Radial Defects Research Articles

Comparison of osteogenesis of bovine bone xenografts between true bone ceramics and decalcified bone matrix

Xenograft bone scaffolds have certain advantages such as mechanical strength, osteoinductive properties, sufficient source and safety. This study aimed to compare osteogenesis of the two main bovine bone xenografts namely true bone ceramics (TBC) and decalcified bone matrix (DBM), and TBC or DBM combined with bone morphogenetic protein (BMP)-2 (TBC&BMP-2 and DBM&BMP-2). The characteristics of TBC and DBM were investigated by observing the appearance and scanning electron microscopic images, examining mechanical strength, evaluating cytotoxicity and detecting BMP-2 release after being combined with BMP-2 in vitro. The femoral condyle defect and radial defect models were successively established to evaluate the performance of the proposed scaffolds in repairing cortical and cancellous bone defects. General observation, hematoxylin and eosin (HE) staining, mirco-CT scanning, calcein double labeling, X-ray film observation, three-point bending test in vivo were then performed. It indicated that the repair with xenograft bone scaffolds of 8 weeks were needed and the repair results were better than those of 4 weeks whatever the type of defects. To femoral condyle defect, TBC and TBC&BMP-2 were better than DBM and DBM&BMP-2, and TBC&BMP-2 was better than TBC alone; to radial defect, DBM and DBM&BMP-2 were better than TBC and TBC&BMP-2, and DBM&BMP-2 was better than DBM alone. This study has shown that TBC and DBM xenograft scaffolds can be more suitable for the repair of cancellous bone and cortical bone defects for 8 weeks in rats, respectively. We also have exhibited the use of BMP-2 in combination with DBM or TBC provides the possibility to treat bone defects more effectively. We thus believe that we probably need to select the more suitable scaffold according to bone defect types, and both TBC and DBM are promising xenograft materials for bone tissue engineering and regenerative medicine.Graphical abstract

Decellularized xenogenic bone graft for repair of segmental bone defect in rabbits.

Bone grafting is a preferred treatment option for the healing of large diaphyseal bone defects and is useful in the management of nonunion, delayed union, and tumor resection. To investigate a decellularization protocol of bovine cancellous bone for xenogenic implantation in radial bone defects in rabbits. Bovine bone scaffolds fabricated with various decellularization protocols viz phosphate buffer saline (PBS), 1% sodium dodecyl sulfate (SDS), and rapid freeze and thaw technique. The manufactured scaffolds were characterized by biomechanical testing, histological staining, and scanning electron microscopy. A 10 mm rabbit radius bone defect was repaired with autograft and SDS treated and rapid freeze and thaw in groups A, B, and C respectively. Healing was evaluated by radiography and histopathology at 0, 30, 60, and 90 days. The grafts were also checked for host tissue reaction and incorporation into the defect. The freeze and thaw group showed complete elimination of all cellular nuclei, regular arrangement of collagen fiber, and no significant difference in tensile strength compared to 1% SDS treated and native groups. The in vivo radiographic and histopathological study showed that the rapid freeze and thaw group had complete bridging of the bone gap defect with new bone formation and they were immunologically less reactive compared to group B. The in vitro and in vivo evaluation of the grafts suggested that freeze and thaw technique was most superior to all other techniques for effective decellularization and augmentation of bone healing with better integration of the graft into the host.

Closure of radial forearm free flap donor-site defect with proportional local full-thickness skin graft: case series study of a new design.

ObjectivesThe aim of this study was to describe a simple, convenient, and reliable new technique using local full-thickness skin graft (FTSG) for skin coverage of a donor-site defect of the radial forearm free flap (RFFF).Patients and Methods Between April 2016 and April 2021, five patients with oral squamous cell carcinoma underwent mass resection combined with RFFF reconstruction. After RFFF harvesting, donor-site defects were restored by proportional local FTSG.ResultsThe donor-site defects ranged in size from 24 to 41.25 cm2, with a mean of 33.05 cm2. Good or acceptable esthetic outcomes were obtained in all five patients. There was no dehiscence, skin necrosis, wound infection, or severe scarring at the graft site through the end of the postoperative follow-up period, and no patient had any specific functional complaint.ConclusionThe proportional local FTSG showed promising results for skin coverage of the donor-site defect of the RFFF. This technique could decrease the need for skin grafts from other sites.

