Radial Defects Research Articles

Prospective clinical analysis of functional and cosmetic results after closure of radial forearm free flap donor defect with porcine collagen membrane (Rapiderm®)

Prospective clinical analysis of functional and cosmetic results after closure of radial forearm free flap donor defect with porcine collagen membrane (Rapiderm®)

Induction of granulation tissue for the secretion of growth factors and the promotion of bone defect repair

BackgroundThe use of the Masquelet technique in the repair of large bone defects has gained increased acceptance in recent years. The core of this technique is the induction of granulation tissue membrane formation and the implantation of an autologous cancellous bone to reconstruct bone defects in the membrane. In this study, we purpose to explore the structure of induced membrane and the content of growth factors as well to compare between the structure and the effects on osteogenesis of induced membranes and the periosteum in animal models.MethodsBilateral radial bone defects were generated in 32 healthy adult rabbits. The defects were implanted with bone cement. The induced membranes and periosteum were removed after 2, 4, 6, and 8 weeks. Thereafter, hematoxylin-eosin staining (HE) and an enzyme-linked immunosorbent assay (ELISA) were performed to detect vascular endothelial growth factor (VEGF), angiotensin II (ANG-II), bone morphogenetic protein 2 (BMP2), fibroblast growth factor 2 (FGF2), and prostaglandin E2 (PGE2). Proteins isolated from total cell lysates were cultured with mesenchymal stem cells to test the cell proliferation and alkaline phosphatase activity using epimysium as a control.ResultsThe induced membrane and periosteum exhibited similar structures and growth factor levels after 4 and 6 weeks. The highest concentration of BMP-2 and VEGF in the induced membranes occurred in week 6, and FGF-2 and ANG-II concentrations peaked in week 4. The thickness and vascular density of induced membranes gradually decreased with time.ConclusionInduced membrane matured between the 4th and the 6th week and secreted growth factors to promote osteogenesis. The matured induced membrane and periosteum had similar structures and abilities to promote the osteogenesis of mesenchymal stem cells. However, the induced membrane was thicker than the periosteum.

The Treatment Efficacy of Bone Tissue Engineering Strategy for Repairing Segmental Bone Defects Under Osteoporotic Conditions.

The potential of increasing bone mass and preventing fractures in osteoporosis using stem cell therapy is currently an area of intense focus. However, there are very little data available regarding the postfracture bony defect healing efficacy under osteoporotic conditions. This study aims to investigate whether critical-sized segmental bone defects in a rabbit model of osteoporosis could be repaired using an allogenic stem cell-based tissue engineering (TE) approach and to investigate the potential influence of osteoporosis on the treatment efficacy. Rabbit fetal bone marrow mesenchymal stem cells (BMSCs) were harvested and expanded in vitro. Decalcified bone matrix (DBM) scaffolds were then seeded with allogenic fetal BMSCs and cultivated in osteogenic media to engineer BMSC/DBM constructs. Critical-sized radial defects were created in ovariectomized (OVX) rabbits and the defects were repaired either by insertion of BMSC/DBM constructs or by DBM scaffolds alone. Also, nonovariectomized age-matched (non-OVX) rabbits were served as control. At 3 months post-treatment under the osteoporotic condition (OVX rabbits), the BMSC/DBM constructs inserted within the defect generated significantly more bone tissue when compared to the DBM scaffold as demonstrated by the X-ray, microcomputed tomography, and histological analyses. In addition, when compared to a normal nonosteoporotic condition (age-matched non-OVX rabbits), the defect treatment efficacy was adversely affected by the osteoporotic condition with significantly less bone regeneration. This study demonstrated the potential of allogenic fetal BMSC-based TE strategy for repairing bone defects in an osteoporotic condition. However, the treatment efficacy could be considerably compromised in the OVX animals. Therefore, a more sophisticated strategy that addresses the complicated pathogenic conditions associated with osteoporosis is needed.

