Use of an app-based exercise therapy program including cognitive-behavioral techniques for the management of intermittent claudication.

OBJECTIVE: Clinical practice guidelines recommend supervised exercise therapy (SET) as first-line therapy for patients with peripheral artery disease (PAD) and intermittent claudication (IC). The Society for Vascular Surgery Appropriate Use Criteria for IC deems excercise therapy (ET) as appropriate for all patients with IC. However, compliance with recommendations for the use of ET is often poor owing to the lack of availability, patient travel requirements, and cost. Results of home-based ET programs have been mixed with a trend toward improved results with more frequent patient engagement. The feasibility, use, and effectiveness of a 12-week app-based structured ET program using cognitive-behavioral therapy (CBT) techniques for IC was evaluated. METHODS: Patients with PAD confirmed by an abnormal ankle-brachial index or toe-brachial index and IC were recruited prospectively to participate in Society for Vascular Surgery SET, a 12-week app-based ET program. Participants performed home 6-minute walk tests, completed quality-of-life surveys, received education options via micro learning courses (eg, What is PAD?, Exercise, and Nutrition), and ongoing health coaching using CBT techniques. They were instructed to record at least three 30-minute ET walks a week using their personal mobile phones. Programming also included daily doses of health education, coaching, and reminders sent via text message. RESULTS: One hundred thirty-nine patients (37% women; mean age, 65 years) were enrolled across 20 institutions (44% offered in-person ET programs). One hundred twenty patients (86%) completed the program. Participants recorded 201,163 minutes of walking 8,013,520 steps with the ET program, completing a total of 5049 SET walks. Nineteen enrolled participants (14%) became inactive because they either paused (14 participants: medical reasons, travel, or other) or withdrew (5 participants: security concerns, lack of motivation). Ninety-two percent of patients met their stated CBT specific, measurable, achievable, relevant, and time-bound goals. Freedom from intervention at 6 months was 92% and 69% at 12 months. CONCLUSIONS: Deployment of a 12-week app-based ET program for PAD incorporating CBT was feasible in achieving 86% program completion and effective at meeting guideline recommended activity goals. Ninety-two percent of participants achieved their CBT specific, measurable, achievable, relevant, and time-bound goals. The use of ET was increased by virtue of offering this program at institutions that did not offer ET.

Telemedicine platforms and their use in the coronavirus disease-19 era to deliver comprehensive vascular care.

Implementation of telemedicine for patient encounters optimizes personal safety and allows for continuity of patient care. Embracing telehealth reduces the use of personal protective equipment and other resources consumed during in-person visits. The use of telehealth has increased to historic levels in response to the coronavirus disease 2019 (COVID-19) pandemic. Telehealth may be a key modality to fight against COVID-19, allowing us to take care of patients, conserve personal protective equipment, and protect health care workers all while minimizing the risk of viral spread. We must not neglect vascular health issues while the coronavirus pandemic continues to flood many hospitals and keep people confined to their homes. Patients are not immune to diseases and illnesses such as stroke, critical limb ischemia, and deep vein thrombosis while being confined to their homes and afraid to visit hospitals. Emerging from the COVID-19 crisis, incorporating telemedicine into routine medical care is transformative. By leveraging digital technology, the authors discuss their experience with the implementation, workflow, coding, and reimbursement issues of telehealth during the COVID-19 era.

Septic Pulmonary Emboli From Peripheral Suppurative Thrombophlebitis: A Case Report and Literature Review.

BACKGROUND:: We report the case of a 90-year old woman who presented with septic pulmonary emboli due to suppurative thrombophlebitis at an old peripheral intravenous site. METHODS:: After unsuccessful treatment with antibiotics, the patient was taken to the operating room for excision and drainage of the purulent superficial vein. RESULTS:: We review the literature and discuss the presentation, risk factors, treatment options, and complications of this often-overlooked disease entity. CONCLUSIONS:: Suppurative thrombophlebitis is a rare but morbid disease that requires a high level of clinical suspicion to diagnose.

A Cross-Sectional Study of Prominent US Mobile Health Applications: Evaluating the Current Landscape.

