TransTissue Technologies GmbH

Berlin, Germany

TransTissue Technologies GmbH

Berlin, Germany
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Kulawig R.,TransTissue Technologies GmbH | Kruger J.P.,TransTissue Technologies GmbH | Klein O.,Charité - Medical University of Berlin | Konthur Z.,Max Planck Institute for Molecular Genetics | And 4 more authors.
International Journal of Biochemistry and Cell Biology | Year: 2013

Human serum has the potential for mesenchymal progenitor cell recruitment in repair of articular cartilage lesions. It is unclear which factor(s) in serum mediate this migratory effect. Our goal was to identify cell recruiting factors in human serum fractions obtained by ion exchange chromatography. The recruiting activity of serum fractions on human subchondral mesenchymal progenitor cells was analyzed using 96-well chemotaxis assays. Protein composition of recruiting serum fractions were analyzed by mass spectrometry and showed 58 potential candidates. Fibronectin, gelsolin, lumican, thrombospondin-1 and WNT-9a were identified as key candidates for progenitor cell recruitment. Only human plasma derived and recombinant fibronectin showed significant recruiting activity on progenitors reaching 50-90% of the recruiting activity of normal human serum. Presence of fibronectin in all human serum fractions with recruiting activity was verified by Western blot analysis. This study shows that fibronectin is a key factor in human serum to recruit mesenchymal progenitor cells and might be involved in subchondral mesenchymal progenitor cell migration into cartilage defects after microfracture. © 2013 Elsevier Ltd.


Kreuz P.C.,University of Rostock | Muller S.,Albert Ludwigs University of Freiburg | Freymann U.,TransTissue Technologies GmbH | Erggelet C.,Albert Ludwigs University of Freiburg | And 3 more authors.
American Journal of Sports Medicine | Year: 2011

Background: Scaffold-assisted autologous chondrocyte implantation is a clinically effective procedure for cartilage repair, but biomechanical evaluations are still missing. Purpose: This study was conducted to assess the clinical efficacy, including biomechanical analyses, of BioSeed-C treatment for traumatic and degenerative cartilage defects of the knee. Study Design: Case series; Level of evidence, 4. Methods: The authors evaluated the midterm clinical and biomechanical outcome of BioSeed-C, a cell-based fibrin-polymer graft for the treatment of cartilage defects. Clinical outcome at 4-year follow-up was assessed in 52 patients with full-thickness cartilage defects, International Cartilage Repair Society (ICRS) stage III and IV. Clinical scoring was performed preoperatively and 48 months after implantation using the Lysholm score, the International Knee Documentation Committee (IKDC) score, the ICRS score, the Knee injury and Osteoarthritis Outcome Score (KOOS), and the Noyes score. Cartilage regeneration was assessed by magnetic resonance imaging (MRI) using the Henderson-Kreuz score. Biomechanical evaluation was performed by isokinetic strength measurements, comparing healthy and operated knee of each patient. Results: Clinical evaluation showed significant improvement in the Lysholm (from 51.8 preoperatively to 80.7 at 48 months postoperatively), IKDC (from 47.5 to 71.5), ICRS (from 3.8 to 2.0), KOOS (subcategory pain from 62 to 78, symptoms from 68 to 76, activities of daily living from 68 to 85, sports from 19 to 55, and quality of life from 30 to 55), and Noyes (from 31 to 59) scores (P ≤ .001) 48 months after implantation of BioSeed-C compared with the preoperative situation. The MRI evaluations showed moderate to complete defect filling in 43 of 44 treated patients. Two patients without improvement in the clinical and MRI scores received a total knee endoprosthesis after 4 years. Isokinetic evaluation showed significantly reduced maximum strength capacities for knee flexion and extension at the operated knee compared with the healthy knee (P<.05). Conclusion: The clinical outcomes 4 years after graft implantation are good despite a persisting strength deficit. Implanting Bio-Seed-C is a promising treatment option for cartilage defects of the knee. More emphasis should be put on the rehabilitation of muscular strength. © 2011 The Author(s).


