Right-sided Defects Research Articles

Prenatal Congenital Heart Disease and Placental Phenotypes: Preserved Neonatal Weight Despite Small Placentas

BackgroundCongenital heart disease (CHD) affects 8 in 1,000 live births with significant postnatal implications including growth failure, neurodevelopmental delay, and mortality. The placenta develops concomitantly with the fetal heart. High rates of placental pathology and discordant growth in pregnancies affected by CHD highlight the significance of the fetal-placental-cardiac axis. ObjectivesThis study aimed to characterize the relationship between neonatal birthweight (BW), head circumference, placental weight (PW), and placental pathology in pregnancies affected by CHD. PW:BW provides a surrogate to assess placental efficiency, or nutrient exchange and delivery by the placenta, across CHD phenotypes. MethodsRetrospective cohort of 139 live-born singletons with postnatally confirmed CHD with placental pathology. Placental examination, infant BW, head circumference, and CHD categories (septal defects, right-sided defects, left-sided defects, conotruncal anomalies, and others) were included. Chi-square, Fisher’s exact, or Kruskall-Wallis tests and multinomial logistic regressions, as appropriate. ResultsMedian birthweight and head circumference percentile was 33 and 35, respectively. Placental pathology was documented in 37% of cases. PW to BW ratios were <10th percentile for 78% and <3rd percentile for 54% of the cohort, with no difference between CHD categories (P = 0.39 and P = 0.56, respectively). ConclusionsInfants with CHD have preserved BW and head circumferences in the setting of small placentas and increased prevalence of placental pathology, suggesting placental efficiency. Detection of abnormal placental growth could add prenatal diagnostic value. Placental and neonatal discordant growth may allude to a vascular anomaly predisposing fetuses to developing CHD. Further studies are needed to explore fetal nutrient delivery and utilization efficiency.

Congenital diaphragmatic hernia survival in an English regional ECMO center

IntroductionCongenital diaphragmatic hernia (CDH) remains a cause of neonatal death. Our aims are to describe contemporary rates of survival and the variables associated with this outcome, contrasting these with our...

Congenital Diaphragmatic Hernia: An Update on Management Strategies and Outcomes

Congenital diaphragmatic hernia (CDH) is a severe developmental anomaly associated with high mortality and long-term morbidity. Right-sided defects (RCDH) are less common than left-sided (LCDH) with variable outcomes and survival rates reported in the literature that are more frequently worse than for infants with left hernias

MRI diagnosis of spontaneous intraventricular tension-pneumocephalus in a 10-month-old male Saarloos Wolfdog.

A 10-month-old male Saarloos Wolfdog was presented with a history of multiple neurologic deficits that had acutely progressed. Neurologic examination findings localized signs to the cerebrum and brainstem. Magnetic resonance imaging revealed markedly enlarged and gas-filled lateral ventricles with a mass effect leading to cerebellar herniation. A right-sided defect of the cribriform plate with a dysplastic ethmoturbinate was identified as the inlet of air and origin of the intraventricular tension pneumocephalus. Surgical findings were consistent with a ruptured, congenital, nasal meningocele.

Long-term outcomes of congenital diaphragmatic hernia: A single institution experience

Background/PurposeAs survival rates for patients with congenital diaphragmatic hernia (CDH) increase, long-term sequelae become increasingly prevalent. We present the outcomes of patients who underwent CDH repair at our institution and discuss standardization of follow-up care in our long-term multidisciplinary follow-up clinic. MethodsA retrospective review of patients followed in multidisciplinary clinic after CDH repair at our institution from January 1, 2005 to December 1, 2020. ResultsA total of 193 patients met inclusion criteria, 73 females (37.8%) and 120 males (62.2%). Left-sided defects were most common (75.7%), followed by right-sided defects (20.7%). Median age at repair was 4 days (IQR 3–6) and 59.6% of all defects required patch repair. Median length of stay was 29 days (IQR 16.8–50.0). Median length of follow up was 49 months (IQR 17.8–95.3) with 25 patients followed for more than 12 years. Long-term outcomes included gastroesophageal reflux disease (42.0%), diaphragmatic hernia recurrence (10.9%), asthma (23.6%), neurodevelopmental delay (28.6%), attention deficit hyperactivity disorder (7.3%), autism (1.6%), chest wall deformity (15.5%), scoliosis (11.4%), and inguinal hernia (6.7%). ConclusionAs survival of patients with CDH improves, long-term care must be continuously studied and fine-tuned to ensure appropriate surveillance and optimization of long-term outcomes.

