Post-implantation Phase Research Articles

Human peri-gastruloids: a significant advancement in embryology research.

The peri-gastruloids comprise both embryonic (epiblast) and extraembryonic (hypoblast) tissues, faithfully mirroring crucial developmental events spanning from the immediate post-implantation phase to early organogenesis, encompassing the emergence of amniotic and yolk sac cavities, as well as the progression from bilaminar to trilaminar embryonic discs.

P146 PERIPHERALLY INSERTED CENTRAL VENOUS CATHETER AND PERSISTENT LEFT SUPERIOR VENA CAVA: WHAT SHOULD WE KNOW?

Abstract Peripherally inserted central catheters (PICCs) are widely used medical devices to provide medium to long–term infusion treatment and therapy. PICC placement is contraindicated in cases of deep–vein thrombosis, end–stage renal disease or if deep venous access is compromised. Among the possible complications there are some related to the interventional procedure (e.g. accidental puncture of an arterial vessel, injury to peripheral nerves, misplacement, arrhythmias, haematoma) and others related to the post–implantation phase (e.g. thrombosis, infection, gas emboli, phlebitis). One of the possible intra–procedural complications is the occasional finding of a persistent left superior vena cava (PLSVC). PLSVC is an anatomical variant present in at least 0.5% of the general population and its occurrence during interventional procedures is not uncommon. Clinical case description An 82–year–old woman was admitted to our Institute following a diagnosis of herpetic encephalitis (HSV1). She had a history of hypothyroidism undergoing substitution treatment. Cause the poor peripheral venous patrimony and the need of infusion therapy with acyclovir, levetiracetam and ceftriaxone, the indication for PICC implantation was given. After antibiotic prophylaxis and sterile field preparation, the procedure was performed with ultrasound–guided Seldinger technique by puncturing the left basilic vein. A successive X–ray showed the PICC running unusually parallel to the right sternum (Fig. 1). The echoscopy with bubble test allowed to visualize the agitated saline solution in the right atrium. In view of the suspected venous abnormality, the PICC was removed and a single–lumen MiniMidline 4F of 11 cm length was placed in the right basilic vein (4 mm). A subsequent chest CT scan visualised the PLSVC and its intrathoracic course, the presence of the right superior vena cava was also observed (Fig. 2). The PLSVC is an anatomical variant encountered during interventional procedures involving peripherally inserted central venous catheters. It is important to recognise this variant to avoid possible procedural and/or post–procedural related surgical complications.

Role of Uterine Telocytes During Pregnancy

Abstract Endometrial remolding and angiogenesis are critical events that occur during pregnancy in order to establish uteroplacental vascular communication. This study investigated the role of uterine telocytes (TCs) in pregnancy. We analyzed the distribution of TCs and morphological changes in the endometrium of the gravid rabbit uterus at different stages of pregnancy: after ovulation, pre-implantation (day 7), post-implantation (days 8 and 9), and mid-pregnancy (day 14) and late (days 21–28) pregnancy. TCs gradually increased with the progression of pregnancy. They had distinctive telopodes (TPs) and podoms, with intranucleolar chromatin. The TCs established contact with decidual cells, growing a glandular epithelium, blood vessels, and immune cells, such as lymphocytes, neutrophils, and macrophages. The TCs underwent morphological changes at the post-implantation phase. They acquired thick and voluminous TPs, formed an extensive three-dimensional (3D) labyrinth at mid-pregnancy, and exhibited irregular-shaped nuclei and a dilated rough endoplasmic reticulum at late pregnancy. They also acquired a convoluted contour-formed complex network. Scanning electron microscopy (SEM) showed an extensive 3D network in the endometrium, forming a condensed sheath at late pregnancy. Transmission electron microscopy and SEM detected fenestrated TPs, and TCs were identified by CD34 and vascular endothelial growth factor expression. TCs also expressed matrix metalloproteinase-9 and transforming growth factor beta-1. Results suggested that TCs might play an essential role in maternal placenta formation, especially decidualization, regulation of uterine gland development, and neovascularization of maternal uterine blood vessels.

Lipid Raft Facilitated Receptor Organization and Signaling: A Functional Rheostat in Embryonic Development, Stem Cell Biology and Cancer.

