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Jana Steger,1 Alissa Jell,1,2 Stefanie Ficht,3 Daniel Ostler,1 Markus Eblenkamp,3 Petra Mela,3 Dirk Wilhelm1,2 1Technical University of Munich, TUM School of Medicine, Chair of Research Group Minimally Invasive Interdisciplinary Therapeutical Intervention (MITI), Munich, Germany; 2Technical University of Munich, TUM School of Medicine, Clinic and Polyclinic for Surgery, Munich, Germany; 3Technical University of Munich, TUM School of Engineering and Design, Department of Mechanical Engineering and Munich Institute of Biomedical Engineering, Chair of Medical Materials and Implants, Garching, GermanyCorrespondence: Jana Steger, Tel +49 89 4140-5898, Email jana.steger@tum.dePurpose: Anastomosis creation after resective gastrointestinal surgery is a crucial task. The present review examines the techniques and implants currently available for anastomosis creation and analyses to which extent they already address our clinical needs, with a special focus on their potential to enable further trauma minimization in visceral surgery.Methods: A multi-database research was conducted in MEDLINE, Scopus, and Cochrane Library. Comparative controlled and uncontrolled clinical trials dealing with anastomosis creation techniques in the intestinal tract in both German and English were included and statistically significant differences in postoperative complication incidences were assessed using the RevMan5.4 Review Manager (Cochrane Collaboration, Oxford, UK).Results: All methods and implant types were analyzed and compared with respect to four dimensions, assessing the techniques’ current performances and further potentials for surgical trauma reduction. Postoperative outcome measures, such as leakage, stenosis, reoperation and mortality rates, as well as the tendency to cause bleeding, wound infections, abscesses, anastomotic hemorrhages, pulmonary embolisms, and fistulas were assessed, revealing the only statistically significant superiority of hand-suture over stapling anastomoses with respect to the occurrence of obstructions.Conclusion: Based on the overall complication rates, it is concluded that none of the anastomosis systems addresses the demands of operative trauma minimization sufficiently yet. Major problems are furthermore either low standardization potentials due to dependence on the surgeons’ levels of experience, high force application requirements for the actual anastomosis creation, or large and rigid device designs interfering with flexibility demands and size restrictions of the body’s natural access routes. There is still a need for innovative technologies, especially with regard to enabling incisionless interventions.Keywords: anastomotic technique, postoperative complications, ideal anastomosis, intraoperative trauma

Equipping medical devices with smart technologies holds great potential for the development of modern medical products. The development requires the identification of new integration strategies and the research of new material combinations due to the miniaturization of systems and increasing production figures. The realization of Smart Biomedical Devices requires a sufficient barrier effect (bioprotection) by appropriate encapsulation of the electronic components. Thinnest polymer coatings have proven to be suitable for conformal encapsulation. The aim of the study was to investigate the fundamental suitability of thin-film lacquers added with catalysts as coating materials for electronic systems with regard to their biological use. Due to long curing times of up to 14 days, eight different catalysts based on different chemical structures were added to the coating materials and their influence on a cytotoxic effect was investigated. A non-cytotoxic effect was observed for the organometallic catalysts based on tin, zirconium, titanium, bismuth, and tertiary amine. Most were resistant to steam sterilization. The curing time of the non-cytotoxic coatings could be significantly reduced by the addition of catalysts. The shortening of process times is an important economic aspect in the production of mass-produced Smart Biomedical Devices.

The design of Smart Biomedical Devices will be a defining element of future research in the context of intelligent medical devices for the Internet of Medical Things (IoMT). A prerequisite for serving the disposable market is the use of cost-effective electronic components and the highest reliability of the developed products in terms of biocompatibility and bioprotection. In the study, resistors, capacitors, and light-emitting diodes, different in their materials and construction forms, were examined. The selected types represented electronic components as they are commonly installed on electronic system from the segment of low-cost standard components. These were subjected to steam sterilization with up to 50 cycles, gamma sterilization, and a CCK-8 assay to test in vitro cytotoxicity. Functional failure could not be determined for any component. Gamma sterilization did not result in significant changes in resistance values, but in capacitors with barium titanate as dielectric. Non-cytotoxic electronic components could be identified. The results show that certain electronic standard components are suitable for disposable Smart Biomedical Devices.