Mobile health (mHealth) could offer unprecedented opportunity to provide medical support closer to the users. We have selected some relevant criteria to describe 100 apps from Google Play store and Apple's App Store's top suggestions in medical category. These characteristics were compared based on the paid or free nature of the apps, the target users: consumers or healthcare professionals, and the platform: Android or iOS. Seventeen provided functionalities and 27 medical subjects covered by these apps were also extracted. Our study shows that even in top rated mHealth apps, a high proportion lacks some basic criteria regarding the quality of the apps including the presence of a privacy policy, describing content sources, participation of the target users in the app development, etc. Paid apps did not ensure better quality compared to free apps. The current mHealth market is not mature enough to be used widely and recommended by healthcare professionals.

Utilizing Smartphone-Based Machine Learning in Medical Monitor Data Collection: Seven Segment Digit Recognition.

Biometric measurements captured from medical devices, such as blood pressure gauges, glucose monitors, and weighing scales, are essential to tracking a patient's health. Trends in these measurements can accurately track diabetes, cardiovascular issues, and assist medication management for patients. Currently, patients record their results and date of measurement in a physical notebook. It may be weeks before a doctor sees a patient's records and can assess the health of the patient. With a predicted 6.8 billion smartphones in the world by 20221, health monitoring platforms, such as Apple's HealthKit2, can be leveraged to provide the right care at the right time. This research presents a mobile application that enables users to capture medical monitor data and send it to their doctor swiftly. A key contribution of this paper is a robust engine that can recognize digits from medical monitors with an accuracy of 98.2%.

Use of a proactive duplex ultrasound protocol for hemodialysis access.

OBJECTIVE: Arteriovenous fistula (AVF) creation is the preferred approach for hemodialysis access; however, the maturation of AVFs is known to be poor. We established a proactive early duplex ultrasound (DUS) surveillance protocol for evaluating AVFs before attempted access. This study determined the effect of this protocol related to improving AVF maturation. METHODS: From 2008 to 2013, 153 patients received new upper extremity AVFs and an early DUS surveillance protocol at a single academic institution. The protocol involved an early DUS evaluation before hemodialysis cannulation of the AVF at 4 to 8 weeks after AVF creation. A positive DUS result was identified as a peak systolic velocity of >375 cm/s or a >50% stenosis on gray scale imaging, along with decreased velocity in the outflow vein. Patients with positive DUS findings underwent prophylactic endovascular or open intervention to assist with AVF maturation. Nature of secondary interventions, as well as AVF patency and maturation, were assessed. Overall clinical outcomes and fistula patency were investigated. RESULTS: During the study period, 183 upper extremity AVFs were created in 153 patients, including 82 radiocephalic, 63 brachiocephalic, and 38 brachiobasilic AVFs. A mortality rate of 43% (n = 66) was observed in a median follow-up period of 34.5 months (interquartile range, 19.6-46.9). A total of 164 early DUS were performed at a median of 6 weeks (interquartile range, 3.4-9.6 weeks) after the initial creation. Early DUS showed nine AVFs were occluded and were excluded from further analysis. Hemodynamically significant lesions were found in 62 AVFs (40%); however, only 17 (11%) were associated with an abnormal physical examination. Positive DUS finding prompted a secondary intervention in 81% of the patients. Among those with positive early DUS findings, AVF maturation was 70% in those undergoing a secondary intervention compared with 25% in those not undergoing a prophylactic intervention (P = .011). Primary-assisted patency for AVFs with early positive and negative DUS findings were 83% and 96% at 6 months, 64% and 89% at 1 year, and 52% and 82% at 2 years, respectively (P < .001). CONCLUSIONS: Early DUS surveillance of AVFs before initial access is reasonable to identify problematic AVFs that may not be reliably detected on clinical examination. Although DUS criteria for AVFs have yet to be universally accepted, proactive early postoperative DUS interrogation assists in the early detection of dysfunctional AVFs and improvement of fistula maturation. Despite improved patency in those with positive DUS findings who undergo prophylactic secondary intervention, overall patency remains inferior to those without an abnormality detected on early DUS imaging.

TElmisartan in the management of abDominal aortic aneurYsm (TEDY): The study protocol for a randomized controlled trial.

