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Suliman S.,University of Bergen | Xing Z.,University of Bergen | Wu X.,Innsbruck Medical University | Xue Y.,University of Bergen | And 11 more authors.
Journal of Controlled Release | Year: 2015

A low dose of 1 μg rhBMP-2 was immobilised by four different functionalising techniques on recently developed poly(L-lactide)-co-(ε-caprolactone) [(poly(LLA-co-CL)] scaffolds. It was either (i) physisorbed on unmodified scaffolds [PHY], (ii) physisorbed onto scaffolds modified with nanodiamond particles [nDP-PHY], (iii) covalently linked onto nDPs thatwere used to modify the scaffolds [nDP-COV] or (iv) encapsulated in microspheres distributed on the scaffolds [MICS]. Release kinetics of BMP-2 fromthe different scaffolds was quantified using targeted mass spectrometry for up to 70 days. PHY scaffolds had an initial burst of release while MICS showed a gradual and sustained increase in release. In contrast, NDP-PHY and nDP-COV scaffolds showed no significant release, although nDP-PHY scaffolds maintained bioactivity of BMP-2. Human mesenchymal stem cells cultured in vitro showed upregulated BMP-2 and osteocalcin gene expression at both week 1 and week 3 in the MICS and nDP-PHY scaffold groups. These groups also demonstrated the highest BMP-2 extracellular protein levels as assessed by ELISA, and mineralization confirmed by Alizarin red. Cells grown on the PHY scaffolds in vitro expressed collagen type 1 alpha 2 early but the scaffold could not sustain rhBMP-2 release to express mineralization. After 4 weeks post-implantation using a rat mandible critical-sized defect model, micro-CT and Masson trichrome results showed accelerated bone regeneration in the PHY, nDP-PHY and MICS groups. The results demonstrate that PHY scaffolds may not be desirable for clinical use, since similar osteogenic potential was not seen under both in vitro and in vivo conditions, in contrast to nDP-PHY and MICS groups, where continuous low doses of BMP-2 induced satisfactory bone regeneration in both conditions. The nDP-PHY scaffolds used here in critical-sized bone defects for the first time appear to have promise compared to growth factors adsorbed onto a polymer alone and the short distance effect prevents adverse systemic side effects. © 2014 The Authors. Published by Elsevier B.V. Source


Steinke M.,Fraunhofer Project Group Regenerative Technologies in Oncology | Steinke M.,University of Wurzburg | Dally I.,University of Stuttgart | Friedel G.,Schillerhohe Hospital | And 3 more authors.
Tissue Engineering - Part A | Year: 2015

Different bioengineering techniques have been applied repeatedly for the reconstruction of extensive airway defects in the last few years. While short-term surgical success is evident, there is a lack of long-term results in patients. Here, we report the case of a young male who received a 5×2cm bioartificial airway patch for tracheoesophageal reconstruction focusing on clinical defect healing and histomorphological tissue reorganization 2.5 years after surgery. We generated bioartificial airway tissue using a cell-free biological vascularized scaffold that was re-endothelialized and reseeded with the recipient's autologous primary cells and we implanted it into the recipient's left main bronchus. To investigate host-integration 2.5 years after the implantation, we obtained biopsies of the implant and adjacent tracheal tissue and processed these for histological and immunohistochemical analyses. The early postoperative course was uneventful and the transplanted airway tissue was integrated into the host. 2.5 years after transplantation, a bronchoscopy confirmed the scar-free reconstruction of the former airway defect. Histological work-up documented respiratory airway mucosa lining the bronchial reconstruction, making it indistinguishable from native airway mucosa. After transplantation, our bioartificial airway tissue provided perfect airway healing, with no histological evidence of tissue dedifferentiation. © Mary Ann Liebert, Inc. 2015. Source


Fidler F.,Research Center Magnetic Resonance Bavaria | Steinke M.,Fraunhofer Project Group Regenerative Technologies in Oncology | Kraupner A.,nanoPET Pharma GmbH | Gruttner C.,Micromod GmbH | And 5 more authors.
IEEE Transactions on Magnetics | Year: 2015

In the field of regenerative medicine, we focus on repairing damaged tissue using appropriate cells for therapy that have healing capacities, such as human mesenchymal stem cells (hMSCs). Tissue healing using stem cells will only be possible if the cells can be homed to their target. Beside cell homing at the targeted organ, assessing the cell vitality is of paramount interest during the healing process. To guarantee cell homing, hMSCs have to be labeled for long-term, noninvasive cell monitoring. Cell homing of labeled cells with iron oxide nanoparticles can be tracked with various methods like magnetic particle imaging or magnetic resonance imaging. In this paper, we present our first results in monitoring the cell vitality in vitro based on magnetic particle spectroscopy findings. © 1965-2012 IEEE. Source


Steinke M.,Fraunhofer Project Group Regenerative Technologies in Oncology | Steinke M.,University of Wurzburg | Gross R.,University of Wurzburg | Walles H.,Fraunhofer Project Group Regenerative Technologies in Oncology | And 4 more authors.
Biomaterials | Year: 2014

To investigate interrelations of human obligate airway pathogens, such as Bordetella pertussis, and their hosts test systems with high invitro/invivo correlation are of urgent need. Using a tissue engineering approach, we generated a 3D test system of the airway mucosa with human tracheobronchial epithelial cells (hTEC) and fibroblasts seeded on a clinically implemented biological scaffold. To investigate if hTEC display tumour-specific characteristics we analysed Raman spectra of hTEC and the adenocarcinoma cell line Calu-3. To establish optimal conditions for infection studies, we treated human native airway mucosa segments with B.pertussis. Samples were processed for morphologic analysis. Whereas our test system consisting of differentiated epithelial cells and migrating fibroblasts shows high invitro/invivo correlation, hTEC seeded on the scaffold as monocultures did not resemble the invivo situation. Differences in Raman spectra of hTEC and Calu-3 were identified in distinct wave number ranges between 720 and 1662cm-1 indicating that hTEC do not display tumour-specific characteristics. Infection of native tissue with B.pertussis led to cytoplasmic vacuoles, damaged mitochondria and destroyed epithelial cells. Our test system is suitable for infection studies with human obligate airway pathogens by mimicking the physiological microenvironment of the human airway mucosa. © 2014 Elsevier Ltd. Source

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