Large Cryptic Derivative Chromosome 8 Detected by SNP Chromosomal Microarray

Large Cryptic Derivative Chromosome 8 Detected by SNP Chromosomal Microarray

Streamlining NGS Workflows Using Cancer Samples by the Application of Tthe DNA Integrity Number (DIN) from the Genomic DNA Screentape Assay

Streamlining NGS Workflows Using Cancer Samples by the Application of Tthe DNA Integrity Number (DIN) from the Genomic DNA Screentape Assay

Improving the osteogenic efficacy of BMP2 with mechano growth factor by regulating the signaling events in BMP pathway.

Local application of bone morphogenetic protein 2 (BMP2) is known to promote large bone defect healing and BMP2-initiated bone regeneration could be enhanced by an additional mechanical stimulation. The C-terminal 24-a.a. peptide of mechano growth factor (MGF24E), a mechanical-sensitive molecule, has been demonstrated to promote bone healing. Here, we propose a hypothesis that MGF24E could also improve the osteogenic efficacy of BMP2 by regulating the signaling events in the BMP pathway. To confirm the hypothesis, the potentials of MGF24E, BMP2 and BMP2/MGF24E combination treatments on the phosphorylation of Smad 1/5/8, the downstream osteogenesis-related gene expression and osteoblasts mineralization, are investigated with or without the blocking of Smad 5 siRNA. Furthermore, 15-mm rabbit radial bone defects were healed with the cytokine treatments and then evaluated by radiographic examination, histological assessment and immunohistochemical analysis. MGF24E could enhance the BMP2-induced Smad signaling pathway by upregulating the p-Smad protein expression and the downstream osteogenic gene expression. An amount of 5 nM BMP2 in a sub-25 nM concentration of MGF24E medium achieved a higher expression for ALP mRNA and a greater calcium mineral content compared with BMP2 alone. Nevertheless, the inhibition of the MGF24E-regulated BMP pathway could block osteogenesis induced by the dual treatment. In vivo, MGF24E treatment upregulated the endogenous BMP2 expression and the addition of MGF24E into the BMP2 treatment remarkably enhanced the bone mineral density (BMD), the radiographic scores and the histological restoration of the regenerated tissue against BMP2 treatment, suggesting a new strategy for BMP2 in bone defect healing.

Imaging features of humerus, radius and ulna rare malformation

Objective To investigate the imaging features of humerus, radius and ulna rare malformation. Methods A retrospective analysis of the clinical data and image of 40 cases of humerus and the radius and ulna rare developmental deformity andadmitted to hospital affiliated to 1958-2014 years in The Affiliated Hospital of Hangzhou Normal University and the Third Hospital of Hebei Medical University. Take the Swanson classification as the basis, the image changes of different types of malformations are classified and summarized. Results 40 cases of humerus, radius and ulna rare malformation in 19 males and 21 females, age 18 days to 51 years, mean age (11.6 ± 11.5) years; a total of 10 kinds of deformities to Swanson classification, radius and ulna: failure of formation of parts 9 cases, for radial defect; failure of differentiation are congenital radioulnar synostosis 6 cases, Madelung's deformity 12 cases, congenital radial head dislocation 4 cases; duplication 2 cases, for double ulna syndrome; overgrowth 2 cases, as long ulna short radial deformity; undergrowth 1 case, for the micromelia. Humerus and ulna bony involvement: failure of differentiation 1 case, for brachial radial synostosis; failure of formation of parts 1 case, for amelia. There is still one kind of deformity can not be accurately classified as patella cubiti 2 cases. Conclusions Humerus, radius and ulna although more types of malformations and the incidence rate is not high, only a comprehensive understanding of different deformity classification and characteristics, combined with the typical imaging findings in order to arrive at a correct diagnosis to avoid misdiagnosis. Key words: Humerus; Radius; Ulna; Malformations

A resorbable antibiotic-eluting polymer composite bone void filler for perioperative infection prevention in a rabbit radial defect model.