Анатомічні варіанти вродженої діафрагмальної кили, їх клінічне значення та можливості пренатальної диференціації

Purpose — to present verified typical anatomical variants of isolated congenital diaphragmatic hernia and clinical outcomes in newborns depending on the type of pathology, to compare with data of prenatal examination, and to assess feasibility of prenatal differentiation of congenital diaphragmatic hernia. Materials and methods. The data of operation protocols and autopsy results of newborn patients with isolated congenital diaphragmatic hernia for the period 2007–2020 were analyzed, and then compared with prenatal exam data and clinical outcomes. Data from different anatomical variants of congenital diaphragmatic hernia were analyzed using descriptive statistics methods. Results. Anatomical data were evaluated in 67 cases with the following typical variants: left-sided non-communicating defect (20.9%), left-sided communicating with herniation of intestine (19.4%), intestine and stomach (26,9%), intestine, stomach and liver (19.4%, 13/67), right- sided communicating with intestine and liver herniation (10.4%), right- sided non-communicating (1.5%), bilateral communicating defects (1.5%). Mortality at the stage of stabilization in these variants was 0%, 0%, 11.1%, 30.8%, 71.4%, 0% and 100%, postoperative mortality, respectively, 7.1%, 0%, 12.5%, 44.4%, 0%, 0% (excluding bilateral hernia), total mortality 7.1%, 0%, 22.2%, 61.5%, 71.4%, 0%, 100%. Comparison of lung indices in patients with left-sided hernias showed their similarity in groups with non-communicating defects and communicating with herniation of intestine. Significant differences were found in the groups with herniation of the intestine and stomach, and intestines, stomach and liver. The mean liver-to-lung ratio in right-sided communicating defects was 3.7±1.9, in left-sided communicating defects 1.7±0.8 and in non-communicating 0.44±0.25, the difference between all groups was highly significant. Patterns of stomach position in different variants of pathology were determined. Conclusions. Analysis of postnatally verified cases of diaphragmatic hernia showed marked anatomical variability. The highest mortality and the lowest rate of surgical correction registered was in communicating right-sided defects, and in communicating left-sided with simultaneous herniation of the intestine, stomach and liver. The best outcomes were found in non-communicating defects, or in communicating with herniation of intestine. Prenatal evaluation of stomach position may be the basis to differentiation between clinico-anatomical variants of the pathology. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the Institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interest was declared by the authors. Key words: congenital diaphragmatic hernia, congenital malformations, prenatal diagnosis.

Biomechanical comparison of titanium miniplates versus a variety of CAD/CAM plates in mandibular reconstruction

Titanium plate fixation of free flaps in mandibular reconstruction involves complications such as osseous non-union or imaging artefacts. Interosteotomy movement (IOM) is known to affect bone healing. This study aimed to compare IOM and mechanical integrity of four different fixation systems in a mandible reconstruction model. Two polyurethane (PU) fibula segments were fixed in right-sided defects of PU mandibles. Laser-melted patient-specific titanium plates were fixed with non-locking-screws (Ti-NL) or locking-screws (Ti-L). The third group consisted of locking-screws for patient-specific polyetheretherketone (PEEK-L) plates. The last group used titanium miniplates and monocortical screw fixation (Ti-MP). All models were loaded unilaterally via cyclic dynamic loading with increasing loads to simulate mastication. IOM was registered using a 3D optical tracking system. PEEK-L showed highest vertical displacement (p=0.010), lowest stiffness (p=0.004) and highest IOM (p=0.001). All specimen in PEEK-L demonstrated abnormal bending (n=5) or plate fracture (n=1). Vertical displacement or stiffness did not differ between any of Ti-MP, Ti-L and Ti-NL. IOM in Ti-MP was higher than in Ti-L and Ti-NL (p=0.001). Mechanical integrity of all titanium plates complies with established standards. In this model, the screw system did not influence IOM. In the tested composition and shape, PEEK plates do not seem to guarantee sufficient mechanical integrity for a use in mandibular reconstruction. Thus modifications are needed. Future clinical studies are needed to clarify optimal IOM after mandible reconstruction.