Fibrin glue is a two-component adhesive used to stop bleeding, seal wound edges and for scaffolds in tissue engineering. Autologous products result in reduced risk of contamination and immunological responses compared to commercially available fibrin glue. However, reproducibility due to patient dependent sealant properties of autologous fibrin glue preparation is low. In this study a fully automated production process for both the fibrinogen and thrombin component from small blood volumes was developed. The resulting fibrinogen concentration, thrombin activity and sealant properties of the fibrin glue were determined. The fully automated and closed production system proved to be a promising tool for fast and easy production of autologous fibrin glue with an effective adhesive quality.

To overcome challenges for manufacturing of modern smart medical plastic parts by injection molding, e.g. for active implants, the optimization of the interface between electronics and the polymer component concerning adhesion and diffusion behavior is crucial. Our results indicate that a nano-sized SiOxCyHz layer formed by plasma-enhanced chemical vapour deposition (PE-CVD) via open air atmospheric pressure plasma jet (APPJ) and by use of a hexamthyldisiloxane (HMDSO) precursor can form a non-corrosive, anti-permeable and biocompatible coating. Due to the open air character of the APPJ process an inline coating before overmolding could be an easy applicable method and a promising advancement.

Open air atmospheric pressure plasma jet (APPJ) enhanced chemical vapour deposition process was used to deposit biocompatible SiOx/TiOx composite coatings. The as deposited films are hydrophilic and show visible light induced photocatalytic effect, which is a consequence of the formation of defects in the TiOx structure due to the plasma process. This photocatalytic effect was verified by the demonstration of an antimicrobial effect under visible light on E. coli as well as by degradation of Rhodamine B. The films are non-cytotoxic as shown by the cytocompatibility tests. The films are conductive to cell growth and are stable in DMEM and isopropanol. The structural evaluation using SEM, EDS and XPS shows a dispersion of TiOx phase in a SiOxCyHz matrix. These analyses were used to correlate the structure-property relationship of the composite coating.

Ensuring optimal climate conditions during cultivation is essential for successful and reproducible cell culture based investigation. Being the gold standard, carbon dioxide incubators fulfill this demand in various geometries and sizes to suit diverse cultivation applications. A door opening results in a climate breakdown followed by a restoration period during which optimal conditions cannot be guaranteed. The following paper investigates the influence of incubator door design to optimize climate retainment during the above mentioned event.

To establish photopolymers for the production of class II or class III medical products by additive manufacturing it is essential to know which components of photopolymeric systems, consisting of monomers, photoinitiators and additives, are the determining factors on their biocompatible properties. In this study the leachable substances of a cured photopolymeric system were eluted and identified by HPLC-MS detection. In addition the cured photopolymer was testes for cytotoxicity and genotoxicity according to DIN EN ISO 10993 for long time applications. The results showed that uncured residual monomers are the determining factor on the biocompatible properties of the photopolymeric system. Strategies to reduce these residual monomers in the cured photopolymer are presented.

Nasoalveolar moulding (NAM) has become a widely accepted and evidence-based treatment strategy for newborns with cleft lip and palate (CLP), attempting to reduce the cleft gap and to form an appropriately shaped alveolar arch by an intraoral patient-specific NAM plate and to erect the usually flattened nostrils towards a natural nose wing occurrence. The generation of such an appropriately shaped NAM plate requires, besides 3d information of the patient’s initially cleft lip and palate, an estimated target model of the maxilla. Previous studies showed the applicability of curve-based approaches to describe the maxilla during early infancy. We have developed an automated algorithm implemented with the programming language Python, describing the alveolar arch by an approximated ellipse. Therefore, the digitalized data sets of human maxillae were aligned to a global coordinate system with a total least square method and subsequently analyzed with the curvature-based algebraic point set surfaces (APSS) algorithm. The gathered information of height ratio and curvature allows the detection of points on the alveolar segments and therewith the fit of an ellipse describing the human maxilla. In 84.5% of 193 maxilla impressions of healthy newborns the fitted ellipses described the course of the maxilla within defined margins. Applying the algorithm to 38 newborns suffering from unilateral cleft lip and palate in 76.3% the fitted ellipses bridge the CLP alveolar segments, so that a harmonic alveolar arch can be deduced. Describing the alveolar arch by one or multiple ellipses allows (i) to automatically measure the dimensions of the maxilla, (ii) to derive a growth model during early infancy, (iii) to derive a healthy harmonic arch from CLP alveolar segments and (iv) to automatically generate a basic NAM device on the basis of the virtually modified maxilla.