BACKGROUND: Experimental studies suggest that angiotensin II plays a central role in the pathogenesis of abdominal aortic aneurysm. This trial aims to evaluate the efficacy of the angiotensin receptor blocker telmisartan in limiting the progression of abdominal aortic aneurysm. METHODS/DESIGN: Telmisartan in the management of abdominal aortic aneurysm (TEDY) is a multicentre, parallel-design, randomised, double-blind, placebo-controlled trial with an intention-to-treat analysis. We aim to randomly assign 300 participants with small abdominal aortic aneurysm to either 40 mg of telmisartan or identical placebo and follow patients over 2 years. The primary endpoint will be abdominal aortic aneurysm growth as measured by 1) maximum infra-renal aortic volume on computed tomographic angiography, 2) maximum orthogonal diameter on computed tomographic angiography, and 3) maximum diameter on ultrasound. Secondary endpoints include change in resting brachial blood pressure, abdominal aortic aneurysm biomarker profile and health-related quality of life. TEDY is an international collaboration conducted from major vascular centres in Australia, the United States and the Netherlands. DISCUSSION: Currently, no medication has been convincingly demonstrated to limit abdominal aortic aneurysm progression. TEDY will examine the potential of a promising treatment strategy for patients with small abdominal aortic aneurysms. TRIAL REGISTRATION: Australian and Leiden study centres: Australian New Zealand Clinical Trials Registry ACTRN12611000931976 , registered on 30 August 2011; Stanford study centre: clinicaltrials.gov NCT01683084 , registered on 5 September 2012.

Regulation of reactive oxygen species by p53: implications for nitric oxide-mediated apoptosis.

Nitric oxide (NO) induces vascular smooth muscle cell (VSMC) apoptosis in part through activation of p53. Traditionally, p53 has been thought of as the gatekeeper, determining if a cell should undergo arrest and repair or apoptosis following exposure to DNA-damaging agents, depending on the severity of the damage. However, our laboratory previously demonstrated that NO induces apoptosis to a much greater extent in p53(-/-) compared with p53(+/+) VSMC. Increased reactive oxygen species (ROS) within VSMC has been shown to induce VSMC apoptosis, and recently it was found that the absence of, or lack of, functional p53 leads to increased ROS and oxidative stress within different cell types. This study investigated the differences in intracellular ROS levels between p53(-/-) and p53(+/+) VSMC and examined if these differences were responsible for the increased susceptibility to NO-induced apoptosis observed in p53(-/-) VSMC. We found that p53 actually protects VSMC from NO-induced apoptosis by increasing antioxidant protein expression [i.e., peroxiredoxin-3 (PRx-3)], thereby reducing ROS levels and cellular oxidative stress. We also observed that the NO-induced apoptosis in p53(-/-) VSMC was largely abrogated by pretreatment with catalase. Furthermore, when the antioxidant protein PRx-3 and its specific electron acceptor thioredoxin-2 were silenced within p53(+/+) VSMC with small-interfering RNA, not only did these cells exhibit greater ROS production, but they also exhibited increased NO-induced apoptosis similar to that observed in p53(-/-) VSMC. These findings suggest that ROS mediate NO-induced VSMC apoptosis and that p53 protects VSMC from NO-induced apoptosis by decreasing intracellular ROS. This research demonstrates that p53 has antioxidant functions in stressed cells and also suggests that p53 has antiapoptotic properties.

Citric acid-based elastomers provide a biocompatible interface for vascular grafts.

Prosthetic vascular bypass grafting is associated with poor long-term patency rates. Herein, we report on the mid-term performance of expanded polytetrafluoroethylene (ePTFE) vascular grafts modified with a citric acid-based biodegradable elastomer. Through a spin-shearing method, ePTFE grafts were modified by mechanically coating a layer of poly(1,8 octanediol citrate) (POC) onto the luminal nodes and fibrils of the ePTFE. Control and POC-ePTFE grafts were implanted into the porcine carotid artery circulation as end-to-side bypass grafts. Grafts were assessed by duplex ultrasonography, magnetic resonance angiography, and digital subtraction contrast angiography and were all found to be patent with no hemodynamically significant stenoses. At 4 weeks, POC-ePTFE grafts were found to be biocompatible and resulted in a similar extent of neointimal hyperplasia as well as leukocyte and monocyte/macrophage infiltration as control ePTFE grafts. Furthermore, POC supported endothelial cell growth. Lastly, scanning electron microscopy confirmed the presence of POC on the ePTFE grafts at 4 weeks. Thus, these data reveal that surface modification of blood-contacting surfaces with POC results in a biocompatible surface that does not induce any untoward effects or inflammation in the vasculature. These findings are important as they will serve as the foundation for the development of a drug-eluting vascular graft.

Beneficial effect of a short-acting NO donor for the prevention of neointimal hyperplasia.