Tessier 4 right-sided orofacial cleft deformity with associated congenital limb anomalies − a case report and literature review

To report the case of a four year old girl with Tessier 4 right-sided orofacial cleft deformity, type I left cleft foot and hypoplastic right thumb. The patient presented with right-sided congenital orofacial defect, left foot defect and abnormally small right thumb noticed at birth. The pregnancy, labor and delivery periods were uneventful. She subsequently had repair of the orofacial cleft and the cleft foot defects. The post-operative period was uneventful. The patient is currently being followed up in the clinic. Tessier 4 cleft, though a rare orofacial cleft deformity may occasionally be associated with other congenital anomalies as it is found in the index case.

OSTEOINDUCTIVE POTENTIAL AND BONE HEALING CAPACITY OF NANOCRYSTALLINE HYDROXYAPATITE (nHA)VERSUS BIODENTINE OF SURGICALLY CREATED DEFECTS IN RABBITS’ ALVEOLAR PROCESS (AN ANIMAL STUDY)

Background: Bone defects resulting from trauma, tumor resection, infection, and congenital or acquired deformities remains an important clinical problem. Synthetic nano-crystalline hydroxyapatite, Nano bone, was successfully used in healing of bone defects without revealing negative side effects. Biodentine; a calcium-silicate based material was reported to have osteogenic and angiogenic properties.Objectives: This study aims to investigate the initial osteoinductive potential of Nano Bone and Biodentine on surgically created defects in rabbit’s alveolar process.Methods: 30 adult male rabbits (1-1.5kg) were used in this study. Bilateral bone defects were created in the mandibles of all rabbits, one in each side; the right sides were experimental, and the lefts were kept empty as control. Animals were then divided into two groups (15 rabbits each); Group I (Biodentine): The right-side defects were loaded with Biodentine material. Group II (Nano Bone): Nano Bone was packed in the right-side defects. Five rabbits were euthanized from each group at; 3, 7 and 14 days postoperatively. Bone defects’ specimens were prepared for histological examination by light microscope as well as quantitative analysis of gene expression of collagen1 alpha and Runx-2 by real time PCR.Results: Biodentine had initiated osteogenesis; yet the newly formed bone was apparently of lesser quality than that formed with Nano Bone. Runx- 2 showed significant increase in Nano Bone compared to Biodentine at 1 week, while collagen1 alpha gene expression was significantly increased at all intervals.Conclusion: Both Nano Bone and Biodentine had initiated osteogenesis. Nano bone showed better healing results when compared to Biodentine.

Preferential Associated Malformation in Patients With Anotia and Microtia

Few epidemiological studies have investigated the external ear malformations anotia and microtia. The authors' study aimed to investigate the relationships between age, sex, type of microtia, and birth place and associated malformation as seen in 1 private Japanese clinic. Cases of anotia/microtia that presented in Nagata Microtia and Reconstructive Plastic Surgery Clinic (Saitama, Japan) between 2005 and 2018 were included in the study. The authors identified 1896 patients with anotia/microtia with or without associated malformation. Most were primary cases, with some secondary reconstruction cases wherein the primary surgery was performed at another hospital. Cases were classified with Nagata classification; lobule type, small concha type, concha type, and anotia. Cryptotia was also observed in this study. Among the patients, 61.1% were male, 85.4% had unilateral defects (69.0% LB), and 59.1% had a right-sided defect. Most patients were less than 1 year old (15.0%) or 8 to 10 years old (5.5%-6.3%) on first examination, while 58% were from the Kanto region, including Tokyo. Regarding concomitant disorders, 32.7% had an accompanying malformation, while 13.3% had associated syndromes (eg, craniofacial microsomia, Treacher Collins syndrome). To conclude, in the authors' clinic, most cases of anotia/microtia were LB, unilateral, and seen in male patients. Information regarding several characteristic clinical features was obtained, especially that clefts and musculoskeletal deformities of the skull/face and jaw were the main accompanying malformations.

Adjunctive hyperbaric oxygen therapy for irradiated rat calvarial defects.