Freymann U.,TransTissue Technologies GmbH | Endres M.,TransTissue Technologies GmbH | Endres M.,Charité - Medical University of Berlin | Neumann K.,TransTissue Technologies GmbH | And 4 more authors.
Acta Biomaterialia | Year: 2012

Treatment options for lesions of the avascular region of the meniscus using regenerative medicine approaches based on resorbable scaffolds are rare. Recent approaches using scaffold-based techniques for tissue regeneration known from cartilage repair may be a promising treatment option for meniscal tears. The aim of the study was the investigation of meniscus matrix formation of in vitro expanded human meniscus-derived cells in a three-dimensional (3-D) bioresorbable polymer graft for meniscal repair approaches. Cultivation of the human meniscus cells was performed in a resorbable scaffold material made of polyglycolic acid (PGA) and hyaluronic acid, stabilized with fibrin glue. Cell viability and distribution of human meniscus cells in PGA-hyaluronan scaffolds were evaluated by fluorescein diacetate and propidium iodide staining. Verification of typical meniscal extracellular matrix molecules like type I and type III collagen was performed histologically, immunohistochemically and by gene expression analysis. In results, 3-D scaffold-based meniscus cultures showed high cell viability over an observational period of 21 days in PGA-hyaluronan scaffolds. On the protein level, type I collagen and proteoglycans were evident. Gene expression analysis confirmed the re-expression of meniscus-specific markers in PGA-hyaluronan scaffolds. This study demonstrated that in vitro expanded human meniscus cells allow for formation of meniscal matrix components when cultured in 3-D PGA-hyaluronan scaffolds stabilized with fibrin. These results encourage scaffold-based approaches for the treatment of meniscal lesions. © 2011 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.


Pretzel D.,Friedrich - Schiller University of Jena | Linss S.,Friedrich - Schiller University of Jena | Ahrem H.,Jenpolymer Materials Ltd. and Co. KG | Ahrem H.,Friedrich - Schiller University of Jena | And 4 more authors.
Arthritis Research and Therapy | Year: 2013

Introduction: Current therapies for articular cartilage defects fail to achieve qualitatively sufficient tissue regeneration, possibly because of a mismatch between the speed of cartilage rebuilding and the resorption of degradable implant polymers. The present study focused on the self-healing capacity of resident cartilage cells in conjunction with cell-free and biocompatible (but non-resorbable) bacterial nanocellulose (BNC). This was tested in a novel in vitro bovine cartilage punch model. Methods: Standardized bovine cartilage discs with a central defect filled with BNC were cultured for up to eight weeks with/without stimulation with transforming growth factor-β1 (TGF-β1. Cartilage formation and integrity were analyzed by histology, immunohistochemistry and electron microscopy. Content, release and neosynthesis of the matrix molecules proteoglycan/aggrecan, collagen II and collagen I were also quantified. Finally, gene expression of these molecules was profiled in resident chondrocytes and chondrocytes migrated onto the cartilage surface or the implant material. Results: Non-stimulated and especially TGF-β1-stimulated cartilage discs displayed a preserved structural and functional integrity of the chondrocytes and surrounding matrix, remained vital in long-term culture (eight weeks) without signs of degeneration and showed substantial synthesis of cartilage-specific molecules at the protein and mRNA level. Whereas mobilization of chondrocytes from the matrix onto the surface of cartilage and implant was pivotal for successful seeding of cell-free BNC, chondrocytes did not immigrate into the central BNC area, possibly due to the relatively small diameter of its pores (2 to 5 μm). Chondrocytes on the BNC surface showed signs of successful redifferentiation over time, including increase of aggrecan/collagen type II mRNA, decrease of collagen type I mRNA and initial deposition of proteoglycan and collagen type II in long-term high-density pellet cultures. Although TGF-β1 stimulation showed protective effects on matrix integrity, effects on other parameters were limited. Conclusions: The present bovine cartilage punch model represents a robust, reproducible and highly suitable tool for the long-term culture of cartilage, maintaining matrix integrity and homoeostasis. As an alternative to animal studies, this model may closely reflect early stages of cartilage regeneration, allowing the evaluation of promising biomaterials with/without chondrogenic factors. © 2013 Pretzel et al.; licensee BioMed Central Ltd.


Enea D.,Marche Polytechnic University | Cecconi S.,Marche Polytechnic University | Calcagno S.,Sestri Levante Hospital | Busilacchi A.,Marche Polytechnic University | And 3 more authors.
Knee | Year: 2013

Background: Different single-stage surgical approaches are currently under evaluation to repair focal cartilage lesions. This study aims to analyze the clinical and histological results after treatment of focal condylar articular lesions of the knee with microfracture and subsequent covering with a resorbable polyglycolic acid/hyaluronan (PGA -HA) matrix augmented with autologous bone marrow concentrate (BMC). Methods: Nine patients with focal lesions of the condylar articular cartilage were consecutively treated with arthroscopic PGA -HA-covered microfracture and bone marrow concentrate (PGA -HA-CMBMC). Patients were retrospectively assessed using standardized assessment tools and magnetic resonance imaging (MRI). Five patients consented to undergo second look arthroscopy and 2 consented biopsy harvest. Results: All the patients but one showed improvement in clinical scoring from the pre-operative situation to the latest follow-up (average 22 ± 2. months). The mean IKDC subjective score, Lysholm score, VAS and the median Tegner score significantly increased from baseline to the latest follow-up. Cartilage macroscopic assessment at 12. months revealed that one repair appeared normal, three almost normal and one appeared abnormal. Histological analysis proofed hyaline-like cartilage repair tissue formation in one case. MRI at 8 to 12. months follow-up showed complete defect filling. Conclusions: The first clinical experience with single-stage treatment of focal cartilage defects of the knee with microfracture and covering with the PGA -HA matrix augmented with autologous BMC (PGA -HA-CMBMC) suggests that it is safe, it improves knee function and has the potential to regenerate hyaline-like cartilage. Level of evidence: IV, case series. © 2013 Elsevier B.V.


