The lack of easily isolated autologous endothelial cell (EC) sources is one of the major challenges with vascular tissue engineering interventions. This article examines the isolation and expansion of late-outgrowth endothelial progenitor cells (EPCs) from 50-mL samples of peripheral blood drawn from patients with significant coronary artery disease (CAD) and healthy young adult volunteers. In cases in which late-outgrowth EPCs were successfully isolated, the cells were assayed in vitro for their expression of EC markers, proliferation potential and ability to endothelialize synthetic materials, form new blood vessels, and produce nitric oxide. Late-outgrowth EPCs from patients with CAD and healthy volunteers exhibited critical EC markers and morphological characteristics that were analogous to a control population of human aortic ECs. To our knowledge, this is the first study to examine the suitability of late-outgrowth EPCs from patients with CAD for autologous endothelialization applications.

Late outgrowth endothelial progenitor cells (EPCs) derived from the peripheral blood of patients with significant coronary artery disease were sodded into the lumens of small diameter expanded polytetrafluoroethylene (ePTFE) vascular grafts. Grafts (1 mm inner diameter) were denucleated and sodded either with native EPCs or with EPCs transfected with an adenoviral vector containing the gene for human thrombomodulin (EPC+AdTM). EPC+AdTM was shown to increase the in vitro rate of graft activated protein C (APC) production 4-fold over grafts sodded with untransfected EPCs (p<0.05). Unsodded control and EPC-sodded and EPC+AdTM-sodded grafts were implanted bilaterally into the femoral arteries of athymic rats for 7 or 28 days. Unsodded control grafts, both with and without denucleation treatment, each exhibited 7-day patency rates of 25%. Unsodded grafts showed extensive thrombosis and were not tested for patency over 28 days. In contrast, grafts sodded with untransfected EPCs or EPC+AdTM both had 7-day patency rates of 88-89% and 28-day patency rates of 75-88%. Intimal hyperplasia was observed near both the proximal and distal anastomoses in all sodded graft conditions but did not appear to be the primary occlusive failure event. This in vivo study suggests autologous EPCs derived from the peripheral blood of patients with coronary artery disease may improve the performance of synthetic vascular grafts, although no differences were observed between untransfected EPCs and TM transfected EPCs.

Current pharmaceutical therapies can reduce hip fractures by up to 50%, but compliance to treatment is low and therapies take up to 18 months to reduce risk. Thus, alternative or complementary approaches to reduce the risk of hip fracture are needed. The AGN1 local osteo‐enhancement procedure (LOEP) is one such alternative approach, as it is designed to locally replace bone lost due to osteoporosis and provide immediate biomechanical benefit. This in vitro study evaluated the initial biomechanical impact of this treatment on human cadaveric femurs. We obtained 45 pairs of cadaveric femurs from women aged 77.8 ± 8.8 years. One femur of each pair was treated, while the contralateral femur served as an untreated control. Treatment included debridement, irrigation/suction, and injection of a triphasic calcium‐based implant (AGN1). Mechanical testing of the femora was performed in a sideways fall configuration 24 h after treatment. Of the 45 pairs, 4 had normal, 16 osteopenic, and 25 osteoporotic BMD T‐scores. Altogether, treatment increased failure load on average by 20.5% ( p < 0.0001). In the subset of osteoporotic femurs, treatment increased failure load by 26% and work to failure by 45% ( p < 0.01 for both). Treatment did not significantly affect stiffness in any group. These findings provide evidence that local delivery of the triphasic calcium‐based implant in the proximal femur is technically feasible and provides immediate biomechanical benefit. Our results provide strong rationale for additional studies investigating the utility of this approach for reducing the risk of hip fracture. © 2019 The Authors. Journal of Orthopaedic Research ® Published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society.

Wound healing is an intricate process involving the interaction of cells and molecules, resulting in a complex series of events that change the morphology and characteristics of the wounded area. Interactive animations are useful for illustrating challenging concepts, helping students learn and retain new material. Instructional PowerPoint presentations describing the basic elements of cutaneous wound healing and the response of cutaneous tissue to sutures were developed by seven biomedical engineering students at Duke University. "Cutaneous Wound Healing.ppt" is an interactive presentation reviewing the four phases of wound healing (hemostasis, inflammation, repair, and remodeling) as well as the major molecular and cellular mechanisms that comprise these processes for cutaneous tissue. "Tissue Response to Sutures.ppt" is an interactive presentation that uses sutures to illustrate the foreign body response to biomaterials in cutaneous tissue. The tissue response program reviews the basics of suturing, common suture materials, and the tissue, cellular, and molecular responses to absorbable and nonabsorbable sutures. This manuscript provides a brief overview of the programs that are freely available on the Duke Center for Biomolecular and Tissue Engineering web site at http://bte.egr.duke.edu.

This first-inhuman study of AGN1 LOEP demonstrated that this minimally-invasive treatment durably increased aBMD in femurs of osteoporotic postmenopausal women. AGN1 resorption was coupled with new bone formation by 12 weeks and that new bone was maintained for at least 5-7 years resulting in substantially increased FEA-estimated femoral strength. Introduction This first-inhuman study evaluated feasibility, safety, and in vivo response to treating proximal femurs of postmenopausal osteoporotic women with a minimally-invasive local osteo-enhancement procedure (LOEP) to inject a resorbable triphasic osteoconductive implant material (AGN1). Methods This prospective cohort study enrolled 12 postmenopausal osteoporotic (femoral neck T-score ≤ − 2.5) women aged 56 to 89 years. AGN1 LOEP was performed on left femurs; right femurs were untreated controls. Subjects were followed-up for 5-7 years. Outcomes included adverse events, proximal femur areal bone mineral density (aBMD), AGN1 resorption, and replacement with bone by X-ray and CT, and finite element analysis (FEA) estimated hip strength. Results Baseline treated and control femoral neck aBMD was equivalent. Treated femoral neck aBMD increased by 68 ± 22%, 59 ± 24%, and 58 ± 27% over control at 12 and 24 weeks and 5-7 years, respectively (p < 0.001, all time points). Using conservative assumptions, FEA-estimated femoral strength increased by 41%, 37%, and 22% at 12 and 24 weeks and 5-7 years, respectively (p < 0.01, all time points). Qualitative analysis of X-ray and CT scans demonstrated that AGN1 resorption and replacement with bone was nearly complete by 24 weeks. By 5-7 years, AGN1 appeared to be fully resorbed and replaced with bone integrated with surrounding trabecular and cortical bone. No procedure-or device-related serious adverse events (SAEs) occurred. Conclusions Treating femurs of postmenopausal osteoporotic women with AGN1 LOEP results in a rapid, durable increase in aBMD and femoral strength. These results support the use and further clinical study of this approach in osteoporotic patients at high risk of hip fracture.