3D printing of polycaprolactone/bioactive glass composite scaffolds for in situ bone repair

3D printing technology can fabricate customized scaffolds based on patient-derived medical images, so it has attracted much attention in the field of developing bone repair scaffolds. Polycaprolactone (PCL) is a suitable polymer for preparing bone repair scaffolds because of its good biocompatibility, thermal stability, excellent mechanical properties and degradable properties. However, PCL is a bioinert material and cannot induce new bone formation at the defect site. In this study, the bioactive material 58s bioactive glass was mixed into PCL to form PCL/bioactive glass composite material. The results of contact angle showed that the hydrophilicity of the scaffold was significantly enhanced with the increase of bioactive glass content. In vitro experiment results showed that, with the increase of bioactive glass content, cell adhesion and proliferation were enhanced, the expression levels of Runx2 and Collagen I(COL-I) were upregulated. The experimental results of in vivo radial defect repair in rats also showed that the effect of bone repair was improved with the increase of bioactive glass content. In conclusion, PCL customized bone repair scaffold containing 20% bioactive glass has widely potential used in the field of clinical bone repair.

Distinct roles for the Charcot-Marie-Tooth disease-causing endosomal regulators Mtmr5 and Mtmr13 in axon radial sorting and Schwann cell myelination.

The form of Charcot-Marie-Tooth type 4B (CMT4B) disease caused by mutations in myotubularin-related 5 (MTMR5; also called SET binding factor 1, SBF1) shows a spectrum of axonal and demyelinating nerve phenotypes. This contrasts with the CMT4B subtypes caused by MTMR2 or MTMR13 (SBF2) mutations, which are characterized by myelin outfoldings and classic demyelination. Thus, it is unclear whether MTMR5 plays an analogous or distinct role from that of its homolog, MTMR13, in the peripheral nervous system (PNS). MTMR5 and MTMR13 are pseudophosphatases predicted to regulate endosomal trafficking by activating Rab GTPases and binding to the phosphoinositide 3-phosphatase MTMR2. In the mouse PNS, Mtmr2 was required to maintain wild-type levels of Mtmr5 and Mtmr13, suggesting that these factors function in discrete protein complexes. Genetic elimination of both Mtmr5 and Mtmr13 in mice led to perinatal lethality, indicating that the two proteins have partially redundant functions during embryogenesis. Loss of Mtmr5 in mice did not cause CMT4B-like myelin outfoldings. However, adult Mtmr5-/- mouse nerves contained fewer myelinated axons than control nerves, likely as a result of axon radial sorting defects. Consistently, Mtmr5 levels were highest during axon radial sorting and fell sharply after postnatal day seven. Our findings suggest that Mtmr5 and Mtmr13 ensure proper axon radial sorting and Schwann cell myelination, respectively, perhaps through their direct interactions with Mtmr2. This study enhances our understanding of the non-redundant roles of the endosomal regulators MTMR5 and MTMR13 during normal peripheral nerve development and disease.