PurposeThe aim of this study was to conduct a histologic evaluation of irradiated calvarial defects in rats 4 weeks after applying fibroblast growth factor-2 (FGF-2) with hyaluronan or biphasic calcium phosphate (BCP) block in the presence or absence of adjunctive hyperbaric oxygen (HBO) therapy.MethodsTwenty rats were divided into HBO and non-HBO (NHBO) groups, each of which was divided into FGF-2 and BCP-block subgroups according to the grafted material. Localized radiation with a single 12-Gy dose was applied to the calvaria of rats to simulate radiotherapy. Four weeks after applying this radiation, 2 symmetrical circular defects with a diameter of 6 mm were created in the parietal bones of each animal. The right-side defect was filled with the materials mentioned above and the left-side defect was not filled (as a control). All defects were covered with a resorbable barrier membrane. During 4 weeks of healing, 1 hour of HBO therapy was applied to the rats in the HBO groups 5 times a week. The rats were then killed, and the calvarial specimens were harvested for radiographic and histologic analyses.ResultsNew bone formation was greatest in the FGF-2 subgroup, and improvement was not found in the BCP subgroup. HBO seemed to have a minimal effect on new bone formation. There was tendency for more angiogenesis in the HBO groups than the NHBO groups, but the group with HBO and FGF-2 did not show significantly better outcomes than the HBO-only group or the NHBO group with FGF-2.ConclusionsHBO exerted beneficial effects on angiogenesis in calvarial defects of irradiated rats over a 4-week healing period, but it appeared to have minimal effects on bone regeneration. FGF-2 seemed to enhance new bone formation and angiogenesis, but its efficacy appeared to be reduced when HBO was applied.

Effect of early negative fluid balance on the early postoperative recovery in children after surgical repair of congenital heart disease with enlarged right ventricle

Objective To estimate the effect of early fluid removal on the early postoperative recovery in children after surgical repair of congenital heart disease with enlarged right ventricle via a randomized trial. Methods One hundred and twenty patients with right-sided complex congenital heart defect who underwent cardiac surgery by cardiopulmonary bypass during January 2017 to June 2017 were enrolled and were divided into two groups, Group-E and Group-C, when the hemodynamics was stable within 3 hours after the surgery.Patients in Group-E were treated with early fluid removal, but Group-C remained conventional therapy.The data of the hemodynamics and outcomes were collected from the postoperative day to the 2nd day post-operation. Results Fluid removal therapy was started in Group-E at (4.39±0.85) h postoperatively vs(10.17±2.77) h in Group-C (P<0.05). Patients in Group-E showed lower extravascular lung water index (ELWI), lower fluid overload and lower NT-proBNP compared with patients in Group-C on the first day of post-operation(P<0.01). Also, the advantages remained in Group-E on the second day but the ELWI showed no remarkable difference.The rate of reintubation(P<0.05), the duration of mechanical ventilation and the length of ICU stay (P<0.01)were significantly reduced in Group-E. Conclusion In patients with right ventricle enlarged complex congenital heart defect who underwent cardiac surgery by cardiopulmonary bypass, utilizing early negative fluid balance when the hemodynamics are stable and the right ventricle is obviously enlarged could achieve negative fluid balance, get extubated and discharge from ICU earlier, also present lower extravascular lung water index, lower incidence of weaning-induced pulmonary edema and reintubation. Key words: Negative fluid balance; Right ventricle enlargement; Congenital heart disease; Cardiac surgery; Early recovery

Prenatally versus postnatally diagnosed congenital diaphragmatic hernia – Side, stage, and outcome

AimTo compare outcomes between prenatally and postnatally diagnosed CDH in a large multicenter database of prospectively collected data and evaluate factors associated with poorer outcome for prenatally diagnosed CDH. Material and MethodsWe used information from the multicenter, multinational CDH Study Group database on patients born between 2007 and 2015. We compared differences between prenatally and postnatally diagnosed CDH with respect to survival, side, size, ECMO needs, associated major cardiac malformations and liver position. Results3746 cases of CDH were entered in the registry between 2007 and 2015, with an overall survival of 71%. Of those, 68% had a prenatal diagnosis. Survival rates were significantly better in the postnatally diagnosed group, 83 vs 65%. There was a higher proportion of bigger defect sizes, C and D, in the prenatally diagnosed group, but the survival rates were similar when patients were stratified by defect size. The rate of ECMO utilization was higher overall in the prenatally diagnosed group, 33 vs 22%, but it was similar within similar defect sizes. Right-sided defects are more commonly missed at prenatal screening than left-sided CDH, 53 vs 35% (p < 0.0001). ConclusionsPrenatally diagnosed CDH is associated with larger defect sizes compared to those with a postnatal diagnosis, and consequently have higher morbidity and mortality. Right-sided CDH are more often missed at prenatal ultrasound. The increasing rate of prenatal detection requires a clear understanding of accurate risk stratification, in order to counsel families and to provide appropriate perinatal management. Level of EvidenceI for a Prognosis Study – This is a high-quality, prospective cohort study with 99% of patients followed to the study end point (death or discharge).

Is the Incidence of Gastroschisis Increasing Recently?

