patients in our hospital. RESULTS: A total of 15 cases (18 hips) of triradiate cartilage injuries were collected in our hospital. There was 1 hip with type I injury, nine hips with type II injury, two hips with type IV injury, one hip with type V injury and five hips with type VI injury. Among the 12 cases with complete follow-up, the bone bridge was found in or around the triradiate cartilage in 8 cases, early fusion of triradiate cartilage occurred in 5 patients, 3 cases had hip dysplasia, 4 cases had a subluxation of the femoral head, and HHS was excellent in 8 cases and good in 4 cases. CONCLUSION: The early diagnosis of TCI is still a difficult problem. Conservative treatment is often the first choice. The overall prognosis of acetabular fractures involving triradiate cartilage is poor. The formation of the bone bridge in triradiate cartilage usually indicates the possibility of premature closure, which may lead to severe complications of post-traumatic acetabular dysplasia and subluxation of the femoral head.

Acetabular roof lesions in children: a descriptive study and literature review.

BACKGROUND: Acetabular roof lesions (ARLs) in children are uncommon and may involve a variety of diseases. The acetabular roof is the main weight-bearing area of the hip joint, and lesions affecting the acetabular roof lead to fluid accumulation in the hip joint, causing hip pain and claudication. Methods for diagnosing and treating ARLs and the prognosis after treatment are rarely reported. We present our experience in a group of children and teenagers with ARLs to retrospectively explore the clinical and imaging features and histopathological diagnosis and report the treatment methods and follow-up observations. METHODS: Patients with ARLs admitted to the Children's Hospital of Chongqing Medical University from April 2011 to September 2018 were selected retrospectively. We collected the basic information of patients (name, sex, age), main symptoms and signs, results of various laboratory tests, treatment methods, and intraoperative observations through the hospital medical record system. We collected X-ray, computed tomography (CT), magnetic resonance imaging (MRI) and pathological examination data through the Picture Archiving and Communications System. Follow-up data were collected through an outpatient medical record system, telephone, and chat software (such as WeChat). We used descriptive methods to analyze the lesion structure and destruction mode based on the imaging findings and histopathological diagnosis. RESULTS: There were 14 ARL patients, including 6 with eosinophilic granuloma (EG), 5 with chronic osteomyelitis, 2 with bone cyst, and 1 with tuberculosis. One patient underwent percutaneous needle biopsy, 2 underwent open biopsy, and 11 underwent curettage; among them, 5 patients also underwent bone grafting. These lesions had no characteristic imaging findings, and the diagnosis was mainly based on histopathological examination. Most patients showed complete symptom resolution and good hip function at the 1-year follow-up. CONCLUSION: ARLs are not common in children. The types of lesions are diverse and mostly benign, with EG being most common. Malignant tumors may also occur, such as Ewing's sarcoma, non-Hodgkin's lymphoma, metastases and neuroblastoma. CT and MRI can be helpful in diagnosing certain cases, but incisional biopsy is required in most cases.

In Situ Complex with by-product HCl and Release Chloride Ions to Dissolve Aramid.

Because of the strong hydrogen-bond interaction among macromolecular chains, the addition of chloride salts is generally needed to offer Cl- ions for the dissolution of aromatic polyamides. In this paper, poly-(benzimidazole-terephthalamide) which complexed with by-product HCl during polymerization (PABI-HCl) was prepared and imidazole compound as cosolvent was added into dimethylacetamide (DMAc) to dissolve PABI-HCl. Due to stronger affinity to protons, imidazole compound could in-situ complex with HCl of PABI-HCl and form imidazolium hydrochloride. Then imidazolium hydrochloride would ionize and produce much free Cl- ions which acted as stronger hydrogen-bond acceptor to disrupt interaction among macromolecular chains. As a result, solubility of PABI-HCl in DMAc was improved significantly in existence of small amount of imidazole compound. Moreover, DMAc-imidazole mixture was utlized for synthesis of different kinds of aramids and no precipitation was observed with progress of the reaction. So the mixture was suitable to be utlized as solvent for polymerization of aramid.

Internal Fixation With Absorbable Rods for the Treatment of Displaced Radial Neck Fractures in Children.