Endochondral Bone Tissue Engineering Using Human Induced Pluripotent Stem Cells

The use of induced pluripotent stem cells (iPSCs) shows potential in bone regenerative strategies. In this study, we investigated whether implantation of chondrogenically differentiated iPSC-derived mesenchymal stem cells (iMSCs) can lead to successful bone regeneration in nude mice with bone defects. Two human iPSC clones (201B7 and 454E2) were used. After generating iMSCs, chondrogenic differentiation was achieved by three-dimensional pellet culture. Thereafter, a 2-mm defect was created in the radius of nude mice, and chondrogenically differentiated iMSC pellets were transplanted in the defect. Microcomputed tomography imaging was performed 8 weeks posttransplantation to assess bone regeneration. All (100%) radii in the 201B7 cell-derived pellet transplantation group and 7 of 10 (70%) radii in the 454E2 cell-derived pellet transplantation group showed bone union. In contrast, 2 of 11 radii (18%) in the control group showed bone union. Thus, the experimental groups showed significantly higher bone union rates than the control group (p < 0.05). Histological analysis 2 weeks postimplantation in the experimental groups revealed hypertrophic chondrocytes within grafted iMSC pellets and the formation of woven bone around them. This hypertrophic chondrocyte transitioning to newly formed bone suggests that the cartilaginous template can trigger endochondral bone ossification (ECO). Four weeks postimplantation, the cartilage template was reduced in size; newly formed woven bone was predominant in the defect site. New vessels were surrounded by a matrix of woven bone, and hypertrophic chondrocytes transitioning to newly formed bone indicated the progression of ECO. Eight weeks postimplantation, the pellets were completely resorbed and replaced by bone; complete bone union was observed. Dense mature bone developed with evidence of lamellar-like bone formation. Collectively, our results suggest that using iMSC-based cartilage grafts recapitulating the morphogenetic process of ECO in the context of embryonic skeletogenesis is a promising strategy for repairing large bone defects. Impact statement We investigated whether implantation of chondrogenically differentiated iPSC-derived mesenchymal stem cells (iMSCs) could lead to the successful regeneration of bone defects in vivo. We implanted two different clones of human induced pluripotent stem cells into a radial bone defect model. Eleven of 11 (100%) and 7 of 10 (70%) radii in the 201B7 and 454E2 cell-derived pellet transplantation groups, respectively, showed bone union, which were significantly higher than those in the control group [only 2 of 11 radii (18%)]. Overall, our results support the use of iMSC-based cartilage grafts recapitulating the morphogenetic process of endochondral bone ossification for repairing large bone defects.

Mussel-Inspired Gold Nanoparticle and PLGA/L-Lysine-g-Graphene Oxide Composite Scaffolds for Bone Defect Repair.

PurposeInsufficient biological activity heavily restricts the application and development of biodegradable bone implants. Functional modification of bone implants is critical to improve osseointegration and bone regeneration.MethodsIn this study, L-lysine functionalized graphene oxide (Lys-g-GO) nanoparticles and polydopamine-assisted gold nanoparticle (AuNPs-PDA) coatings were applied to improve the biological function of PLGA scaffold materials. The effects of Lys-g-GO nanoparticles and AuNPs-PDA functionalized coatings on the physicochemical properties of PLGA scaffolds were detected with scanning electron microscopy (SEM), contact angle measurement, and mechanical testing instruments. In vitro, the effects of composite scaffolds on MC3T3-E1 cell proliferation, adhesion, and osteogenic differentiation were studied. Finally, a radial defect model was used to assess the effect of composite scaffolds on bone defect healing.ResultsThe prepared AuNPs-PDA@PLGA/Lys-g-GO composite scaffolds exhibited excellent mechanical strength, hydrophilicity and antibacterial properties. In vitro, this composite scaffold can significantly improve osteoblast adhesion, proliferation, osteogenic differentiation, calcium deposition, and other cell behaviour. In vivo, this composite scaffold can significantly promote the new bone formation and collagen deposition in the radial defect site and presented good biocompatibility.ConclusionThe combination of bioactive nanoparticles and surface coatings shows considerable potential to enhance the osseointegration of bone implants.

Effects of Combination of BMP7, PFG, and Autograft on Healing of the Experimental Critical Radial Bone Defect by Induced Membrane (Masquelet) Technique in Rabbit.