Aims and Objectives: Gastroschisis is a predominantly full thickness right-sided periumbilical abdominal wall defect. We have observed that the GS birth prevalence has more than doubled over the past few decades. The aim of our study is to point out the increasing incidence of the GS.Materials and Methods: We conducted a retrospective study to collect data of the GS, admitted in our institute during the period of 2 years from January 2015 to December 2016. The very high incidence of this congenital anomalies together with the fact that GS is the most common abdominal wall defect requiring neonatal operative intervention and its mortality rate is still very high that prompted us to study its demography, descriptive epidemiology, and quantifying mortality rate and try to analyze factors affecting outcome and cause that might explain this epidemiological pattern. Low- and middle-income countries are often reported to have a higher mortality when compared to patients born in the developed countries.Results: A total of 98 patients of the GS were admitted during the period of 2 years. The mortality and survival rate were 26.5% (26) and mortality 73.4% (72) respectively.Conclusion: Our data demonstrate that in our institution too, recent trends of increasing prevalence of GS are real. Still, we had a high mortality rate. This study highlights the need for further research to find out the causes of such high incidence rates and to improve our outcomes.

Laparoscopic transabdominal Morgagni hernia repair

Morgagni hernias are a rare finding in the adult population and represent 1%–3% of all congenital diaphragmatic hernias. Multiple approaches to these rare hernias have been described in the literature. Here, we present a novel technique of laparoscopic transabdominal repair using a combination of the Endo-Close device (Medtronic, Minneapolis, MN, USA) and the Ti-KNOT (LSI Solutions, Victor, NY, USA). In a patient with a large left anterior diaphragmatic defect, we performed transabdominal suturing utilizing the Endo-Close to perform primary closure of the defect, using the Ti-KNOT to secure the pledged sutures along the anterior fascia. Due to the size of the defect (7 cm × 10 cm), this primary repair was buttressed with polyester mesh. In a second patient with a smaller (6 cm × 8 cm) classic right-sided anterior diaphragmatic defect, we similarly performed laparoscopic transabdominal suturing using the Endo-Close to traverse both the anterior and posterior fascia and the Ti-KNOT to secure the sutures to perform a primary repair of the hernia. Both patients presented had an uneventful postoperative course and no indication of recurrence at 4 months. Morgagni hernias present unique technical challenges. In our experience, the combined use of transabdominal suture with laparoscopic knot placement device allowed for completion of both cases laparoscopically with minimal tension on the repairs.

Cerebral Hernia Caused By Epidural Hygroma Due to Excessive Drainage of Cerebrospinal Fluid: A Rare Case and Literature Review

The cerebral hernia is usually caused by intracranial hematoma, tumor, abscess. Here, we report a rare case of cerebral hernia caused by severe epidural hygroma. The patient was a 51-year-old male, with a large, right-sided skull defect and severe scalp depression, who had received a decompressive craniectomy for traumatic brain injury and a lumboperitoneal shunt for secondary hydrocephalus 6 months earlier. A cranioplasty with titanium mesh was performed after admitted. Unfortunately, he suffered from a complication of epidural fluid collection. Through repeated local treatment of the hygroma, the patient was not better but rather became more and more serious, and developed to cerebral hernia eventually. However, after finding out the root cause, the patient got dramatically improvement just by elevating the valve pressure of the lumboperitoneal shunt. The case and literature review are instructive to the treatment of patients with skull bone defect associated with hydrocephalus.

The influence of reading direction on hemianopic reading disorders

ABSTRACTHemianopic reading impairment is a consequence of a visual field defect to either the right or the left side and is characterized by an increased reading time and reduced reading performance. Depending on the side of the visual field defect, reading will be affected differently: Patients suffering from a visual field defect to the right side have noticeable difficulties in reading fluently with slowing. Patients suffering from a visual field defect to the left usually struggle to find the beginning of a line and read more fluently. It was suggested in the literature that changing the reading direction from horizontal to vertical may be a training strategy to reduce reading problems in patients with hemianopia. The aim of the study was to investigate the influence of reading direction on reading speed in patients with left- or right-sided visual field defects and in healthy controls. Method: In 13 patients with hemianopia and in 13 age-matched controls, reading speed was calculated for texts in standard as well as in clockwise rotated orientation of 90, 180, and 270°. Results: In both groups, text rotation reduced reading speed compared to standard reading. Patients with left-sided hemianopia had the greatest reduction after text rotation. Patients with right-sided hemianopia had the smallest speed reduction in 90° vertically rotated texts. Conclusions: Text rotation has different effects in left- or right-sided hemianopia patients. For patients with left-sided heminanopia, rotation of the text may not be a helpful training strategy, for right-sided hemianopia vertical rotation of the text of 90° may be a beneficial training strategy to reduce reading deficits.