Nitric oxide (NO)-based therapies effectively inhibit neointimal hyperplasia in animal models of arterial injury and bypass grafting, but are not available clinically. We created a simple, effective, locally applied NO-eluting therapy to prevent restenosis after vascular procedures. We investigated the efficacy of perivascular delivery of two distinctly different diazeniumdiolate NO donors, 1-[2-(carboxylato)pyrrolidin-1-yl]diazen-1-ium-1,2-diolate (PROLI/NO) (short half-life) and diazeniumdiolated poly(acrylonitrile) (PAN/NO) (long half-life), in powder or gel form (30% poloxamer 407), at inhibiting neointimal hyperplasia using the rat carotid artery injury model. Two weeks postinjury, all of the NO-eluting therapies successfully reduced neointimal hyperplasia. However, most dramatically, PROLI/NO powder reduced intimal area by 91.2% (p<0.05) versus injury alone. PROLI/NO powder was noted to reduce the medial area (40.2% vs injury alone, p<0.05), whereas other groups showed no such effect. Three days postinjury, each NO treatment group significantly reduced cellular proliferation. However, inflammatory markers revealed a distinct pattern: PAN/NO groups displayed increased leukocyte infiltration (p<0.05), whereas PROLI/NO groups displayed less macrophage infiltration (p<0.05). In conclusion, perivascular delivery of diazeniumdiolate NO donors in powder or gel form effectively inhibits neointimal hyperplasia. Application of short-acting PROLI/NO powder most effectively inhibited neointimal hyperplasia and inflammation and may represent a simple, clinically applicable NO-eluting therapy to prevent neointimal hyperplasia and restenosis after open vascular interventions.

A reproducible porcine ePTFE arterial bypass model for neointimal hyperplasia.

BACKGROUND: Late failure of prosthetic vascular bypass grafting using expanded polytetrafluoroethylene (ePTFE) is secondary to the development of neointimal hyperplasia, most commonly at the distal anastomosis. To develop therapies that can improve upon current prosthetic vascular bypass grafting, a large animal model of prosthetic bypass grafting that results in reproducible neointimal hyperplasia is necessary. METHODS: We performed bilateral end-to-side carotid artery bypasses with 6 mm ePTFE in a porcine model (n = 11). We studied graft patency using magnetic resonance angiography (MRA, 3 wk), duplex ultrasonography (4 wk), and digital-subtraction contrast angiography (4 wk). Animals were sacrificed at 4 wk and morphometric analysis was performed. RESULTS: Of the 11 animals that underwent surgery, one pig died from respiratory compromise; of the remaining 10, graft patency was 90% at 4 wk. Peak systolic and end diastolic velocities were established for this model using ultrasonography. MRA, ultrasonography, and angiography confirmed graft patency and were complimentary tools to evaluate the grafts. Development of neointimal hyperplasia was reproducible at 4 wk in both the proximal and distal anastomoses (2.5 to 3 mm(2)) of the ePTFE bypass grafts. CONCLUSION: We developed a reproducible porcine ePTFE carotid artery bypass model for studying neointimal hyperplasia. Not only does this model allow for the manipulation and evaluation of potential therapies, but patency and neointimal hyperplasia can be easily evaluated by traditional means, such as MRA, ultrasonography, and angiography. This preclinical model is ideal for evaluation of novel therapies in vivo designed to inhibit neointimal hyperplasia following arterial reconstruction with prosthetic bypass grafting.

Differential gene expression between juvenile and adult dura mater: a window into what genes play a role in the regeneration of membranous bone.

BACKGROUND: Although reossification of large calvarial defects is possible in children, adults lack this tissue engineering capacity. In this study, the authors compared the differences in gene expression between juvenile and adult dura mater using a mouse cDNA microarray with 42,000 unique elements. METHODS: Non-suture-associated parietal bone was harvested from 6-day-old and 60-day-old mice. The dura mater was carefully dissected from the calvarial disk and snap-frozen. RNA was extracted from pooled dura mater for microarray analysis. The 25 most differentially expressed genes were listed, as were selected bone-related genes. In addition, quantitative real-time reverse-transcriptase polymerase chain reaction confirmation of selected genes-BMP-2, BMP-4, and BMP-7; and osteopontin (OP), osteocalcin (OC), and FGFR-1-was performed. RESULTS: Juvenile dura mater expressed significantly greater amounts of BMP-2 and OP. Minimal difference in OC expression was observed between juvenile and adult dura mater. Extracellular matrix proteins (Col3a1, 5a1, 6a1, and fibronectin 1), osteoblast differentiation markers (Runx2/Cbfa1, Itm2a, and FGFR-1), and the growth factor Ptn were among other genes with greater expression in juvenile dura mater. Markers of osteoclasts (Acp5, MMP9, Ctsk) and the multiple candidate gene Ntrk2 were also expressed at higher levels in the juvenile dura mater. CONCLUSIONS: These findings suggest a more differentiated osteoprogenitor population to exist along with a greater presence of osteoclasts in the juvenile dura mater relative to adults. In addition to establishing a baseline difference in gene expression between juvenile and adult dura mater, new genes potentially critical to the regenerative potential of juvenile calvaria were identified.