BACKGROUND: The treatment of radial neck fractures with complete displacement or severe displacement and an angle of >30 degrees is controversial. The currently used methods, including the Metaizeau technique, are associated with drawbacks such as imperfect reduction, epiphyseal damage, and delayed functional recovery. To overcome these drawbacks, we used absorbable rod fixation followed by early functional training for the treatment of displaced radial neck fractures in children. METHODS: In this study, 68 patients (age, 4 to 12 y; average, 8.4 y; average angle, 58 degrees; average displacement, 53%) with radial neck fractures with Salter-Harris grades II to IV underwent lateral elbow open reduction and absorbable rod fixation. At 3 weeks postoperatively, the patients' plaster casts were removed, and functional training was started. RESULTS: Anatomic reduction was achieved in all patients. We followed-up 68 patients for 6 months to 4 years (average, 41 mo). No cases of radial nerve injury, radial bone necrosis, myositis ossificans, and postoperative infection were observed. The functional recovery was "excellent" in 43 patients, "good" in 13 patients, "average" in 12 patients, and "bad" in 0 patients, according to the Morrey evaluation standard. CONCLUSION: Open reduction with absorbable rod fixation for the treatment of displaced radial neck fractures in children was feasible and was a choice in children. LEVEL OF EVIDENCE: Therapeutic II.

Daily prednisone treatment in Duchenne muscular dystrophy in southwest China.

INTRODUCTION: In this study we aimed to determine the influence of daily prednisone treatment in Duchenne muscular dystrophy (DMD) by performing a prospective, randomized, placebo-controlled trial in southwestern China. METHODS: Sixty-six children with DMD (4-12 years of age) were divided randomly into prednisone and placebo groups. Efficacy and safety of daily prednisone at 0.75 mg/kg/day were evaluated over 12 months by muscle strength and function, quality of life (QoL), quantitative muscle ultrasound (QMUS), and side effects. RESULTS: Significant improvements in muscle strength and function, QoL, and QMUS were observed in the prednisone group compared with the placebo-treated group (P < 0.05). Changes in body weight, height, body mass index, and diastolic blood pressure were similar in both groups (P > 0.05). CONCLUSIONS: This pilot study in southwestern China found that daily prednisone at 0.75 mg/kg/day is suitable for children with DMD. It slowed disease progression and improved QoL and QMUS. Moderate side effects were generally well tolerated.

Visualization of the wrist ganglion capsule by methylene blue staining as an aid for complete resection in children.

PURPOSE: To evaluate the effectiveness of methylene blue staining during ganglion resection in children, to assess ganglion resection and minimize recurrence. METHODS: From August 2007 to March 2011, 36 children with dorsal or volar wrist ganglions with an average size of 2 cm (range, 1-4 cm), including 5 recurrent cases, underwent resection performed with intraoperative methylene blue marking of the cyst wall. RESULTS: We found recurrence in one patient after 2 years; no obvious complications were observed in any patient. CONCLUSIONS: Methylene blue staining of the ganglion during resection may be helpful for achieving complete resection. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic II.

Polymer Fiber Rigid Network with High Glass Transition Temperature Reinforces Stability of Organic Photovoltaics.

Organic photovoltaics (OPVs) need to overcome limitations such as insufficient thermal stability to be commercialized. The reported approaches to improve stability either rely on the development of new materials or on tailoring the donor/acceptor morphology, however, exhibiting limited applicability. Therefore, it is timely to develop an easy method to enhance thermal stability without having to develop new donor/acceptor materials or donor-acceptor compatibilizers, or by introducing another third component. Herein, a unique approach is presented, based on constructing a polymer fiber rigid network with a high glass transition temperature (Tg) to impede the movement of acceptor and donor molecules, to immobilize the active layer morphology, and thereby to improve thermal stability. A high-Tg one-dimensional aramid nanofiber (ANF) is utilized for network construction. Inverted OPVs with ANF network yield superior thermal stability compared to the ANF-free counterpart. The ANF network-incorporated active layer demonstrates significantly more stable morphology than the ANF-free counterpart, thereby leaving fundamental processes such as charge separation, transport, and collection, determining the device efficiency, largely unaltered. This strategy is also successfully applied to other photovoltaic systems. The strategy of incorporating a polymer fiber rigid network with high Tg offers a distinct perspective addressing the challenge of thermal instability with simplicity and universality.

