1.
Intracoronary delivery of injectable bioabsorbable scaffold (IK-5001) to treat left ventricular remodeling after ST-elevation myocardial infarction: a first-in-man study.
Frey, N, Linke, A, Süselbeck, T, Müller-Ehmsen, J, Vermeersch, P, Schoors, D, Rosenberg, M, Bea, F, Tuvia, S, Leor, J
Circulation. Cardiovascular interventions. 2014;(6):806-12
Abstract
BACKGROUND We aimed to test, for the first time, the feasibility of intracoronary delivery of an innovative, injectable bioabsorbable scaffold (IK-5001), to prevent or reverse adverse left ventricular remodeling and dysfunction in patients after ST-segment-elevation myocardial infarction. METHODS AND RESULTS Patients (n=27) with moderate-to-large ST-segment-elevation myocardial infarctions, after successful revascularization, were enrolled. Two milliliters of IK-5001, a solution of 1% sodium alginate plus 0.3% calcium gluconate, was administered by selective injection through the infarct-related coronary artery within 7 days after myocardial infarction. IK-5001 is assumed to permeate the infarcted tissue, cross-linking into a hydrogel and forming a bioabsorbable cardiac scaffold. Coronary angiography, 3 minutes after injection, confirmed that the injection did not impair coronary flow and myocardial perfusion. Furthermore, IK-5001 deployment was not associated with additional myocardial injury or re-elevation of cardiac biomarkers. Clinical assessments, echocardiographic studies, 12-lead electrocardiograms, 24-hour Holter monitoring, blood tests, and completion of Minnesota Living with Heart Failure Questionnaires were repeated during follow-up visits at 30, 90, and 180 days after treatment. During a 6-month follow-up, these tests confirmed favorable tolerability of the procedure, without device-related adverse events, serious arrhythmias, blood test abnormalities, or death. Serial echocardiographic studies showed preservation of left ventricular indices and left ventricular ejection fraction. CONCLUSIONS This first-in-man pilot study shows that intracoronary deployment of an IK-5001 scaffold is feasible and well tolerated. Our results have promoted the initiation of a multicenter, randomized controlled trial to confirm the safety and efficacy of this new approach in high-risk patients after ST-segment-elevation myocardial infarction. CLINICAL TRIAL REGISTRATION URL http://www.clinicaltrials.gov. Unique identifier: NCT01226563.
2.
Non-destructive analysis of extracellular matrix development in cardiovascular tissue-engineered constructs.
Tuemen, M, Nguyen, DV, Raffius, J, Flanagan, TC, Dietrich, M, Frese, J, Schmitz-Rode, T, Jockenhoevel, S
Annals of biomedical engineering. 2013;(5):883-93
Abstract
In the field of tissue engineering, there is an increasing demand for non-destructive methods to quantify the synthesis of extracellular matrix (ECM) components such as collagens, elastin or sulphated glycosaminoglycans (sGAGs) in vitro as a quality control before clinical use. In this study, procollagen I carboxyterminal peptide (PICP), procollagen III aminoterminal peptide (PIIINP), tropoelastin and sGAGs are investigated for their potential use as non-destructive markers in culture medium of statically cultivated cell-seeded fibrin gels. Measurement of PICP as marker for type I collagen synthesis, and PIIINP as marker of type III collagen turnover, correlated well with the hydroxyproline content of the fibrin gels, with a Pearson correlation coefficient of 0.98 and 0.97, respectively. The measurement of tropoelastin as marker of elastin synthesis correlated with the amount of elastin retained in fibrin gels with a Pearson correlation coefficient of 0.99. sGAGs were retained in fibrin gels, but were not detectable in culture medium at any time of measurement. In conclusion, this study demonstrates the potential of PICP and tropoelastin as non-destructive culture medium markers for collagen and elastin synthesis. To our knowledge, this is the first study in cardiovascular tissue engineering investigating the whole of here proposed biomarkers of ECM synthesis to monitor the maturation process of developing tissue non-invasively, but for comprehensive assessment of ECM development, these biomarkers need to be investigated in further studies, employing dynamic cultivation conditions and more complex tissue constructs.
3.
Cranioplasty with adipose-derived stem cells and biomaterial: a novel method for cranial reconstruction.
Thesleff, T, Lehtimäki, K, Niskakangas, T, Mannerström, B, Miettinen, S, Suuronen, R, Öhman, J
Neurosurgery. 2011;(6):1535-40
Abstract
BACKGROUND There is no optimal method for reconstruction of large calvarial defects. Because of the limitations of autologous bone grafts and alloplastic materials, new methods for performing cranioplasties are needed. OBJECTIVE To create autologous bone to repair cranial defects. METHODS We performed a cranioplasty procedure with this new method in 4 patients who had large calvarial defects of different etiologies. We used autologous adipose-derived stem cells seeded in beta-tricalcium phosphate granules. For 2 patients, we used a bilaminate technique with resorbable mesh. RESULTS During follow-up, there were no clinically relevant postoperative complications. The computed tomography scans revealed satisfactory outcome in ossification, and in the clinical examinations, the outcomes were good. The cranioplasty was measured in Hounsfield units from each computed tomography scan. The Hounsfield units increased gradually to equal the value of bone. CONCLUSION The combination of scaffold material such as beta-tricalcium phosphate and autologous adipose-derived stem cells constitutes a promising model for reconstruction of human large cranial defects. The success of these clinical cases paves way for further studies and clinical applications to turn this method into a reliable treatment regimen.
4.
Tissue-engineered bone for maxillary sinus augmentation.
Schimming, R, Schmelzeisen, R
Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons. 2004;(6):724-9
Abstract
PURPOSE Autologous, allogenic, and alloplastic materials for bony reconstruction in the craniomaxillofacial region have specific drawbacks stimulating the ongoing search for new materials. Cultivated skin and mucosa grafts are in clinical routine use in head and neck reconstruction but so far, to the best of our knowledge, no successful clinical application has been described of periosteum-derived tissue-engineered bone for augmentation of the edentulous posterior maxilla. PATIENTS AND METHODS In a clinical study, augmentation of the posterior maxilla was carried out using a bone matrix derived from mandibular periosteum cells on an Ethisorb (Ethicon, Norderstedt, Germany) fleece. In this report, we show the fabrication of the matrix, clinical application, and results in 27 patients. RESULTS In 18 patients, an excellent clinical, radiologic, and histologic result could be proved 3 months after augmentation. Histologically, the bone biopsy samples from these patients revealed mineralized trabecular bone with remnants of the biomaterial. An unsuccessful result was found in 8 cases with a more extended augmentation procedure. The clinical inspection 3 months after augmentation showed almost no formation of new bone. In contrast, a replacement resorption with connective tissue was found. This may be the result of failure of the initial supply of the cells embedded within large cell-polymer constructs with sufficient oxygen and nutrients to sustain their survival and proliferation and allow for the integration of the developing tissue within the surrounding tissue. CONCLUSION Our achieved results suggest that periosteum-derived osteoblasts on a suitable matrix can form lamellar bone within 3 months after transplantation and provide a reliable basis for simultaneous or secondary insertion of dental implants.