Healing of large segmental bone defects can be challenging for orthopedic surgeons. This research was conducted to provide further insight into the effects of BMP7 in combination with autograft and platelet fibrin glue (PFG) on bone regeneration by Masquelet technique (MT). Twenty five domestic male rabbits, more than 6 months old, weighing 2.00±0.25 kg were randomly divided into five equal groups as follows: MT-blank cavity (without any biological or synthetic materials) (1), blank cavity (2), MT-autograft (3), MT-autograft-BMP7 (4), and MT-BMP7-PFG (5). A 20 mm segmental defect was made in radial bone in both forelimbs. The Masquelet technique was done in all groups except group 2. The study was evaluated by radiology, biomechanics, histopathology and scanning electron microscopy. The results showed that Masquelet technique enhanced the healing process, as, the structural and functional criteria of the injured bone showed significantly improved bone healing (P<0.05). Treatment by PFG-BMP7, Autograft-BMP7, and autograft demonstrated beneficial effects on bone healing. However, Autograft-BMP7 was more effective than autograft in healing of the radial defect in rabbits. Our findings introduce the osteogenic materials in combination with Masquelet technique as an alternative for reconstruction of the big diaphyseal defects in the long bones in animal models. Our findings may be useful for clinical application in future.

Retraction Note to: Mesenchymal stem cells seeded onto tissue-engineered osteoinductive scaffolds enhance the healing process of critical-sized radial bone defects in rat.

Long bone defects comprise one of the most prevalent clinical problems worldwide and the current bone grafting materials have major limitations to repair them. Although tremendous efforts have been made to repair critical-sized long bone defects in animal models, designing an optimal bone tissue-engineered substitute remains one of the main challenges. Hence, this study aims to closely mimic a natural bone healing process by a tissue-engineered construct including osteoinductive materials pre-seeded with bone marrow-derived mesenchymal stem cells (BMSCs). Bioactive glass (BG) was incorporated into the gelatin/nano-hydroxyapatite (G/nHAp) scaffold (conventional one) to improve the bone regeneration process via its osteoinductivity and angiogenic activity. The fabricated G/nHAp and gelatin/nano-hydroxyapatite/bioactive glass (G/nHAp/BG) scaffolds were characterized by X-ray diffraction (XRD) and scanning electron microscopy (SEM) and analyzed for porosity and degradation rate. The osteogenic capability of fabricated scaffolds with or without BMSCs was then evaluated in vitro and in vivo. Critical-sized radial bone defects in rats were randomly filled with cell-free and BMSC-seeded scaffolds, autograft and a group left empty without any treatment. In vitro analysis showed that the G/nHAp/BG scaffold significantly increased the expression level of osteogenic and angiogenic markers in comparison to the G/nHAp-treated and control groups (P < 0.05). Moreover, the defects treated with the BMSC-seeded scaffolds showed superior bone formation and structural properties compared to the cell-free scaffolds 4 and 12 weeks post surgery. The radiological and histomorphological properties of defects treated by BMSC-seeded scaffolds, especially the BMSC-seeded G/nHAp/BG scaffold, were comparable to those of the autograft group. It is concluded that the combination of osteoconductive materials (i.e., nHAp) with the bioactive ones such as bioactive glass can effectively accelerate the bone regeneration process. In addition, our results demonstrated that the BMSCs have the potential to drastically increase the bone regeneration ability of osteoinductive scaffolds.

A Double-Barreled Fibular Graft for the Reconstruction of Both Forearm Bones and Humeroradial Joint after a Tumor Resection.

A double-barreled fibular graft was used to reconstruct both forearm bones and the humeroradial joint after tumor resection. The patient had a tumor of radius that invaded the ulna and extensor groups. After a wide tumor resection, vascularized fibular autograft and soft tissue reconstruction was performed. A fibular graft were placed as a double barrel in the proximal ulnar and radial defects including the radial head and fixed using two locking plates. Simultaneously, reconstruction of the humeroradial joint and wrist dorsiflexion was performed. Two years postoperatively, the patient is satisfied with his elbow function while performing activities of daily living. Although amputation was one of the options considered during the preoperative planning in this case, the affected limb could be preserved by grafting a double-barreled fibula and tendon transfer, which could maintain the function of his upper left limb.

Requirement of CRMP2 Phosphorylation in Neuronal Migration of Developing Mouse Cerebral Cortex and Hippocampus and Redundant Roles of CRMP1 and CRMP4.