Cross-talk between EGF and BMP9 signalling pathways regulates the osteogenic differentiation of mesenchymal stem cells.

Mesenchymal stem cells (MSCs) are multipotent progenitors, which give rise to several lineages, including bone, cartilage and fat. Epidermal growth factor (EGF) stimulates cell growth, proliferation and differentiation. EGF acts by binding with high affinity to epidermal growth factor receptor (EGFR) on the cell surface and stimulating the intrinsic protein tyrosine kinase activity of its receptor, which initiates a signal transduction cascade causing a variety of biochemical changes within the cell and regulating cell proliferation and differentiation. We have identified BMP9 as one of the most osteogenic BMPs in MSCs. In this study, we investigate if EGF signalling cross-talks with BMP9 and regulates BMP9-induced osteogenic differentiation. We find that EGF potentiates BMP9-induced early and late osteogenic markers of MSCs in vitro, which can be effectively blunted by EGFR inhibitors Gefitinib and Erlotinib or receptor tyrosine kinase inhibitors AG-1478 and AG-494 in a dose- and time-dependent manner. Furthermore, EGF significantly augments BMP9-induced bone formation in the cultured mouse foetal limb explants. In vivo stem cell implantation experiment reveals that exogenous expression of EGF in MSCs can effectively potentiate BMP9-induced ectopic bone formation, yielding larger and more mature bone masses. Interestingly, we find that, while EGF can induce BMP9 expression in MSCs, EGFR expression is directly up-regulated by BMP9 through Smad1/5/8 signalling pathway. Thus, the cross-talk between EGF and BMP9 signalling pathways in MSCs may underline their important roles in regulating osteogenic differentiation. Harnessing the synergy between BMP9 and EGF should be beneficial for enhancing osteogenesis in regenerative medicine.

Toward high-performance organic photovoltaics: the new cooperation of sequential solution-processing and promising non-fullerene acceptors.

Organic photovoltaics (OPVs) have long been a hot topic due to their light weight, low cost, and flexibility. Simple blend-based OPVs have sufficient donor/acceptor (D/A) interfaces and high exciton dissociation efficiency, which result in certified high power conversion efficiency (PCE) exceeding 18%. However, the difficult morphology control and poor device stability limit further progress toward higher PCE and future application. Sequential solution-processing with tunable vertical phase distribution, D/A interfaces, and charge transportation pathways not only benefit device stability but can also overcome the up-scaling challenge. In recent years, the development of non-fullerene acceptors (NFAs) has been very rapid, which is attributed to their tunable energy levels, bandgaps, planarity, and crystallinity. In this minireview, the opportunities for the cooperation of sequential solution-processing and NFAs are revealed based on their characteristics, such as diverse molecular shapes, abundant functional groups and heteroatoms, and various aggregation states for NFAs; independent active layer processing, controllable D/A interfaces, and excellent device stability for sequential solution-processing. Few but important existing examples are discussed to display the prospects of sequential solution-processed fullerene-free OPVs toward high PCE, good device stability, high semitransparency, and large-area industrial manufacture. Finally, some possible research directions are predicted and the main issues that need to be overcome are proposed for sequential solution-processed fullerene-free OPVs toward higher performance.

Flexible pressure sensors with high pressure sensitivity and low detection limit using a unique honeycomb-designed polyimide/reduced graphene oxide composite aerogel.