Thrombocytes can be concentrated in blood derivatives and used as autologous transplants e.g. for wound treatment due to the release of growth factors such as platelet derived growth factor (PDGF). Conditions for processing and storage of these platelet-rich blood derivatives influence the release of PDGF from the platelet-bound α-granules into the plasma. In this study Platelet rich plasma (PRP) and Platelet concentrate (PC) were produced with a fully automated centrifugation system. Storage of PRP and PC for 1 h up to 4 months at temperatures between −20°C and +37°C was applied with the aim of evaluating the influence on the amount of released PDGF. Storage at −20°C resulted in the highest release of PDGF in PRP and a time dependency was determined: prolonged storage up to 1 month in PRP and 10 days in PC increased the release of PDGF. Regardless of the storage conditions, the release of PDGF per platelet was higher in PC than in PRP.

Abstract Background Duchenne Muscular Dystrophy is an inherited degenerative neuromuscular disease characterised by rapidly progressive muscle weakness. Currently, curative treatment is not available. Approaches for new treatments that improve muscle strength and quality of life depend on preclinical testing in animal models. The mdx mouse model is the most frequently used animal model for preclinical studies in muscular dystrophy research. Standardised pathology-relevant parameters of dystrophic muscle in mdx mice for histological analysis have been developed in international, collaborative efforts, but automation has not been accessible to most research groups. A standardised and mainly automated quantitative assessment of histopathological parameters in the mdx mouse model is desirable to allow an objective comparison between laboratories. Methods Immunological and histochemical reactions were used to obtain a double staining for fast and slow myosin. Additionally, fluorescence staining of the myofibre membranes allows defining the minimal Feret’s diameter. The staining of myonuclei with the fluorescence dye bisbenzimide H was utilised to identify nuclei located internally within myofibres. Relevant structures were extracted from the image as single objects and assigned to different object classes using web-based image analysis (MyoScan). Quantitative and morphometric data were analysed, e.g. the number of nuclei per fibre and minimal Feret’s diameter in 6 month old wild-type C57BL/10 mice and mdx mice. Results In the current version of the module “MyoScan”, essential parameters for histologic analysis of muscle sections were implemented including the minimal Feret’s diameter of the myofibres and the automated calculation of the percentage of internally nucleated myofibres. Morphometric data obtained in the present study were in good agreement with previously reported data in the literature and with data obtained from manual analysis. Conclusions A standardised and mainly automated quantitative assessment of histopathological parameters in the mdx mouse model is now available. Automated analysis of histological parameters is more rapid and less time-consuming. Moreover, results are unbiased and more reliable. Efficacy of therapeutic interventions, e.g. within the scope of a drug screening or therapeutic exon skipping, can be monitored. The automatic analysis system MyoScan used in this study is not limited exclusively to dystrophin-deficient mice but also represents a useful tool for applications in the research of other dystrophic pathologies, various other skeletal muscle diseases and degenerative neuromuscular disorders.

Purpose: The introduction of novel endoscopic instruments is essential to reduce trauma in visceral surgery. However, endoscopic device development is hampered by challenges in respecting the dimensional restrictions, due to the narrow access route, and by achieving adequate force transmission. As the overall goal of our research is the development of a patient adaptable, endoscopic anastomosis manipulator, biomechanical and size-related characterization of gastrointestinal organs are needed to determine technical requirements and thresholds to define functional design and load-compatible dimensioning of devices., Methods: We built an experimental setup to measure colon tissue compression piercing forces. We tested 54 parameter sets, including variations of three tissue fixation configurations, three piercing body configurations (four, eight, twelve spikes) and insertion trajectories of constant velocities (5 mms -1 , 10 mms -1 ,15 mms -1 ) and constant accelerations (5 mms -2 , 10 mms -2 , 15 mms -2 ) each in 5 samples. Furthermore, anatomical parameters (lumen diameter, tissue thickness) were recorded., Results: There was no statistically significant difference in insertion forces neither between the trajectory groups, nor for variation of tissue fixation configurations. However, we observed a statistically significant increase in insertion forces for increasing number of spikes. The maximum mean peak forces for four, eight and twelve spikes were 6.4 ± 1.5 N, 13.6 ± 1.4 N and 21.7 ± 5.8 N, respectively. The 5th percentile of specimen lumen diameters and pierced tissue thickness were 24.1 mm and 2.8 mm, and the 95th percentiles 40.1 mm and 4.8 mm, respectively., Conclusion: The setup enabled reliable biomechanical characterization of colon material, on the base of which design specifications for an endoscopic anastomosis device were derived. The axial implant closure unit must enable axial force transmission of at least 28 N (22 ± 6 N). Implant and applicator diameters must cover a range between 24 and 40 mm, and the implant gap, compressing anastomosed tissue, between 2 and 5 mm., (© 2021. The Author(s).)