Severe Congenital Diaphragmatic Hernia—Exemplary Management in Poland: Fetoscopic Endotracheal Occlusion

ABSTRACT Congenital diaphragmatic hernia (CDH) is a developmental closure defect resulting in discontinuity of the diaphragm. Abdominal viscera herniate into the chest leading to mediastinal shift and lung compression. Congenital diaphragmatic hernia occurs in approximately 1 in 4,000 live births. Vast majority of cases is on the left side of the diaphragm. Congenital diaphragmatic hernia is also associated with severe pulmonary hypoplasia and pulmonary arterial hypertension. Approximately 50 to 70% of cases of CDH are isolated, but may also be associated with rare and severe genetic syndromes. It is one of the most severe birth defects with extremely high neonatal mortality and morbidity. Prognosis is worse in cases of an abnormal chromosomal microarray, severe associated anomalies, right-sided defect, liver herniation, and lower fetal lung volume. In some countries, fetoscopic endotracheal occlusion (FETO) for severe CDH is offered to selected group of patients. Since 2014, this procedure is also available in Poland in the 1st Department of Obstetrics and Gynecology of Medical University of Warsaw. This article reviews management in diaphragmatic hernia and presents protocol implemented in our center. How to cite this article Wielgos M, Kosinski P. Severe Congenital Diaphragmatic Hernia—Exemplary Management in Poland: Fetoscopic Endotracheal Occlusion. Donald School J Ultrasound Obstet Gynecol 2016;10(2):178-179.

Right- versus left-sided congenital diaphragmatic hernia: a comparative outcomes analysis

PurposeRight-sided congenital diaphragmatic hernia (R-CDH) occurs in up to 25% of all CDH cases, but has been less widely studied compared to left-sided defects. We sought to compare characteristics and outcomes of left- versus right-sided defects in a large cohort of CDH patients who underwent standardized treatment and follow-up at a single institution. MethodsWe retrospectively reviewed charts of all CDH patients in our pulmonary hypoplasia program from January 2002 through December 2014. Categorical variables were analyzed by Fisher's exact test and continuous variables by Mann–Whitney t-test (p≤0.05). ResultsA total of 330 CDH patients were treated more than the 12-year study period, with 274 (83%) left-sided and 56 (17%) right-sided cases identified. Specific pulmonary morbidities were associated with R-CDH, with increased duration of nitric oxide therapy, increased requirement for tracheostomy, increased requirement for supplemental oxygen at the time of NICU discharge, and increased chronic pulmonary hypertension with requirement for long-term Sildenafil therapy. ConclusionsIn this series, R-CDH was not associated with increased mortality, but was associated with increased requirement for pulmonary vasodilatory therapy and requirement for tracheostomy. The high incidence of pulmonary complications indicates increased severity of pulmonary hypoplasia in R-CDH, supporting a role for delivery in tertiary centers with expertise in CDH management.

Bone regeneration in calvarial defects in a rat model by implantation of human bone marrow-derived mesenchymal stromal cell spheroids.

Mesenchymal stem cell (MSC) condensation contributes to membrane ossification by enhancing their osteodifferentiation. We investigated bone regeneration in rats using the human bone marrow-derived MSC-spheroids prepared by rotation culture, without synthetic or exogenous biomaterials. Bilateral calvarial defects (8 mm) were created in nude male rats; the left-sided defects were implanted with MSC-spheroids, β-tricalcium phosphate (β-TCP) granules, or β-TCP granules + MSC-spheroids, while the right-sided defects served as internal controls. Micro-computed tomography and immunohistochemical staining for osteocalcin/osteopontin indicated formation of new, full-thickness bones at the implantation sites, but not at the control sites in the MSC-spheroid group. Raman spectroscopy revealed similarity in the spectral properties of the repaired bone and native calvarial bone. Mechanical performance of the bones in the MSC-implanted group was good (50 and 60 % those of native bones, respectively). All tests showed poor bone regeneration in the β-TCP and β-TCP + MSC-spheroid groups. Thus, significant bone regeneration was achieved with MSC-spheroid implantation into bone defects, justifying further investigation.