It is still a challenge to fabricate flexible pressure sensors that possess high sensitivity, ultralow detection limit, wide sensing range, and fast response for intelligent electronic devices. We here demonstrate superelastic and highly pressure-sensitive polyimide (PI)/reduced graphene oxide (rGO) aerogel sensors with unique honeycomb structure, which were designed and fabricated using a bidirectional freezing technique. This unique honeycomb structure with large aspect ratio is composed of aligned thin lamellar layers and interconnected bridges. The combination of the aligned lamellar layers and the bridges endows the aerogel sensors with high pressure sensitivity (1.33 kPa-1), ultralow detection limit (3 Pa), broad detection range (80% strain, 59 kPa), fast response time (60 ms), and excellent stability during cycling (over 1000 cycles). Remarkably, the aerogel sensors maintain stable piezoresistive performance at -50 °C, 100 °C, and 200 °C in air, indicating promising potential applications in harsh environments. Owing to the high sensitivity and wide sensing range, the aerogel sensors have been used to detect a full-range of human motion including small-scale motion monitoring (wrist pulse, blowing, puffing) and large-scale movement monitoring (finger bending, elbow bending, walking, running). These advantages make the composite aerogels attractive for high-performance flexible pressure sensors and wearable electronic devices.

Retrospective study of open reduction and internal fixation of lateral humeral condyle fractures with absorbable screws and absorbable sutures in children.

BACKGROUND: Lateral humeral condyle fractures are the second most common elbow fracture in children. Displaced and rotated fractures require stabilization and reduction. Kirschner wires (K-wires) are most commonly used in the fixation of these fractures. Here, we introduce a new fixation method that uses an absorbable screw. We aim to determine if it is feasible to treat lateral humeral condyle fractures with an absorbable screw by comparing functional outcomes following absorbable screw fixation vs. K-wire fixation. METHODS: Between May 2007 and September 2010, 86 patients were treated with absorbable screws (43 patients) or K-wire (43 patients). All patients had been diagnosed with lateral condyle fractures that were classified as either Jacob type II (unstable) or III. One absorbable screw (3.5 mm-diameter) was used for fixation in 1 group, while two 1.6 to 1.8 mm K-wires were used in the other group. Patients were followed 6 months about the elbow function according to Broberg and Morrey standard. On 5-7 years, the patients were followed about the carrying angle (valgus deformities and varus deformities), range of motion (flexion loss and extension loss), prominent lateral condyle, symptomatic implants, and fishtail deformity. RESULTS: Anatomic reduction was achieved in all patients. Each group had one radial nerve injury that were present preoperatively. Nerve function recovered spontaneously within 3 to 4 weeks of surgery in both patients. No patient developed necrosis of the capitulum in both groups. Nine patients in K-wires group and 2 in absorbable screw group developed symptomatic implants (P = .048). On the sixth month, there was no significant difference on elbow function according to Broberg and Morrey standard. On 5 to 7 years (average, 6.7 ±â€Š1.3 years), valgus deformities was 6.8 ±â€Š1.2 vs 5.7 ±â€Š0.8, varus deformities was 7.2 ±â€Š1.5 vs 5.1 ±â€Š1.9, flexion loss was 12.4 ±â€Š2.2 vs 9.5 ±â€Š3.1, extension loss was 11.1 ±â€Š3.1 vs 10.2 ±â€Š2.7, prominent lateral condyle was 27.9% vs 37.2%, fishtail deformity was 7.3% vs 4.9%, no significant difference between these groups. CONCLUSIONS: Open reduction with absorbable screw fixation is feasible and safe for the treatment of lateral condyle fractures of the humerus in children. LEVEL OF EVIDENCE: Therapeutic III.

Towards enhanced tribological performance as water-based lubricant additive: Selective fluorination of graphene oxide at mild temperature.

HYPOTHESIS: It is still difficult to prepare hydrophilic fluorinated graphene with abundant oxygen functional groups and high F/C ratio. EXPERIMENTS: Herein, selective fluorination for graphene oxide (GO) was realized to prepare highly oxygen/fluorine dual functionalized graphene (OFG) under a mild temperature without damaging the sheet structure. Its O/C and F/C ratios came up to 0.58 and 0.19 respectively, which contained the intactly reserved oxygen functional groups from GO during fluorination and C-F bonds from addition reaction between aromatic region and F2, as demonstrated via X-ray photoelectron spectroscopy (XPS), thermo gravimetric analysis (TGA), Raman measurements and so on. FINDINGS: Experiments and density functional theory (DFT) calculations revealed that oxygen functional groups in-situ promoted addition reaction between aromatic region and F2, and the critical point was confirmed that oxygen functional groups began to react with F2 by substitution reaction. As-prepared OFG presented a 47% and 31% decrease of wear rate compared with that of pure water and GO, respectively. During friction process, the abundant oxygen functional groups of OFG contributed to hydrophilic property and introduced fluorine played an important role in enhancing the tribological performance by self-lubricating behavior. Such mild and simple method is achieved to expand the application of fluorinated graphene in aqueous environment.