Autologous platelet-rich blood derivatives are used in a variety of medical fields in which the enhancement of wound healing by applying growth factors released from platelets is an especially promising application. Treatment of the whole surface of large-area wounds with a small volume of blood derivatives is best achieved by spraying. In this study, we present a compact and self-contained spraying device without external connections such as a power supply or compressor. The biocompatible propellant R134a is used to aspirate and atomize the blood derivatives. A 3D-printed, two-substance nozzle functions as the operating unit, throttle, mixing zone and atomization unit. The spray characteristics were evaluated via experimental flow volume, cone and droplet size measurements. Biological evaluation was performed by flow cytometry comparing platelet activation in the blood derivatives before and after spraying, and PDGF ELISA comparing growth factor release, respectively. Homogeneity and morphology of the sprayed blood cells were evaluated with scanning electron microscopy. The results show that the developed spraying device has excellent spray characteristics with low mechanical impact on the cellular components of the blood derivatives. Our spraying device is a promising tool for applying evenly distributed platelet-rich blood derivatives to treatment sites., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Nasoalveolar molding (NAM) aims to improve nasal symmetry with a nasal stent in cleft lip and palate (CLP) patients. When plates have to be exchanged because of dentoalveolar growth or cleft reduction, the nasal stent has to be mounted onto a new plate. This procedure elongates visiting hours for patients and parents or requires second treatment sessions. This study introduces a quick-lock additive manufacturing solution for chairside nasal stent exchange called RapidNAM. A novel taping retention pin has been designed that enables nasal stent insertion. Patients with unilateral CLP were included in this study. Plaster models were digitalized and measured by two independent observers. Two methods of CAD/CAM-molding therapies were compared: (i) conventional adhesion of a nasal stent (CAD/CAM NAM); (ii) quick-lock system in which the nasal stent was transferred to another plate (RapidNAM). CAD/CAM NAM and its refinement RapidNAM significantly increased the cleft-side nasal height and tilted the nose towards symmetry. The quick-lock system minimizes wire adaptations, since the pre-existing stent can be reused. The new nasal stent development seems a feasible solution to minimize visiting hours but with clinically satisfactory results. This new nasal stent system combines traditional elements of NAM with CAD/CAM-technology.

Computer-aided design and computer-aided manufacturing (CAD/CAM) technology has been implemented in the treatment of cleft lip and palates (CLP) by several research groups. This pilot study presents a technique that combines intraoral molding with a semi-automated plate generation and 3D-printing. The clinical results of two intraoral molding approaches are compared. This is the first clinical investigation of semi-automated intraoral molding. Our study included newborns with unilateral CLP. Plaster models were digitalized and measured by two independent observers. Two methods of CAD/CAM-assisted intraoral molding were compared: (i) stepwise manual design of molding plates (conventional CAD/CAM-intraoral molding) and (ii) a semi-automated approach with an automated detection of alveolar ridges (called RapidNAM) assisted by a graphical user interface (GUI). Both approaches significantly narrowed the clefts and resulted in a harmonic alveolar crest alignment. The GUI was easy to use and generated intraoral molding devices within minutes. The presented design solution is an efficient technical refinement with good clinical results. The semi-automated plate generation with a feasible GUI is fast but allows individual adaptations. This promising technique might facilitate and foster the more widespread use of CAD/CAM-technology in intraoral molding therapy.