The mammalian cerebral cortex is characterized by a 6-layer structure, and proper neuronal migration is critical for its formation. Cyclin-dependent kinase 5 (Cdk5) has been shown to be a critical kinase for neuronal migration. Several Cdk5 substrates have been suggested to be involved in ordered neuronal migration. However, in vivo loss-of-function studies on the function of Cdk5 phosphorylation substrates in neuronal migration in the developing cerebral cortex have not been reported. In this study, we demonstrated that Cdk5-mediated phosphorylation of collapsing mediator protein (CRMP) 2 is critical for neuronal migration in the developing cerebral cortex with redundant functions of CRMP1 and CRMP4. The cerebral cortices of triple-mutant CRMP1 knock-out (KO); CRMP2 knock-in (KI)/KI; and CRMP4 KO mice showed disturbed positioning of layers II-V neurons in the cerebral cortex. Further experiments using bromodeoxyuridine birthdate-labeling and in utero electroporation implicated radial migration defects in cortical neurons. Ectopic neurons were detected around the CA1 region and dentate gyrus in CRMP1 KO; CRMP2 KI/KI; and CRMP4 KO mice. These results suggest the importance of CRMP2 phosphorylation by Cdk5 and redundancy of CRMP1 and CRMP4 in proper neuronal migration in the developing cerebral cortex and hippocampus.

Anomalous Lehmann Rotation of Achiral Nematic Liquid Crystal Droplets Trapped under Linearly Polarized Optical Tweezers

Continuous rotation of a cholesteric droplet under the heat gradient was observed by Lehmann in 1900. This phenomenon, the so-called Lehmann effect, consists of unidirectional rotation around the heat flux axis. We investigate this gradient heat effect using infrared laser optical tweezers. By applying single trap linearly polarized optical tweezers onto a radial achiral nematic liquid crystal droplet, trapping of the droplet was performed. However, under a linearly polarized optical trap, instead of stable trapping of the droplet with slightly deformed molecular directors along with a radial hedgehog defect, anomalous continuous rotation of the droplet was observed. Under low power laser trapping, the droplet appeared to rotate clockwise. By continuously increasing the laser power, a stable trap was observed, followed by reverse directional rotation in a higher intensity laser trap. Optical levitation of the droplet in the laser beam caused the heat gradient, and a breaking of the symmetry of the achiral nematic droplet. These two effects together led to the rotation of the droplet under linearly polarized laser trapping, with the sense of rotation depending on laser power.

A mechanism coordinating root elongation, endodermal differentiation, redox homeostasis and stress response.

Root growth relies on both cell division and cell elongation, which occur in the meristem and elongation zones, respectively. SCARECROW (SCR) and SHORT-ROOT (SHR) are GRAS family genes essential for root growth and radial patterning in the Arabidopsis root. Previous studies showed that SCR and SHR promote root growth by suppressing cytokinin response in the meristem, but there is evidence that SCR expressed beyond the meristem is also required for root growth. Here we report a previously unknown role for SCR in promoting cell elongation. Consistent with this, we found that the scr mutant accumulated a higher level of reactive oxygen species (ROS) in the elongation zone, which is probably due to decreased expression of peroxidase gene 3, which consumes hydrogen peroxide in a reaction leading to Casparian strip formation. When the oxidative stress response was blocked in the scr mutant by mutation in ABSCISIC ACID 2 (ABA2) or when the redox status was ameliorated by the upbeat 1 (upb1) mutant, the root became significantly longer, with longer cells and a larger and more mitotically active meristem. Remarkably, however, the stem cell and radial patterning defects in the double mutants still persisted. Since ROS and peroxidases are essential for endodermal differentiation, these results suggest that SCR plays a role in coordinating cell elongation, endodermal differentiation, redox homeostasis and oxidative stress response in the root. We also provide evidence that this role of SCR is independent of SHR, even though they function similarly in other aspects of root growth and development.

Comparison capacity of collagen hydrogel, mix-powder and in situ hydroxyapatite/collagen hydrogelscaffolds with and without mesenchymal stem cells and platelet-rich plasma in regeneration of critical sized bone defect in a rabbit animal model.