Nearly 1.3 million total joint replacement procedures are performed in the United States annually, with numbers projected to rise exponentially in the coming decades. Although finite infection rates for these procedures remain consistently low, device-related infections represent a significant cause of implant failure, requiring secondary or revision procedures. Revision procedures manifest several-fold higher infection recurrence rates. Importantly, many revision surgeries, infected or not, require bone void fillers to support the host bone and provide a sufficient tissue bed for new hardware placement. Antibiotic-eluting bone void fillers (ABVF), providing both osteoconductive and antimicrobial properties, represent one approach for reducing rates of orthopedic device-related infections. Using a solvent-free, molten-cast process, a polymer-controlled antibiotic-eluting calcium carbonate hydroxyapatite (HAP) ceramic composite BVF (ABVF) was fabricated, characterized, and evaluated in vivo using a bacterial challenge in a rabbit radial defect window model. ABVF loaded with tobramycin eliminated the infectious burden in rabbits challenged with a clinically relevant strain of Staphylococcus aureus (inoculum as high as 107 CFU). Histological, microbiological, and radiographic methods were used to detail the effects of ABVF on microbial challenge to host bone after 8 weeks in vivo. In contrast to the HAP/BVF controls, which provided no antibiotic protection and required euthanasia 3 weeks post-operatively, tobramycin-releasing ABVF animals showed no signs of infection (clinical, microbiological, or radiographic) when euthanized at the 8-week study endpoint. ABVF sites did exhibit fibrous encapsulation around the implant at 8 weeks. Local antibiotic release from ABVF to orthopedic sites requiring bone void fillers eliminated the periprosthetic bacterial challenge in this 8-week in vivo study, confirming previous in vitro results.

Three-Dimensional Porous Gelapin-Simvastatin Scaffolds Promoted Bone Defect Healing in Rabbits.

Treatment of large bone defects (LBDs) is technically demanding. Tissue engineering is an option. A bioactive graft may be produced by combining tissue scaffolds and healing promotive factors in order to accelerate bone repair. We investigated the role of Simvastatin (Sim)-embedded porous Gelapin (Gel) scaffold on experimental bone healing. At first, the effectiveness of different concentrations of Gel and Sim powders was investigated in an experimentally induced femoral hole model in rabbits (n = 6) for 30 days. Then bone bioactive grafts were produced by combination of the effective concentrations of Gel, Sim, and Genipin. The bioimplants were subcutaneously tested in a rabbit model (n = 9) to determine their biocompatibility and biodegradability for 10-30 days. Finally, a large radial bone defect model was produced in rabbits (n = 20), and the bioimplants were inserted in the defects. The untreated and autograft-treated bone defects were served as controls. The animals were euthanized after 30 and 60 days of bone injury. The bone samples were evaluated by radiography, three-dimensional CT scan, bone densitometry, histopathology, and nano-indentation. At a concentration of 5 mg/hole, Sim closed the femoral bone holes after 30 days, while in the defect, autograft, and Gel groups, the holes were open. Both the Gel and Gel-Sim scaffolds were biocompatible and biodegradable. Subcutaneously, the Gel-Sim scaffold was replaced with the newly regenerated ectopic bone after 30 days. After implantation of the Gel-Sim scaffold in the radial bone defects, the scaffold was completely replaced with new woven bone after 30 days which was then matured and remodeled into a cortical bone after 60 days. Sixty days after bone injury, the Gel-Sim-treated defects had significantly higher bone volume, matrix mineralization, elastic modulus, and contact hardness when compared to the controls. The Gel-Sim scaffold may be a suitable option in managing LBDs.

RECQ4 selectively recognizes Holliday junctions.