Molecular views of plasma membrane organization and dynamics are gradually changing over the past fifty years. Dynamics of plasma membrane instigate several signaling nexuses in eukaryotic cells. The striking feature of plasma membrane dynamics is that, it is internally transfigured into various subdomains of clustered macromolecules. Lipid rafts are nanoscale subdomains, enriched with cholesterol and sphingolipids, reside as floating entity mostly on the exoplasmic leaflet of the lipid bilayer. In terms of functionality, lipid rafts are unique among other membrane subdomains. Herein, advances on the roles of lipid rafts in cellular physiology and homeostasis are discussed, precisely, on how rafts dynamically harbor signaling proteins, including GPCRs, catalytic receptors, and ionotropic receptors within it and orchestrate multiple signaling pathways. In the developmental proceedings signaling are designed for patterning of overall organism and they differ from the somatic cell physiology and signaling of fully developed organisms. Some of the developmental signals are characteristic in maintenance of stemness and activated during several types of tumor development and cancer progression. The harmony between extracellular signaling and lineage specific transcriptional programs are extremely important for embryonic development. The roles of plasma membrane lipid rafts mediated signaling in lineage specificity, early embryonic development, stem cell maintenance are emerging. In view of this, we have highlighted and analyzed the roles of lipid rafts in receptor organization, cell signaling, and gene expression during embryonic development; from pre-implantation through the post-implantation phase, in stem cell and cancer biology.

GM-CSF perturbs cell identity in mouse pre-implantation embryos.

Growth factors became attractive candidates for medium supplementation to further improve the quality of embryo culture and to mimic in vivo nutrition. Granulocyte macrophage colony-stimulating factor (GM-CSF) is a cytokine influencing the maternal-fetal interface and supporting placental development in mouse and human. It is expressed in epithelial cells of the endometrium under the regulation of estrogens. The factor is already in clinical use and a large clinical trial showed that, if supplemented to an embryo culture medium, it leads to increased survival of embryos, especially in women with previous miscarriages. Animal and cell culture studies on isolated trophectoderm cells support an effect mainly on cellular expansion. Aim of this study was to investigate, if the supplementation of GM-CSF either in a human ART medium or in a mouse optimized medium, leads to a change in cell number and cell lineages in the early pre-implantation mouse embryo. Our data shows that mouse GM-CSF increased total cell numbers with increasing concentrations. This increase of cell number has not been found in embryos cultured in ART media with or without human GM-CSF (hGM-CSF) or in a mouse medium supplemented with different concentrations of hGM-CSF. The changes were caused by a marked difference in TE and primitive endoderm cell numbers but not due to a change in epiblast cell numbers. Additionally, results show an ectopic expression of NANOG among trophectoderm cells in both, human ART media (with and without GM-CSF) and at increasing concentrations in the mouse and the human GM-CSF supplemented media. In conclusion, we could show that GM-CSF has an effect on cell identity in mice, which might probably also occur in the human. Therefore, we would like to rare awareness that the use of supplements without proper research could bare risks for the embryo itself and probably also in the post-implantation phase.

Uterine Notch2 facilitates pregnancy recognition and corpus luteum maintenance via upregulating decidual Prl8a2.

The maternal recognition of pregnancy is a necessary prerequisite for gestation maintenance through prolonging the corpus luteum lifespan and ensuring progesterone production. In addition to pituitary prolactin and placental lactogens, decidual derived prolactin family members have been presumed to possess luteotropic effect. However, there was a lack of convincing evidence to support this hypothesis. Here, we unveiled an essential role of uterine Notch2 in pregnancy recognition and corpus luteum maintenance. Uterine-specific deletion of Notch2 did not affect female fertility. Nevertheless, the expression of decidual Prl8a2, a member of the prolactin family, was downregulated due to Notch2 ablation. Subsequently, we interrupted pituitary prolactin function to determine the luteotropic role of the decidua by employing the lipopolysaccharide-induced prolactin resistance model, or blocking the prolactin signaling by prolactin receptor-Fc fusion protein, or repressing pituitary prolactin release by dopamine receptor agonist bromocriptine, and found that Notch2-deficient females were more sensitive to these stresses and ended up in pregnancy loss resulting from abnormal corpus luteum function and insufficient serum progesterone level. Overexpression of Prl8a2 in Notch2 knockout mice rescued lipopolysaccharide-induced abortion, highlighting its luteotropic function. Further investigation adopting Rbpj knockout and DNMAML overexpression mouse models along with chromatin immunoprecipitation assay and luciferase analysis confirmed that Prl8a2 was regulated by the canonical Notch signaling. Collectively, our findings demonstrated that decidual prolactin members, under the control of uterine Notch signaling, assisted pituitary prolactin to sustain corpus luteum function and serum progesterone level during post-implantation phase, which was conducive to pregnancy recognition and maintenance.