Idiopathic Intervertebral Disc Calcification in a Child: An Atypical Case Involving Many Segments.

CASE: A seven-year-old girl presented to the emergency department with severe neck pain and restricted movement of sudden onset. A basic neurological examination supplemented by radiography showed calcification within the intervertebral disc at the C6-C7 level. Computed tomography and magnetic resonance imaging of the spine confirmed the diagnosis and revealed additional calcification within the spine at the C3-C4, C7-T1, T1-T2, T4-T5, and T5-T6 levels. CONCLUSION: Idiopathic intervertebral disc calcification is a rare condition in children, and its etiology remains unclear. In this report, we present a rare case of idiopathic intervertebral disc calcification at numerous levels in a seven-year-old girl. The clinical and radiographic findings, laboratory examination, and follow-up are discussed.

[Soft tissue reconstruction for secondary deformity after correction of Wassel type IV-D thumb duplication].

OBJECTIVE: To investigate an effective therapeutic method for the secondary deformity after the correction of the Wassel type IV thumb duplication. METHODS: 9 cases of Wassel W-D Complex thumb deformities in children with postoperative secondary deformity, including 6 males and 3 female, were treated. The age ranged from 2.0 to 14 years old with an average of 5.3 years old. During the operation, the anatomical structure was dissected to observe the structure and alignment of the flexor tendon as well as anatomical structure of the joint. In the meantime, the flexor pollicis longus tendon was shifted, A2 pulley was reconstructed, joint capsule was released and contracted, the end point of thenar was shifted. Kirschner wires fixation were used for about 4-5 weeks, the brace fixation for about 3 months. RESULTS: All the patients had radial side skin contracture of the interphalangeal joint, radial deviation of the thumb tip, radial side contracture and ulnar relaxation of the joint capsule. Flexor hallucis longus tendon was located in front of the radial side of the proximal phalanx, with no wrapped sheath or A2 pulley. Flexor hallucis longus tendon was attached to the thumb tip substrate, of which 1/3 was located in the center and 2/3 in the radial side. The thumb tip rotated about 10 degrees-15 degrees to the radial side. The patients were followed up for 6-38 months, with an average of 24 months. We adopted Tada standard to evaluate the follow-up results as excellent in 7 cases, good in 1 case, poor in 1 case. CONCLUSIONS: Soft tissue reconstruction for the secondary deformity after the correction of the Wassel type IV-D thumb duplication is an effective method. Application of the brace after removal of Kirschner wires has an important role in preventing the secondary deformity.

The Current and Future Therapies for Human Osteosarcoma.

Osteosarcoma (OS) is the most common non-hematologic malignant tumor of bone in adults and children. As sarcomas are more common in adolescents and young adults than most other forms of cancer, there are a significant number of years of life lost secondary to these malignancies. OS is associated with a poor prognosis secondary to a high grade at presentation, resistance to chemotherapy and a propensity to metastasize to the lungs. Current OS management involves both chemotherapy and surgery. The incorporation of cytotoxic chemotherapy into therapeutic regimens escalated cure rates from <20% to current levels of 65-75%. Furthermore, limb-salvage surgery is now offered to the majority of OS patients. Despite advances in chemotherapy and surgical techniques over the past three decades, there has been stagnation in patient survival outcome improvement, especially in patients with metastatic OS. Thus, there is a critical need to identify novel and directed therapy for OS. Several Phase I trials for sarcoma therapies currently ongoing or recently completed have shown objective responses in OS. Novel drug delivery mechanisms are currently under phase II and III clinical trials. Furthermore, there is an abundance of preclinical research which holds great promise in the development of future OS-directed therapeutics. Our continuously improving knowledge of the molecular and cell-signaling pathways involved in OS will translate into more effective therapies for OS and ultimately improved patient survival. The present review will provide an overview of current therapies, ongoing clinical trials and therapeutic targets under investigation for OS.