Microscale porous membranes are used in a wide range of technical and medical applications such as water treatment, dialysis and in vitro test systems. A promising approach to control membrane properties and overcome limitations of conventional fabrication techniques is given by additive manufacturing (AM). In this study, we designed and printed a microporous membrane via digital light processing and validated its use for biomedical in vitro applications based on the example of a cell culture insert. A multi-layer technique was developed, resulting in an eight-layer membrane with an average pore diameter of 25 µm. Image analyses proved the printing accuracy to be high with small deviations for an increasing number of layers. Permeability tests with brilliant blue FCF (E133, triarylmethane dye) and growth factors comparing the printed to track-etched membranes showed similar transfer dynamics and confirmed sufficient separation properties. Overall, the results showed that printing microporous polymer membranes is possible and highlight the potential of AM for biomedical in vitro applications such as cell culture inserts, scaffolds for tissue engineering or bioreactors.

This study describes the dentoalveolar and palatal growth during the first months of life. Knowledge concerning this development is essential to avoid unwanted events such as mucosal ulcerations or restriction of growth when cleft-lip and palate (CLP) patients are treated. The results involve the generation of CAD/CAM CLP-feeding plates. Intraoral impressions from 32 healthy newborns were taken monthly for 5 months, supplemented by measurements of body weight, length, and occipital-frontal head circumference. The casts were digitalized, and two observers manually selected defined anatomical landmarks on virtual 3-D models. The distances between these landmarks were evaluted. Statistical analysis included an inter-rater agreement analysis and the determination of growth. In total, 213 casts were analyzed, with 65 models excluded because of inaccuracies in impression-taking or cast production. Overall longitudinal growth was 20.3%, whereas transversal growth reached a maximum of 21.1%. Vertical growth was 32.4% at the tuberal level. On the basis of these results, a semiautomated series of feeding plates allowing for monthly expansion could be generated. The acquired data serve as a useful reference for other pediatric and orthofacial investigations and treatments. One such application is the automated, fully virtual manufacture of CLP-feeding plates based on only one impression-taking. Our data reveal when caution is needed to prevent ulceration. The series of plates generated can minimize the time-consuming impression-taking and the production of further plaster models. The method of measurement is suitable for documentary purposes. Clin. Anat. 30:846-854, 2017. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Nasoalveolar molding (NAM) is an accepted treatment strategy in presurgical cleft therapy. The major drawbacks of the treatment listed in the literature relate to the time of the treatment and the coordination of the required interdisciplinary team of therapists, parents, and patients. To overcome these limitations, we present the automated RapidNAM concept that facilitates the design and manufacturing process of NAM devices, and that allows the virtual modification and subsequent manufacture of the devices in advance, with a growth prediction factor adapted to the patient's natural growth. The RapidNAM concept involves (i) the prediction of three trajectories that envelope the fragmented alveolar segments with the goal to mimic a harmonic arch, (ii) the extrusion from the larger toward the smaller alveolar segment along the envelope curves toward the harmonic upper alveolar arch, and (iii) the generation of the NAM device with a ventilation hole, fixation pin, and fixation points for the nasal stents. A feasibility study for a vector-based approach was successfully conducted for unilateral and bilateral cleft lip and palate (CLP) patients. A comparison of the modified target models with the reference target models showed similar results. For further improvement, the number of landmarks used to modify the models was increased by a curve-based approach.

Purpose: X-ray fluoroscopy guidance is frequently used in medical interventions. Image-guided interventional procedures that employ localization for registration require accurate information about the C-arm's rotation angle that provides the data externally in real time. Optical, electromagnetic, and image-based pose tracking systems have limited convenience and accuracy. An alternative method to recover C-arm orientation was developed using an accelerometer as tilt sensor., Methods: The fluoroscopic C-arm's orientation was estimated using a tri-axial acceleration sensor mounted on the X-ray detector as a tilt sensor. When the C-arm is stationary, the measured acceleration direction corresponds to the gravitational force direction. The accelerometer was calibrated with respect to the C-arm's rotation along its two axes, using a high-accuracy optical tracker as a reference. The scaling and offset error of the sensor was compensated using polynomial fitting. The system was evaluated on a GE OEC 9800 C-arm. Results obtained by accelerometer, built-in sensor, and image-based tracking were compared, using optical tracking as ground truth data., Results: The accelerometer-based orientation measurement error for primary angle rotation was -0.1 ± 0.0° and for secondary angle rotation it was 0.1 ± 0.0°. The built-in sensor orientation measurement error for primary angle rotation was -0.1 ± 0.2°, and for secondary angle rotation it was 0.1 ± 0.2°. The image-based orientation measurement error for primary angle rotation was -0.1 ± 1.3°, and for secondary angle rotation it was -1.3 ± 0.3°., Conclusion: The accelerometer provided better results than the built-in sensor and image-based tracking. The accelerometer sensor is small, inexpensive, covers the full rotation range of the C-arm, does not require line of sight, and can be easily installed to any mobile X-ray machine. Therefore, accelerometer tilt sensing is a very promising applicant for orientation angle tracking of C-arm fluoroscopes.