The RECQ4 protein belongs to the RecQ helicase family, which plays crucial roles in genome maintenance. Mutations in the RECQ4 gene are associated with three insidious hereditary disorders: Rothmund-Thomson, Baller-Gerold, and RAPADILINO syndromes. These syndromes are characterized by growth deficiency, radial ray defects, red rashes, and higher predisposition to malignancy, especially osteosarcomas. Within the RecQ family, RECQ4 is the least characterized, and its role in DNA replication and repair remains unknown. We have identified several DNA binding sites within RECQ4. Two are located at the N-terminus and one is located within the conserved helicase domain. N-terminal domains probably cooperate with one another and promote the strong annealing activity of RECQ4. Surprisingly, the region spanning 322-400aa shows a very high affinity for branched DNA substrates, especially Holliday junctions. This study demonstrates biochemical activities of RECQ4 that could be involved in genome maintenance and suggest its possible role in processing replication and recombination intermediates.

Model for transport and reaction of defects and carriers within displacement cascades in gallium arsenide

A model is presented for recombination of charge carriers at evolving displacement damage in gallium arsenide, which includes clustering of the defects in atomic displacement cascades produced by neutron or ion irradiation. The carrier recombination model is based on an atomistic description of capture and emission of carriers by the defects with time evolution resulting from the migration and reaction of the defects. The physics and equations on which the model is based are presented, along with the details of the numerical methods used for their solution. The model uses a continuum description of diffusion, field-drift and reaction of carriers, and defects within a representative spherically symmetric cluster of defects. The initial radial defect profiles within the cluster were determined through pair-correlation-function analysis of the spatial distribution of defects obtained from the binary-collision code MARLOWE, using recoil energies for fission neutrons. Properties of the defects are discussed and values for their parameters are given, many of which were obtained from density functional theory. The model provides a basis for predicting the transient response of III-V heterojunction bipolar transistors to displacement damage from energetic particle irradiation.

Radial Ray Defect

A 24 days old male neonate presented to the University of Gondar Hospital with deformity at the right wrist joint since birth. Physical findings were deformity of the wrist joint with lateral deviation of fingers and absent thumb. Plain radiographs of the wrist joint showed absent radius and bones of the thumb which suggest the diagnosis of radial ray defect. Radial ray defect is a rare congenital defect that may be isolated or associated with other anomalies. This is a rare case of radial ray defect which has no association with other anomalies.

HBMP-2 and hTGF-β1 expressed in implanted BMSCs synergistically promote the repairing of segmental bone defects

ObjectiveTo evaluate the effects of co-expressing hBMP-2 and hTGF-β31 in BMSCs (bone marrow-derived mesenchymal stem cells) on the repairing process of radial segmental defects in rats. MethodsBMSCs were infected with a high titer recombinant adenovirus carrying hTGF-βl and/or hBMP-2 genes. Expression of exogenous genes in BMSCs was confirmed by RT-PCR and ELISA assays. In vitro effects of exogenous genes were assessed by MTT and ALP activity tests. A left radial defect model was created using 120 SD rats. Genetically modified or unmodified BMSCs were implanted with collagen sponge scaffolds into the 5-mm radial defect. The bone repair process was systematically monitored and evaluated by X-ray examinations, gross anatomic examinations, histological analyses, and biomechanical tests. ResultsExpression of hBMP-2 and hTGF-β1 showed synergistic effects on promoting BMSC proliferation and enhancing ALP activity in vitro. Bone repair assays showed that hBMP-2 and hTGF-β1 promoted the production of chondrocytes and osteoblasts. Implanted BMSCs transfected with both hBMP-2 and hTGF-β1 led to the best bone repair outcome.