A prospective, multicenter, international study to explore the effect of three different amplitude settings in female subjects with urinary urge incontinence receiving interstim therapy.

AimsThe aim of this study is to evaluate the effect of sub‐sensory amplitude settings of sacral neuromodulation therapy on overactive bladder symptoms in subjects with urinary urge incontinence.MethodsSubjects who qualified for a neurostimulator device implant were randomized to one of three amplitude settings (50% of sensory threshold [ST], 80% of ST, and ST). Subjects completed urinary voiding diaries (3‐day), International consultation on incontinence modular questionnaire—overactive bladder symptoms quality of life questionnaire, and patient global impression of improvement (PGI‐I) to assess change in voiding symptoms and quality of life (QoL) from baseline through 12 weeks.ResultsForty‐eight subjects had a successful test stimulation, 46 were implanted with a neurostimulator device and 43 completed the 12‐week follow‐up visit. The change from baseline to 12 weeks is −3.0 urinary incontinence (UI) episodes/day (95% confidence interval [CI]: −4.4 to −1.7) for the 50% of sensory threshold group, −2.9 UI episodes/day (95% CI: −4.7 to −1.2) for 80% of sensory threshold group, and −3.6 UI episodes/day (95% CI: −5.2 to −1.9) for the sensory threshold group. In each randomized group, improvements were observed in health‐related QoL, its subscales, and symptom interference. Subjects across all three randomization groups reported on the PGI‐I that their bladder condition was better at 12 weeks compared to before they were treated with InterStim therapy.ConclusionThese findings provide insights into possible advancements in the postimplantation phase of therapy with potential for improved patient comfort and increased device longevity.

Acute effects of adaptive Deep Brain Stimulation in Parkinson’s disease

BackgroundBeta-based adaptive Deep Brain Stimulation (aDBS) is effective in Parkinson’s disease (PD), when assessed in the immediate post-implantation phase. However, the potential benefits of aDBS in patients with electrodes chronically implanted, in whom changes due to the microlesion effect have disappeared, are yet to be assessed. MethodsTo determine the acute effectiveness and side-effect profile of aDBS in PD compared to conventional continuous DBS (cDBS) and no stimulation (NoStim), years after DBS implantation, 13 PD patients undergoing battery replacement were pseudo-randomised in a crossover fashion, into three conditions (NoStim, aDBS or cDBS), with a 2-min interval between them. Patient videos were blindly evaluated using a short version of the Unified Parkinson’s Disease Rating Scale (subUPDRS), and the Speech Intelligibility Test (SIT). ResultsMean disease duration was 16 years, and the mean time since DBS-implantation was 6.9 years. subUPDRS scores (11 patients tested) were significantly lower both in aDBS (p=<.001), and cDBS (p = .001), when compared to NoStim. Bradykinesia subscores were significantly lower in aDBS (p = .002), and did not achieve significance during cDBS (p = .08), when compared to NoStim. Two patients demonstrated re-emerging tremor during aDBS. SIT scores of patients who presented stimulation-induced dysarthria significantly worsened in cDBS (p = .009), but not in aDBS (p = .407), when compared to NoStim. Overall, stimulation was applied 48.8% of the time during aDBS. ConclusionBeta-based aDBS is effective in PD patients with bradykinetic phenotypes, delivers less stimulation than cDBS, and potentially has a more favourable speech side-effect profile. Patients with prominent tremor may require a modified adaptive strategy.

Human embryo: what about relatedness?

Many studies are still ongoing to allow a global comprehension of the complex mechanisms that characterize and regulate human embryo development during the first weeks of his life. In this article, we decided to explore in particular one aspect of human embryo development: relatedness. Using PubMed database, we selected articles related to this particular theme and 56 articles where included in our analysis. We considered three different types of relatedness: from embryo to mother, from mother to embryo and bilateral relatedness. For each article, we indicated what type of relatedness was mainly present either during pre-implantation phase or during implantation phase or during post-implantation phase. The complex interactions between the mother and the embryo have been discussed and represented using, as emerged from literature, a cooperative agents’ model.