Hydrogel-based biomaterial systems have great potential for tissue reconstruction by serving as temporary scaffolds and cell delivery vehicles for tissue engineering (TE). Hydrogels have poor mechanical properties and their rapid degradation limits the development and application of hydrogels in TE. In this study, nanofiber reinforced composite hydrogels were fabricated by incorporating electrospun poly(ε-caprolactone) (PCL)/gelatin 'blend' or 'coaxial' nanofibers into gelatin hydrogels. The morphological, mechanical, swelling and biodegradation properties of the nanocomposite hydrogels were evaluated and the results indicated that the moduli and compressive strengths of the nanofiber reinforced hydrogels were remarkably higher than those of pure gelatin hydrogels. By increasing the amount of incorporated nanofibers into the hydrogel, the Young's modulus of the composite hydrogels increased from 3.29 ± 1.02 kPa to 20.30 ± 1.79 kPa, while the strain at break decreased from 66.0 ± 1.1% to 52.0 ± 3.0%. Compared to composite hydrogels with coaxial nanofibers, those with blend nanofibers showed higher compressive strength and strain at break, but with lower modulus and energy dissipation properties. Biocompatibility evaluations of the nanofiber reinforced hydrogels were carried out using bone marrow mesenchymal stem cells (BM-MSCs) by cell proliferation assay and immunostaining analysis. The nanocomposite hydrogel with 25 mg ml(-1) PCL/gelatin 'blend' nanofibers (PGB25) was found to enhance cell proliferation, indicating that the 'nanocomposite hydrogels' might provide the necessary mechanical support and could be promising cell delivery systems for tissue regeneration.

After myocardial infarction, the implantation of stem cell seeded scaffolds on the ischemic zone represents a promising strategy for restoration of heart function. However, mechanical integrity and functionality of tissue engineered constructs need to be determined prior to implantation. Therefore, in this study a novel pulsatile bioreactor mimicking the myocardial contraction was developed to analyze the behavior of mesenchymal stem cells derived from umbilical cord tissue (UCMSC) colonized on titanium-coated polytetrafluorethylene scaffolds to friction stress. The design of the bioreactor enables a simple handling and defined mechanical forces on three seeded scaffolds at physiological conditions. The compact system made of acrylic glass, Teflon®, silicone, and stainless steel allows the comparison of different media, cells and scaffolds. The bioreactor can be gas sterilized and actuated in a standard incubator. Macroscopic observations and pressure-measurements showed a uniformly sinusoidal pulsation, indicating that the bioreactor performed well. Preliminary experiments to determine the adherence rate and morphology of UCMSC after mechanical loadings showed an almost confluent cellular coating without damage on the cell surface. In summary, the bioreactor is an adequate tool for the mechanical stress of seeded scaffolds and offers dynamic stimuli for pre-conditioning of cardiac tissue engineered constructs in vitro.

Umbilical cord tissue comprises an attractive new source for mesenchymal stem cells. Umbilical cord tissue-derived mesenchymal stem cells (UCMSC) exhibit self-renewal, multipotency and immunological naivity, and they can be obtained without medical intervention. The transfer of UCMSC to the ischemic region of the heart may have a favorable impact on tissue regeneration. Benefit from typical cell delivery by injection to the infarcted area is often limited due to poor cell retention and survival. Another route of administration is to use populated scaffolds implanted into the infarcted zone. In this paper, the seeding efficiency of UCMSC on uncoated and titanium-coated expanded polytetrafluoroethylene (ePTFE) scaffolds with different surface structures was determined. Dualmesh (DM) offers a corduroy-like surface in contrast to the comparatively planar surface of cardiovascular patch (CVP). The investigation of adherence, viability and proliferation of UCMSC demonstrates that titanium-coated scaffolds are superior to uncoated scaffolds, independent of the surface structure. Microscopic images reveal spherical UCMSC seeded on uncoated scaffolds. In contrast, UCMSC on titanium-coated scaffolds display their characteristic spindle-shaped morphology and a homogeneous coverage of CVP. In summary, titanium coating of clinically approved CVP enhances the retention of UCMSC and thus offers a potential cell delivery system for the repair of the damaged myocardium.