Abdominal aortic aneurysm-repair devices.

Traditional open aneurysm repair is associated with significant perioperative morbidity. The development of abdominal aneurysm-repair devices has provided a minimally invasive alternative to open repairs. The field of aneurysm-repair devices is burgeoning since the approval of the first device in 1999. A clear perioperative survival advantage and lower perioperative morbidity has been reported by multiple studies. In addition to benefiting the normal risk aortic aneurysm patient, this new technology is making the repair of aneurysms in older patients with high operative risk factors possible. Modifications to devices are introduced rapidly to overcome anatomical limitations and to improve on device-related complications such as endoleaks and migration. Limited long-term outcomes are available for newer devices, and life-long surveillance is still recommended for all patients. Patient selection and preoperative planning are the cornerstones to successful endovascular repair of abdominal aortic aneurysms.

Differential transcriptional expression profiles of juvenile and adult calvarial bone.

BACKGROUND: It has widely been observed that young children are capable of reossifying large calvarial defects, while adults lack this endogenous tissue-engineering capacity. The ability of juvenile animals to regenerate calvarial defects has been investigated in multiple animal models, including mice. In this study, the authors used cDNA microarrays to investigate the expression of osteogenesis-associated genes upstream and downstream of Runx2 in juvenile and adult mouse calvaria. METHODS: Nonsuture-associated parietal bone discs were harvested from 6-day-old (n = 50) and 60-day-old (n = 35) male CD-1 mice. After separation of the underlying dura mater and overlying pericranium, the calvarial discs were snap-frozen and RNA was extracted from pooled samples of calvaria for microarray analysis. Genes analyzed included cytokines, receptors, and cell-surface and matrix proteins both upstream and downstream of Runx2. RESULTS: Genes associated with the Runx2 pathway had notably higher levels in the juvenile versus adult calvaria. All genes except for osteocalcin were expressed at least twofold higher in the juvenile calvaria. This pattern was validated with quantitative real-time polymerase chain reaction. In addition, mRNA for potent osteoinductive growth factors was present at higher levels in the juvenile compared with the adult calvaria. CONCLUSIONS: These findings reflect a genomic environment of active osteoblast differentiation and ossification in the juvenile calvaria compared with the adult "quiescent" calvarial tissue. These data suggest that a decreased osteogenic potential of adult calvarial osteoblasts may, in part, explain the inability of adult animals to heal calvarial defects.

Bone morphogenetic protein 2 and retinoic acid accelerate in vivo bone formation, osteoclast recruitment, and bone turnover.

Reconstruction of craniofacial defects presents a substantial biomedical burden, and requires complex surgery. Interestingly, children after age 2 years and adults are unable to heal large skull defects. This nonhealing paradigm provides an excellent model system for craniofacial skeletal tissueengineering strategies. Previous studies have documented the in vivo osteogenic potential of adipose-derived stromal (ADS) cells and bone marrow-derived stromal (BMS) cells. This study investigates the ability to accelerate in vivo osteogenesis on ex vivo recombinant human bone morphogenetic protein 2 (BMP-2) and retinoic acid stimulation. Mouse osteoblasts, ADS cells, and BMS cells were seeded onto apatite-coated PLGA scaffolds, stimulated with rhBMP-2 and retinoic acid ex vivo for 4 weeks, and subsequently implanted into critically sized (4 mm) calvarial defects. Samples were harvested after 2, 4, 8, and 12 weeks. Areas of complete bony bridging were noted as early as 2 weeks in vivo; however, osteoclasts were attracted to the scaffold as identified by calcitonin receptor staining and tartrate-resistant acid phosphatase activity staining. Although the optimal method of in vitro osteogenic priming for mesenchymal cells remains unknown, these results provide evidence that BMP-2 and retinoic acid stimulation of multipotent cells ex vivo can subsequently induce significant quantities of bone formation within a short time period in vivo.