The aim of this study was to investigate the effect of developed collagen (Co) hydrogel (CH), powder-mixed hydroxyapatite/collagen (HA/Co) hydrogel and in situ synthesized HA/Co (In/HA/Co) hydrogel with or without mesenchymal stem cell (MSC) and platelet-rich plasma (PRP) on the regeneration of full-thickness critical size bone defect in the rabbit animal model. In the first step of this study, the scaffolds were synthesized and characterized using FTIR spectroscopy, X-ray diffraction, and scanning electron microcopy. In the second step or animal study, the radial bone defects were filled with the synthesized scaffolds with and without MSC and PRP. One hundred sixty one year-old New Zealand white male rabbits were randomly divided in 16 groups of 10 rabbits including control with bone defect without treatment, In/HA/Co, HA/Co, CH, PRP, MSC, CH + PRP, HA/Co, In/HA/Co+ PRP, HA/Co + PRP, CH + MSC, In/HA/Co+ MSC, HA/Co + MSC, CH + PRP + MSC, In/HA/Co+ PRP + MSC, and HA/Co + PRP + MSC. The created defects were filled using the constructed scaffolds alone or seeded with MSCs, with and without PRP injection. The treatments were assessed using histopathological, immunohistochemical and rediographical analysis on days 14, 28, 42, 56 post-treatment. The plate-like HA particles were distributed homogeneously in the in situ HA/Co scaffold compared to the HA/Co scaffold and had a similar structure to bone with carbonated plate-like HA particles and nanofibrilated Co matrix. In situ HA/Co nanocomposite seeded with MSC and enriched by PRP can accelerate bone regeneration resulted from osteoblastic production of osteocalcin protein. Therefore, in situ HA/Co hydrogel seeded with MSC and PRP can be a new approach for bone tissue engineering.

Bone defects are repaired by enhanced osteogenic activity of the induced membrane: a case report and literature review

BackgroundThe induced membrane technique (IMT) is an effective strategy to repair bone defects and involves a two-stage set of surgical procedures. Although the IM has osteogenic activity, bone grafting is necessary in standard IMT. Bone defects repaired completely by osteogenic activity of the IM alone without bone grafts are rare.Case presentationWe present a case of infected fractures and bone defects of the ulna and radius treated with IMT. After the first stage using polymethylmethacrylate (PMMA) beads, X-rays showed that new callus developed after 2 to 4 months, and the defects were repaired completely by 5 months. We also present a literature review on spontaneous osteogenesis of the IM in patients.ConclusionsWe present a case of infected ulnar and radial bone defects that healed by 5 months after the first stage of the IMT using a PMMA spacer. This finding suggests that local associated inflammatory reactions and bone tissue might enhance the osteogenic activity of the IM, causing spontaneous healing of bone defects. This appears to be the first such case reported in the literature.

Growth Hormone Deficiency: Extending the Phenotypic Spectrum of SALL4-Related Disorders

Background: The SALL4 gene encodes sal-like protein 4, a transcription factor with eight zinc finger motifs that is essential for the development of the epiblast and primitive endoderm. In association with TBX5 (T-box), SALL4 is responsible for the establishment and morphogenesis of the thumb. Pathogenic SALL4 variants have been reported to cause Duane-radial ray syndrome (also known as Okihiro syndrome), acro-renal-ocular syndrome and Holt-Oram syndrome. Hereby, we report on a family with radial hypoplasia and kidney dystopia in members of 4 consecutive generations, and short stature due to growth hormone deficiency (GHD) in the proband. Clinical Case: The male proband was born from the 3rd normal pregnancy at 39th week of gestation. He has no biological siblings. He was born small for gestational age (birth weight 2550 g, length 47 cm - both < 2SD) and had bilateral asymmetrical radial ray malformation consisting of radial hypoplasia, ulnar flexure and bilateral aplasia of the thumb, and pelvic dystopia of his right kidney. He had no cardiac malformations, clubfoot, ocular coloboma or Duane anomaly. He was examined for progressive short stature at the age of 3.9 years, where his IGF-1 was 68 ug/l (-1.0 SD), and peak GH in two stimulation tests was 6.2 ug/l. Other pituitary hormones were normal. His mother’s and father’s heights are 152.3 cm (-2.4 SD), and 177.8 cm (-0.4 SD), respectively. His father has malformation of the forearm that is milder than that of the son. The paternal grandfather is affected as well, with a radial defect with missing opposition of the thumb and height 164 cm (-2.3 SD). The family reports that the phenotype of radial dysplasia was apparent in the paternal grandfather’s mother as well. Due to the suggestive monogenic dominant transmission of the developmental abnormality, we carried out whole exome sequencing that revealed a nonsense variant in the SALL4 gene c.1717C>T (p.Arg573Ter) in the proband, his father, and paternal grandfather. The proband was started with regular GH therapy at age 6.5 years and experienced catch-up growth as expected in GHD. By the age 11 years, his height stabilized at about the 25th percentile in accordance to the mid-parent height with a target height of 171.5 +/- 8.5 cm. Puberty started spontaneously at the age 12.5 years. Conclusion: This is the first case demonstrating a patient with a congenital upper limb defect based on a pathogenic variant of the SALL4 gene where an isolated growth hormone deficiency (GHD) was detected and has been successfully treated with growth hormone. Acknowledgements: Genetic testing was funded by AZV grant NV18-07-00283.