The aim of the present study was to develop methods for the rapid assessment of intimal quality of coronary bypass segments of venous origin, and to prevent endothelial damage by improved intraoperative handling of graft segments. Particular attention was paid to the influence of the composition of the preservation solution and the intravasal filling pressure on the degree of endothelialization. Intrava-sal exposure to Alcian blue at pH<3 resulted in highly specific staining of intimal regions with functionally or structurally damaged endothelium. Standardization of preparation, staining and image acquisition of the intimal surface of graft remnants and subsequent computer-aided planimetry of these images made it possible for the first time to perform rapid serial investigations for quality control of bypass grafts. Using saline as the rinsing and intraoperative storage medium resulted in the loss of more than 50% of the endothelium at intravasal pressures of 0-100 mmHg. Increasing the pressure resulted eventually in complete de-endothelialization. In contrast, grafts incubated in a customized plasma derivative tolerated pressures of up to 200 mmHg with no significant endothelial loss; and even after exposure to 1,000 mmHg (10 times the average mean arterial pressure!) more than 70% of the endothelium were intact and vital. These findings imply strongly that the quality of aortocoronary bypass grafts of venous origin can be improved substantially by the use of a plasma derivative solution for intraoperative preservation and by monitoring and controlling the intravasal pressures reached during sealing and storage.

In the present study we assessed the potential of human outgrowth endothelial cells (OEC), a subpopulation within endothelial progenitor cell cultures, to support the vascularization of a complex tissue engineered construct for bone. OEC cultured on starch polycaprolactone fiber meshes (SPCL) in monoculture retained their endothelial functionality and responded to angiogenic stimulation by VEGF (vascular endothelial growth factor) in fibrin gel-assays in vitro. Co-culture of OEC with human primary osteoblasts (pOB) on SPCL, induced an angiogenic activation of OEC towards microvessel-like structures achieved without additional supplementation with angiogenic growth factors. Effects of co-cultures with pOB on the vascularization process by OEC in vivo were tested by subcutaneous implantation of Matrigel plugs containing both, OEC and pOB, and resulted in OEC-derived blood vessels integrated into the host tissue and anastomosed to the vascular supply. In addition, morphometric analysis of the vascularization process by OEC indicated a better performance of OEC in the co-cultures with primary osteoblasts compared to monocultures of OEC. The contribution of OEC to vascular structures and the beneficial effect of the co-culture with primary human osteoblasts on the vascularization in vivo was additionally proven by subcutaneous implantation of pre-cellularized and pre-cultured SPCL constructs. OEC contributed to the vascular structures, by generating autogenic vessels or by incorporation into chimeric vessels consisting of both, human and mouse endothelial cells. The current data highlight the vasculogenic potential of OEC for bone tissue engineering applications and indicate a beneficial influence of constructs including both osteoblasts and endothelial cells for vascularization strategies.

Adult stem cells from umbilical cord and cord blood are an interesting alternative to embryonic stem cells because such research is commonly recognized as ethical undisputed and many aspects are still insufficiently investigated. In the context of the STEMMAT research project (STEM = Stem Cell and MAT = Material) different aspects of stem cells from umbilical cord and cord blood are investigated, to improve basic science understanding and potentially leading someday to a clinical application.

Postnatal stem cells play a decisive role in cell-based therapies due to their high proliferation activity and functional plasticity. On the one hand, basic research in cell biological processes of adult stem cells is crucial in order to establish them as therapeutic tools. On the other hand, development and enhancements of appropriate techniques are required: we need to establish defined technologies for extraction and differentiation of stem cells and to develop adequate cell carrier devices, scaffolds, and bioreactors for in vitro purposes. Furthermore, it is an interdisciplinary challenge to consider logistical aspects concerning isolation, transport, and storage of stem cells in order to use them in a wide range of activities in regenerative medicine. In this review we present the current methods of work and research on adult stem cells. We explain their therapeutic use and define requirements for future technological developments for work with postnatal stem cells.