Applications of a mouse model of calvarial healing: differences in regenerative abilities of juveniles and adults.

Young children are capable of healing large calvarial defects, whereas adults lack this endogenous osseous tissue-engineering capacity. Despite the important clinical implications, little is known about the molecular and cell biology underlying this differential ability. Traditionally, guinea pig, rabbit, and rat models have been used to study the orchestration of calvarial healing. To harness the research potential of knockout and transgenic mice, the authors developed a mouse model for calvarial healing. Nonsuture-associated parietal defects 3, 4, and 5 mm in diameter were made in both juvenile (6-day-old, n = 15) and adult (60-day-old, n = 15) mice. Calvariae were harvested after 8 weeks and analyzed radiographically and histologically. Percentage of healing was quantified using Scion Image software analysis of calvarial radiographs. A significant difference in the ability to heal calvarial defects was seen between 6-day-old and 60-day-old mice when 3-, 4-, or 5-mm defects were created. The authors' analysis revealed that juvenile mice healed a significantly greater percentage of their calvarial defects than adult mice (juvenile mean percentage of healing: 3-mm defects, 59 percent; 4-mm defects, 65 percent; 5-mm defects, 44 percent; adult mean percentage of healing: <5 percent in all groups; p < 0.05). All three defect sizes were found to be critical in the adult, whereas significant healing was seen regardless of the size of the defect in juvenile mice. The establishment of this model will facilitate further, detailed evaluation of the molecular biology underlying the different regenerative abilities of juvenile versus adult mice and enhance research into membranous bone induction by making available powerful tools such as knockout and transgenic animals.

Mechanisms of murine cranial suture patency mediated by a dominant negative transforming growth factor-beta receptor adenovirus.

Using a physiologic model of mouse cranial suture fusion, the authors' laboratory has previously demonstrated that transforming growth factor (TGF)-betas appear to be more abundantly expressed in the suture complex of the fusing posterior frontal compared with the patent sagittal suture. Furthermore, the authors have shown that by blocking TGF-beta signaling with a replication-deficient adenovirus encoding a defective, dominant negative type II TGF-beta receptor (AdDN-TbetaRII), posterior frontal suture fusion was inhibited. In this study, the authors attempt to further elucidate the role of TGF-beta in cranial suture fusion by investigating possible mechanisms of AdDN-TbetaRII-mediated cranial suture patency using both an established organ culture model and a novel in vitro co-culture system that recapitulates the in vivo anatomic dura mater/cranial suture relationship. In this article, the authors demonstrate that blocking TGF-beta signaling with the AdDN-TbetaRII construct led to inhibition of cellular proliferation in the suture mesenchyme and subjacent dura mater during the early period of predicted posterior frontal suture fusion. Interestingly, co-culture experiments revealed that transfecting osteoblasts with AdDN-TbetaRII led to alterations in the gene expression levels of two important bone-related molecules (Msx2 and osteopontin). Inhibiting TGF-beta signaling prevented time-dependent suppression of Msx2 and prevented induction of osteopontin, thereby retarding osteoblast differentiation. Furthermore, the authors demonstrated that the AdDN-TbetaRII construct was capable of blocking TGF-beta -mediated up-regulation of collagen IalphaI, an extracellular matrix molecule important for bone formation. Collectively, these data strongly suggest that AdDN-TbetaRII maintains posterior frontal patency, in part by altering early events in de novo bone formation, including cellular proliferation and early extracellular matrix production.

Adipose-derived adult stromal cells heal critical-size mouse calvarial defects.

In adults and children over two years of age, large cranial defects do not reossify successfully, posing a substantial biomedical burden. The osteogenic potential of bone marrow stromal (BMS) cells has been documented. This study investigates the in vivo osteogenic capability of adipose-derived adult stromal (ADAS) cells, BMS cells, calvarial-derived osteoblasts and dura mater cells to heal critical-size mouse calvarial defects. Implanted, apatite-coated, PLGA scaffolds seeded with ADAS or BMS cells produced significant intramembranous bone formation by 2 weeks and areas of complete bony bridging by 12 weeks as shown by X-ray analysis, histology and live micromolecular imaging. The contribution of implanted cells to new bone formation was 84-99% by chromosomal detection. These data show that ADAS cells heal critical-size skeletal defects without genetic manipulation or the addition of exogenous growth factors.