Rare case report of anorectal malformation and intestinal atresia.

IntroductionIntestinal malformations, such as intestinal atresia, malrotation, and anorectal malformation, are rare events, but concurrent intestinal atresia and anorectal malformation are rare in combination. These anomalies have similar in utero and perinatal symptoms, which can make the diagnosis of both defects prenatally challenging.Presentation of caseWe present a case of a male infant with a prenatal diagnosis of truncus arteriosus who on a 32-week routine prenatal ultrasound was suspected to have an intestinal malformation. On day of life one, the patient was taken to the operating room and found to have both type IIIa ileal atresia and anorectal malformation with normal bowel in between. A complete work up for vertebral defects, anorectal malformation, cardiac septal defects, esophageal atresia, renal anomalies, and radial limb defects (VACTERL) anomalies did not reveal additional anomalies.DiscussionIn this case, prenatal information supported intestinal obstruction, and the rare combination of both intestinal atresia and anorectal malformation proved surprising and interesting.ConclusionWe suggest providers be aware of the potential of multiple alimentary tract malformations to improve operative preparation and reduce the morbidity or mortality risk from repeat procedures when possible.

In Vivo Evaluation of the Regenerative Capability of Glycylglycine Ethyl Ester-Substituted Polyphosphazene and Poly(lactic-co-glycolic acid) Blends: A Rabbit Critical-Sized Bone Defect Model.

In an effort to understand the biological capability of polyphosphazene-based polymers, three-dimensional biomimetic bone scaffolds were fabricated using the blends of poly[(glycine ethylglycinato)75(phenylphenoxy)25]phosphazene (PNGEGPhPh) and poly(lactic-co-glycolic acid) (PLGA), and an in vivo evaluation was performed in a rabbit critical-sized bone defect model. The matrices constructed from PNGEGPhPh-PLGA blends were surgically implanted into 15 mm critical-sized radial defects of the rabbits as structural templates for bone tissue regeneration. PLGA, which is the most commonly used synthetic bone graft substitute, was used as a control in this study. Radiological and histological analyses demonstrated that PNGEGPhPh-PLGA blends exhibited favorable in vivo biocompatibility and osteoconductivity, as the newly designed matrices allowed new bone formation to occur without adverse immunoreactions. The X-ray images of the blends showed higher levels of radiodensity than that of the pristine PLGA, indicating higher rates of new bone formation and regeneration. Micro-computed tomography quantification revealed that new bone volume fractions were significantly higher for the PNGEGPhPh-PLGA blends than for the PLGA controls after 4 weeks. The new bone volume increased linearly with increasing time points, with the new tissues observed throughout the defect area for the blend and only at the implant site's extremes for the PLGA control. Histologically, the polyphosphazene system appeared to show tissue responses and bone ingrowths superior to PLGA. By the end of the study, the defects with PNGEGPhPh-PLGA scaffolds exhibited evidence of effective bone tissue ingrowth and minimal inflammatory responses. Thus, polyphosphazene-containing biomaterials have excellent translational potential for use in bone regenerative engineering applications.