Chronic Hemolysis Associated with Gastrointestinal Bleeding in Patients with Left Ventricular Assist Devices

Left ventricular assist devices (LVADs) are an increasingly prevalent form of mechanical support for patients with end-stage heart failure. LVAD-associated gastrointestinal bleeding (GIB) remains a common complication in this population with an incidence approaching 30%. Multiple mechanisms have been offered to explain this disproportionate rate of GIB. We hypothesize a novel mechanism by way of haptoglobin depletion secondary to chronic hemolysis. Haptoglobin has a key role in preserving Nitric Oxide (NO) signaling during hemolysis by binding cell-free hemoglobin. NO has been shown to maintain gastrointestinal endothelial integrity. We queried the electronic medical record at our institution for laboratory markers of hemolysis including undetectable haptoglobin in patients with LVADs in the post-implantation phase. We identified which patients with LVADs had GIB using QLIK. We used Fischer's exact test to look for association between undetectable haptoglobin and LVAD-associated GIB. This study included a total of 56 patients with LVADs. 45% (25/56) of patients had GIB and 55% (31/56) of patients did not have GIB. Of the subset of patients with GIB, 15 of 25 had undetectable haptoglobin levels. In the patients with no GIB, 9 of 31 had undetectable haptoglobin levels. The difference was statistically significant p=0.0296. In a single-institution sample of patient with LVADs, there is a statistically significant association between an undetectable haptoglobin post-LVAD implantation and GIB. This supports the hypothesis that chronic hemolysis may have a pathophysiologic role in LVAD-associated GIB. Cell-free hemoglobin, haptoglobin, and the NO pathway may each serve as therapeutic targets to reduce the morbidity and mortality of LVAD-associated GIB.

Can we See what we'll get: Sensed R Wave Amplitude Guided Programming of Implantable Cardiac Monitors

Background Injectable loop recorder (ILR) use has increased leading to increased follow-up burdens for many clinics. Programming variations by physician and sites also vary greatly, especially those of the Automatic Detection Events. Event rates tend to be higher in the immediate post-implantation phase due to acute healing at the insertion site. We analyzed one manufacturer (Confirm Rxtm, Abbott Laboratories) to determine if programming standards may help reduce event rates in this acute phase. Objective We compared Daily Auto-Detected Events (DADE) in patients with specified R-Wave amplitude based Programming (RWP) vs. Other Detection Programming (ODP) in the first 30 days post implant. Symptom initiated events were excluded for consistency between groups. Methods Patient DADE's were logged and reported by PaceMate (Sarasota, FL). Groups were divided into RWP (N=12) vs. ODP (N=20). Auto-recorded events were averaged in their respective groups to a create the DADE rate in which groups were compared for the first 30 days after implant. Results N=32 Patients were evaluated (age 63.7 +/-16.7). The mean DADEs in the RWP group was 1.98 +/-2.99 vs. 5.59 +/- 7.63 in the ODP group (P= N/S). In the ODP group, we compared RWP to out of box nominal setting and physician tailored programming showing DADE rates of 8.6+/-9.8 (P=0.038) vs. 3.06 +/-4.29 (P=N/S) respectively. Programming and analysis can be seen in table 1. Conclusion An overall 65% reduction in DADE's was seen with the RWA group vs. the ODP group. The nominal programming demonstrated he highest rate of DADE's.

Impella versus IABP in acute myocardial infarction complicated by cardiogenic shock

ObjectiveWe investigated the benefit of Impella, a modern percutaneous mechanical support (pMCS) device, versus former standard intra-aortic balloon pump (IABP) in acute myocardial infarction complicated by cardiogenic shock (AMICS).MethodsThis single-centre,...

Rat Whole Embryo Culture.