BMP9 signaling in stem cell differentiation and osteogenesis.

Bone morphogenetic proteins (BMPs) are members of the TGF-ß superfamily and play a critical role in skeletal development, bone formation and stem cell differentiation. Disruptions in BMP signaling result in a variety of skeletal and extraskeletal anomalies. BMP9 is a poorly characterized member of the BMP family and is among the most osteogenic BMPs, promoting osteoblastic differentiation of mesenchymal stem cells (MSCs) both in vitro and in vivo. Recent findings from various in vivo and molecular studies strongly suggest that the mechanisms governing BMP9-mediated osteoinduction differ from other osteogenic BMPs. Many signaling pathways with diverse functions have been found to play a role in BMP9-mediated osteogenesis. Several of these pathways are also critical in the differentiation of other cell lineages, including adipocytes and chondrocytes. While BMP9 is known to be a potent osteogenic factor, it also influences several other pathways including cancer development, angiogenesis and myogenesis. Although BMP9 has been demonstrated as one of the most osteogenic BMPs, relatively little is known about the specific mechanisms responsible for these effects. BMP9 has demonstrated efficacy in promoting spinal fusion and bony non-union repair in animal models, demonstrating great translational promise. This review aims to summarize our current knowledge of BMP9-mediated osteogenesis by presenting recently completed work which may help us to further elucidate these pathways.

Noggin resistance contributes to the potent osteogenic capability of BMP9 in mesenchymal stem cells.

Mesenchymal stem cells (MSCs) are multipotent progenitors and can differentiate into osteogenic, chondrogenic, and adipogenic lineages. Bone morphogenetic proteins (BMPs) play important roles in stem cell proliferation and differentiation. We recently demonstrated that BMP9 is a potent but less understood osteogenic factor. We previously found that BMP9-induced ectopic bone formation is not inhibited by BMP3. Here, we investigate the effect of BMP antagonist noggin on BMP9-induced osteogenic differentiation. BMP antagonists noggin, chording, gremlin, follistatin, and BMP3 are highly expressed in MSCs, while noggin and follistatin are lowly expressed in more differentiated pre-osteoblast C2C12 cells. BMP9-induced osteogenic markers and matrix mineralization are not inhibited by noggin, while noggin blunts BMP2, BMP4, BMP6, and BMP7-induced osteogenic markers and mineralization. Likewise, ectopic bone formation by MSCs transduced with BMP9, but not the other four BMPs, is resistant to noggin inhibition. BMP9-induced nuclear translocation of Smad1/5/8 is not affected by noggin, while noggin blocks BMP2-induced activation of Smad1/5/8 in MSCs. Noggin fails to inhibit BMP9-induced expression of downstream targets in MSCs. Thus, our results strongly suggest that BMP9 may effectively overcome noggin inhibition, which should at least in part contribute to BMP9's potent osteogenic capability in MSCs.

Mesenchymal Progenitor Cells and Their Orthopedic Applications: Forging a Path towards Clinical Trials.

Mesenchymal progenitor cells (MPCs) are nonhematopoietic multipotent cells capable of differentiating into mesenchymal and nonmesenchymal lineages. While they can be isolated from various tissues, MPCs isolated from the bone marrow are best characterized. These cells represent a subset of bone marrow stromal cells (BMSCs) which, in addition to their differentiation potential, are critical in supporting proliferation and differentiation of hematopoietic cells. They are of clinical interest because they can be easily isolated from bone marrow aspirates and expanded in vitro with minimal donor site morbidity. The BMSCs are also capable of altering disease pathophysiology by secreting modulating factors in a paracrine manner. Thus, engineering such cells to maximize therapeutic potential has been the focus of cell/gene therapy to date. Here, we discuss the path towards the development of clinical trials utilizing BMSCs for orthopaedic applications. Specifically, we will review the use of BMSCs in repairing critical-sized defects, fracture nonunions, cartilage and tendon injuries, as well as in metabolic bone diseases and osteonecrosis. A review of www.ClinicalTrials.gov of the United States National Institute of Health was performed, and ongoing clinical trials will be discussed in addition to the sentinel preclinical studies that paved the way for human investigations.