Lateral Meniscus Posterior Root Injury: MRI Findings in Children With Anterior Cruciate Ligament Tear.

BACKGROUND. Undiagnosed and unrepaired root tears are increasingly recognized as a preventable cause of accelerated osteoarthritis. Preoperative MRI findings of lateral meniscus posterior root tears in children with concomitant anterior cruciate ligament (ACL) injury are not well described. OBJECTIVE. The purpose of this study was to investigate the performance of preoperative MRI for identifying concomitant lateral meniscus posterior root injuries in pediatric patients with ACL tears with arthroscopy as the reference standard. METHODS. Consecutively registered children who underwent MRI within 90 days before arthroscopic primary ACL reconstruction between March 2017 and December 2019 were included. Two radiologists assessed MRI examinations for direct signs involving the root proper and for findings associated with lateral meniscus posterior root tears. Kappa coefficients for MRI findings were computed. Findings in patients with root tears and intact roots were compared by independent-samples t test, Mann-Whitney U test, chi-square test, Fisher exact test, and multivariable logistic regression analysis. RESULTS. At arthroscopy, 39 children (18 boys, 21 girls; mean age, 15.2 ± 1.4 years) had lateral meniscus posterior root tears; 51 (22 boys, 29 girls; mean age, 15.7 ± 1.8 years) had intact roots. Kappa coefficients ranged from 0.65 to 0.92, aside from tears involving the entheseal segment (κ = 0.55) or popliteomeniscal fascicles (κ = 0.45). MRI findings that were predictors of arthroscopically diagnosed root tear (p < .05) were lateral meniscus root tear in any segment (odds ratio [OR], 16.8; 95% CI, 5.6-50.1), degeneration in any segment (OR, 3.9; 95% CI, 1.6-9.6), coronal cleft sign (OR, 5.7; 95% CI, 2.0-16.7), sagittal ghost sign (OR, 4.8; 95% CI, 1.2-19.1), and axial radial defect sign (OR, 7.1; 95% CI, 2.4-20.5). Tear involving any segment of the root proper had the highest PPV, 82%, with 79% NPV. The coronal cleft, sagittal ghost, and axial radial defect signs had specificities of 88%, 94%, and 88% but sensitivities of 44%, 23%, and 49%. The only significant independent predictor on preoperative MRI was root tear in any segment (OR, 15.8; 95% CI, 2.7-137.5; p = .003). CONCLUSION. Among MRI findings evaluated for preoperative diagnosis of lateral meniscus posterior root tear, tear involving any segment of the root proper had the strongest performance; associated findings had high specificity but low sensitivity. CLINICAL IMPACT. Accurate identification of lateral meniscus posterior root tears on preoperative MRI can aid in operative planning and reduce treatment delay.

Ionically Charged Topological Defects in Nematic Fluids

Charge profiles in liquid electrolytes are of crucial importance for applications, such as supercapacitors, fuel cells, batteries, or the self-assembly of particles in colloidal or biological settings. However, creating localised (screened) charge profiles in the bulk of such electrolytes, generally requires the presence of surfaces -- for example, provided by colloidal particles or outer surfaces of the material -- which poses a fundamental constraint on the material design. Here, we show that topological defects in nematic electrolytes can perform as regions for local charge separation, forming charged defect cores and in some geometries even electric multilayers, as opposed to the electric double layers found in isotropic electrolytes. Using a Landau-de Gennes-Poisson-Boltzmann theoretical framework, we show that ions highly effectively couple with the topological defect cores via ion solvability, and with the local director-field distortions of the defects via flexoelectricity. The defect charging is shown for different defect types -- lines, points, and walls -- using geometries of ionically screened flat isotropic-nematic interfaces, radial hedgehog point defects and half-integer wedge disclinations in the bulk and as stabilised by (charged) colloidal particles. More generally, our findings are relevant for possible applications where topological defects act as diffuse ionic capacitors or as ionic charge carriers.