The direct effects of chemical exposures, environmental extremes, and nutrient quality/quantity have been very difficult to study in mammalian embryos due to their anatomical inaccessibility, paucity of tissue, and other factors that make human studies unethical. Many acute and chronic developmental anomalies can trace their origins to postimplantation phases of gestation, where the organs are first being established and growth and differentiation are in highly active states of flux. Most chemical insults and conditions that produce birth defects are believed to act during this period of organogenesis. The evolution of rodent whole embryo culture (WEC) techniques has provided a valuable experimental model where physiological conditions and exposures can be carefully controlled and manipulated to test hypotheses and explore biochemical and molecular mechanisms of action that would otherwise be extremely difficult. Exposure to chemicals can be controlled through their direct addition to the culture medium. Optimal in vitro culture conditions support the growth of intact, viable conceptuses (embryo and associated extraembryonic membranes) from early egg cylinder stages through the establishment of the neural plate, gastrulation, neural tube closure, onset of active heartbeat and circulation, and the initial formation of all major organ systems that occur prior to the establishment of a functional placenta. Detailed comparisons of in vivo and in vitro growth show that conceptuses grown in WEC are nearly identical, structurally and functionally, to conceptuses of the same developmental stage that are allowed to develop normally in utero during a comparable developmental period. Culture conditions and mechanical apparatuses can be modified to suit a large number of different experimental approaches and paradigms.

Complications in recipients of cardioverter-defibrillator or cardiac resynchronization therapy: Insights from Silesian Center Defibrillator registry.

Current real-life information from all-comers registries from middle and east Europe about the incidence and type of complications during long-term follow-up of patients with cardioverters-defibrillators (ICD) and cardiac resynchronization devices-defibrillators (CRT-D) is still insufficient. The aim of the study was to assess the incidence and determinants of short- and long-term complications related to implantable ICD and CRT-D. We studied 1,105 recipients hospitalized in our center in 2009-2013, followed for a mean of 2.4 years (total of 2,652 patient-years). The independent association between ICD and CRT-D recipients' and implantation-procedures' characteristics with the incidence of complications was analyzed using multivariable Cox regression analysis. In 2-month post-procedural period, 124 (11.2%) patients developed complications. Independent predictors of short-term complications (within 2 months) were: atrial fibrillation, dual chamber ICD implantation, and use of antiplatelet therapy or coumarin. Twenty-seven (2.44%) patients experienced complications, mostly lead-related (n = 21). Independent predictors of long-term complications (2-12 months after implantation) were atrial fibrillation and dual chamber ICD implantation. Despite significant technological progress and operators' experience, the occurrence of complications in ICD and CRT-D recipients is still substantial. Majority of complications are recorded in the early post-implantation phase. Analysis of independent predictors of complications seem to be essential in helping to reduce adverse events in the future and strongly supports the need for routine follow-up.

The Implantable Miniature Telescope as a Treatment Option for Individuals With End-Stage Age-Related Macular Degeneration

Abstract Date Presented 3/31/2017 The development of the Implantable Miniature Telescope provides a new treatment option for individuals with end-stage age-related macular degeneration to supplement the central vision of one eye. Occupational therapists play a key role in the pre- and postimplantation phases of the procedure. Primary Author and Speaker: Tara Boehne

96-49: Early and Long-term Complications in More Than One Thousand Recipients of Implantable Cardioverter-Defibrillator or Cardiac Resynchronization Therapy Defibrillators

Purpose: Today real-life information from all-comers registries about the type of complications and their incidence during long-term implantable cardioverters-defibrillators (ICD) and cardiac resynchronization devices – defibrillators (CRT-D) follow-up is still insufficient. The aim of the study was to assess the incidence and determinants of short and long-term complications related with ICD or CRT-D implantation. Methods: We studied 1105 ICD or CRT-D recipients included in Silesian Centre Defibrillator (SCD) registry in 2009-2013. The independent association of patient and implantation-procedure characteristics with the incidence of ICD/CRT-D complications was analyzed using multivariable Cox regression analysis. Summary: We analyzed population of 1105 patients, followed for a mean of 2.4 years, resulting in a total of 2652 patient-years. Within 2 months, 124 (11.2%) patients developed ICD/CRT-D complications. Independent predictors for short-term ones (occurring within 2 months) were atrial fibrillation, dual chamber ICD implantation and use of antiplatelet therapy or coumarin. Thereafter, 27 (2.44%) patients experienced complications, mostly lead-related (n =21). Independent predictors for long-term ICD/CRT-D complications were atrial fibrillation and dual chamber ICD implantation. Conclusions: Despite significant technological progress in ICD/CRT-D therapy, complication occurrence is still substantial. The most of complications are recorded in the early post-implantation phase. Analysis of complications type and frequency seem to be essential in helping to avoid of adverse events in the future and strongly supports the need of routinely performed follow-up.