Clinical and radiographic characterization of xenotransplantation of rat bonemarrow-derived mesenchymal stem cells for repair of radial defects of rabbit

This study aimed to evaluate the clinical and radiographic aspects of xenogenic transplantation of rat bone marrow-derived mesenchymal stem cells (MSCs) for the repair of radial bone defects of rabbit. Bone marrow derived MSCs collected from Wistar rats were expanded, differentiated, and labeled in the laboratory. In the fourth passage, the cultures were pelleted in aliquots of 107 cells/50 μL and transplanted in situ into the lesions. Thirty-six rabbits were used in the in vivo study. In all animals, defects were created by removing a bone segment of 1.0 cm in length in the right radius. The rabbits were divided into four experimental groups: the control group (CG) received percutaneously administered 50 μL of phosphate buffer (PBS) in the radial bone defect region 24 h after lesion creation; group 1 (G1) had the radial bone defect filled with absorbable gelatin sponge soaked with 50 μL of PBS during the surgery; group 2 (G2) had the radial bone defect filled with absorbable gelatin sponge soaked with the MSC pellet; and group 3 (G3) received percutaneously the MSC pellet in the radial bone defect region 24 h after lesion creation. No clinical and radiographic changes consistent with cellular rejection were observed. Percutaneous MSC xenotransplantation contributed to the repair of experimental radial bone defects.

Repairing rabbit radial defects by combining bone marrow stroma stem cells with bone scaffold material comprising a core-cladding structure.

We prepared a bone scaffold material comprising a PLGA/β-TCP core and a Type I collagen cladding, and recombined it with bone marrow stroma stem cells (BMSCs) to evaluate its potential for use in bone tissue engineering by in vivo and in vitro experiments. PLGA/β-TCP without a cladding was used for comparison. The adherence rate of the BMSCs to the scaffold was determined by cell counting. Cell proliferation rate was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. The osteogenic capability was evaluated by alkaline phosphatase activity. The scaffold materials were recombined with the BMSCs and implanted into a large segmental rabbit radial defect model to evaluate defect repair. Osteogenesis was assessed in the scaffold materials by histological and double immunofluorescence labeling, etc. The adherence number, proliferation number, and alkaline phosphatase expression of the cells on the bone scaffold material with core-cladding structure were significantly higher than the corresponding values in the PLGA/β-TCP composite scaffold material (P < 0.05). An in vivo test indicated that the bone scaffold material with core-cladding structure completely degraded at the bone defect site and bone formation was completed. The rabbit large sentimental radial defect was successfully repaired. The degradation and osteogenesis rates matched well. The bone scaffold with core-cladding structure exhibited better osteogenic activity and capacity to repair a large segmental bone defect compared to the PLGA/β-TCP composite scaffold. The bone scaffold with core-cladding structure has excellent physical properties and biocompatibility. It is an ideal scaffold material for bone tissue engineering.

Repair of large segmental bone defects in rabbits using BMP and FGF composite xenogeneic bone.

The objective of this study was to determine the ability of bone morphogenetic protein (BMP) and fibroblast growth factor (FGF) to repair large segmental radial bone defects in rabbits. We treated calf cancellous bones with 3 mg/L BMP (Group A), 5 μg/L FGF (Group B), or 3 mg/L BMP plus 5 μg/L FGF (Group C). A bone damage model was established using healthy radii from rabbits. The complexes were implanted in the areas of the bone defects in the radii. After successful transplantation, the rabbits underwent radiographic imaging, and bone graft specimens were detected by histopathology methods. Biomechanical indexes were also assessed in order to observe the healing status of the bone defects. Our results indicated that the repair of bone defects was significantly better in Group C compared to the other 2 groups. Therefore, we concluded that combining BMP and FGF significantly promoted bone defect repair and achieved effects that were superior to the use of BMP alone.

Radiological evaluation of radial bone defects treated with demineralized bone matrix in an experimental rabbit model

Radiological evaluation of radial bone defects treated with demineralized bone matrix in an experimental rabbit model

BMP2-loaded hollow hydroxyapatite microspheres exhibit enhanced osteoinduction and osteogenicity in large bone defects.

The regeneration of large bone defects is an osteoinductive, osteoconductive, and osteogenic process that often requires a bone graft for support. Limitations associated with naturally autogenic or allogenic bone grafts have demonstrated the need for synthetic substitutes. The present study investigates the feasibility of using novel hollow hydroxyapatite microspheres as an osteoconductive matrix and a carrier for controlled local delivery of bone morphogenetic protein 2 (BMP2), a potent osteogenic inducer of bone regeneration. Hollow hydroxyapatite microspheres (100±25 μm) with a core (60±18 μm) and a mesoporous shell (180±42 m2/g surface area) were prepared by a glass conversion technique and loaded with recombinant human BMP2 (1 μg/mg). There was a gentle burst release of BMP2 from microspheres into the surrounding phosphate-buffered saline in vitro within the initial 48 hours, and continued at a low rate for over 40 days. In comparison with hollow hydroxyapatite microspheres without BMP2 or soluble BMP2 without a carrier, BMP2-loaded hollow hydroxyapatite microspheres had a significantly enhanced capacity to reconstitute radial bone defects in rabbit, as shown by increased serum alkaline phosphatase; quick and complete new bone formation within 12 weeks; and great biomechanical flexural strength. These results indicate that BMP2-loaded hollow hydroxyapatite microspheres could be a potential new option for bone graft substitutes in bone regeneration.

Oxaloacetate acetylhydrolase gene mutants of Sclerotinia sclerotiorum do not accumulate oxalic acid, but do produce limited lesions on host plants.

The oxaloacetate acetylhydrolase (OAH, EC 3.7.1.1)-encoding gene Ss-oah1 was cloned and functionally characterized from Sclerotinia sclerotiorum. Ss-oah1 transcript accumulation mirrored oxalic acid (OA) accumulation with neutral pH induction dependent on the pH-responsive transcriptional regulator Ss-Pac1. Unlike previously characterized ultraviolet (UV)-induced oxalate-deficient mutants ('A' mutants) which retain the capacity to accumulate OA, gene deletion Δss-oah1 mutants did not accumulate OA in culture or during plant infection. This defect in OA accumulation was fully restored on reintroduction of the wild-type (WT) Ss-oah1 gene. The Δss-oah1 mutants were also deficient in compound appressorium and sclerotium development and exhibited a severe radial growth defect on medium buffered at neutral pH. On a variety of plant hosts, the Δss-oah1 mutants established very restricted lesions in which the infectious hyphae gradually lost viability. Cytological comparisons of WT and Δss-oah1 infections revealed low and no OA accumulation, respectively, in subcuticular hyphae. Both WT and mutant hyphae exhibited a transient association with viable host epidermal cells at the infection front. In summary, our experimental data establish a critical requirement for OAH activity in S. sclerotiorum OA biogenesis and pathogenesis, but also suggest that factors independent of OA contribute to the establishment of primary lesions.

The Effect of Capitellar Impaction Fractures on Radiocapitellar Stability

To determine the effect of capitellar impaction fractures on radiocapitellar stability in a model that simulated a terrible triad injury. Six cadaveric elbows were dissected free of skin and muscles. Tendons were preserved. The lateral collateral ligament was released and repaired (surgical control). Two sizes of capitellar impaction defects were created. After lateral collateral ligament release and repair, we then sequentially created osseous components of a terrible triad injury (partial radial head resection and coronoid fracture) through an olecranon osteotomy that was fixed with a plate. Radiocapitellar stability was recorded after the creation of each new condition. Significantly less force was required for radiocapitellar subluxation after the creation of 20° and 40° capitellar defects compared with the surgical control (intact capitellum). After the addition of a Mason type II radial head defect and then a coronoid defect, stability decreased significantly further. Impaction fractures of the distal portion of the capitellum may contribute to a loss of radiocapitellar stability, particularly in an elbow fracture-dislocation. Because these injuries may be unrecognized, consideration should be given to diagnosing and addressing them.