Complexes of trophoblastic peptides and heat shock protein 70 as a novel contraceptive vaccine in a mouse model

The concept of contraceptive vaccines has interested reproductive biologists and immunologists for nearly 2 decades, but no approach has been approved. In this study, a new immunocontraceptive vaccine that targets placental trophoblasts was expored. We demonstrated that after in-vitro binding with heat shock protein 70, trophoblast-derived peptides can activate T cells both in vitro and in vivo. The activated T cells have a Th1 bias and specifically cause cytolysis of trophoblasts, leading to the termination of pregnancy. Such activated T cells seem to have an effect on early gestation, rather than influencing preimplantation. We did not observe side-effects of this vaccine in mice. In conclusion, a novel contraceptive strategy is described that uses heat shock protein 70-trophoblastic peptide complexes to generate a specific T-cell immune response against placental trophoblasts. This type of vaccine targeting the post-implantation phase does not generate a permanent effect but possibly raises an ethical issue.

Teratogenic effect of cadmium: From the developing embryo to the fetus

Cadmium is recognized as a toxic metal recognized by the United Nations Organization list, and also a potential teratogen in humans.&#x0D; Objective: Of this study was to review the teratogenic effects of Cd in the human embryonic development from pre implantation, implantation and post implantation, and impact on the placenta and fetus.&#x0D; Methodology: The levels of ingestion varies by country, being seafood and tobacco smoke the principal reported sources. This metal has a long half-life, ranging from 75 days to 26 years, and is associated in humans to many cancers.&#x0D; Results: The teratogenic impact of cadmium in each stage of the developing embryo is clear in animal models, but not in humans.&#x0D; Conclusions: In the pre-implantation phase it affects the progression from the two-cell stages to morula; in the implantation phase it affects the trophoblastic invasion; in post-implantation phase it affects organogenesis; in the placenta it decrease Zinc levels in the fetus.

Protocol for a randomized, placebo-controlled, double-blind clinical trial investigating sacral neuromodulation for neurogenic lower urinary tract dysfunction.

BackgroundSacral neuromodulation has become a well-established and widely accepted treatment for refractory non-neurogenic lower urinary tract dysfunction, but its value in patients with a neurological cause is unclear. Although there is evidence indicating that sacral neuromodulation may be effective and safe for treating neurogenic lower urinary tract dysfunction, the number of investigated patients is low and there is a lack of randomized controlled trials.Methods and designThis study is a prospective, randomized, placebo-controlled, double-blind multicenter trial including 4 sacral neuromodulation referral centers in Switzerland. Patients with refractory neurogenic lower urinary tract dysfunction are enrolled. After minimally invasive bilateral tined lead placement into the sacral foramina S3 and/or S4, patients undergo prolonged sacral neuromodulation testing for 3–6 weeks. In case of successful (defined as improvement of at least 50% in key bladder diary variables (i.e. number of voids and/or number of leakages, post void residual) compared to baseline values) prolonged sacral neuromodulation testing, the neuromodulator is implanted in the upper buttock. After a 2 months post-implantation phase when the neuromodulator is turned ON to optimize the effectiveness of neuromodulation using sub-sensory threshold stimulation, the patients are randomized in a 1:1 allocation in sacral neuromodulation ON or OFF. At the end of the 2 months double-blind sacral neuromodulation phase, the patients have a neuro-urological re-evaluation, unblinding takes place, and the neuromodulator is turned ON in all patients. The primary outcome measure is success of sacral neuromodulation, secondary outcome measures are adverse events, urodynamic parameters, questionnaires, and costs of sacral neuromodulation.DiscussionIt is of utmost importance to know whether the minimally invasive and completely reversible sacral neuromodulation would be a valuable treatment option for patients with refractory neurogenic lower urinary tract dysfunction. If this type of treatment is effective in the neurological population, it would revolutionize the management of neurogenic lower urinary tract dysfunction.Trial registrationTrial registration number:http://www.clinicaltrials.gov; Identifier: NCT02165774.

Implantation of Autologous Endothelial Progenitor Cells (EPCs) as a Conduit for Enhanced Vascularized Bone Regeneration

Effective bone graft regeneration requires rapid neovascularization of implanted grafts to ensure the survival of cells in the early post-implantation phase. Here, we investigated the incorporation of autologous endothelial progenitor cells (EPCs) for enhanced vascularization and bone regeneration in vivo.