Kruger J.P.,TransTissue Technologies GmbH | Freymann U.,TransTissue Technologies GmbH | Vetterlein S.,TransTissue Technologies GmbH | Neumann K.,TransTissue Technologies GmbH | And 4 more authors.
Transfusion Medicine and Hemotherapy | Year: 2013

Introduction: The use of platelet-rich plasma (PRP) in regenerative approaches in cartilage repair is becoming more common. Information about PRP composition and its content of putative bioactive chondrogenic growth factors (GF) that may support cartilage regeneration is scarce. Methods: GF composition of a pool of 6 PRP preparations was determined using Protein Antibody Membrane Arrays covering 507 GF, signaling molecules, and receptors. To verify the chondrogenic GF variability in PRP, Growth Factor Antibody Membrane Arrays covering 26 GF were applied to 6 individual PRP preparations. Selected GF involved in chondrogenic differentiation were quantified by Enzyme-Linked Immunosorbent Assay (ELISA). Results: 417 out of 507 possible detectable proteins were present in the PRP pool, including 76 GF. Quantification of selected chondrogenic GF by ELISA showed an average of 0.31 ng/ml bone morphogenetic protein-2, 0.50 ng/ml connective tissue growth factor, 0.76 ng/ml fibroblast growth factor-2, and 0.59 ng/ml transforming growth factor-β3. Conclusion: PRP as a therapeutic option in regenerative cartilage repair strategies is a powerful tool for the local application of chondrogenic GF to the site of injury. Chondrogenic GF are present in PRP and may support cartilage repair by inducing cell differentiation and cartilage matrix formation. © 2014 S. Karger GmbH, Freiburg.


Kruger J.P.,TransTissue Technologies GmbH | Hondke S.,TransTissue Technologies GmbH | Endres M.,TransTissue Technologies GmbH | Endres M.,Charité - Medical University of Berlin | And 4 more authors.
Journal of Orthopaedic Research | Year: 2012

In cartilage repair, platelet-rich plasma (PRP) is used in one-step approaches utilizing microfracture and matrix-induced chondrogenesis procedures, bone marrow-derived cell transplantation, or intra-articular injection. The aim of our study was to evaluate the effect of human PRP on the migration and chondrogenic differentiation of human subchondral progenitors. Human progenitors were derived from subchondral cortico-spongious bone (CSP), were analyzed for their migration capacity upon PRP treatment in 96- well chemotaxis assays and cultured in high-density pellet cultures under serum-free conditions in the presence of 5% PRP. Chemotaxis assays showed that 0.1-100% PRP significantly (p < 0.05) stimulate the migration of CSP compared to untreated controls. Histological staining of proteoglycan and immuno-staining of type II collagen indicated that progenitors stimulated with PRP show significantly increased cartilage matrix formation compared to untreated progenitors. Real-time gene expression analysis of typical chondrocyte marker genes as well as osteogenic and adipogenic markers like osteocalcin and fatty acid binding protein showed that PRP induces the chondrogenic differentiation sequence of human progenitors in high-density pellet cultures, while osteogenic or adipogenic differentiation was not evident. These results suggest that human PRP may enhance the migration and stimulate the chondrogenic differentiation of human subchondral progenitor cells known from microfracture. © 2011 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.


Patrascu J.M.,Victor Babes University of Medicine and Pharmacy Timisoara | Freymann U.,Victor Babes University of Medicine and Pharmacy Timisoara | Freymann U.,TransTissue Technologies GmbH | Kaps C.,Victor Babes University of Medicine and Pharmacy Timisoara | And 2 more authors.
Journal of Bone and Joint Surgery - Series B | Year: 2010

Microfracture is frequently used as the first line of treatment for the repair of traumatic cartilage defects. We present the clinical and histological results 18 months to two-years after treatment in a 26-year-old male with a post-traumatic chondral defect of the medial femoral condyle managed by microfracture covered with chondrotissue, a cell-free cartilage implant made of a resorbable polyglycolic acid felt and hyaluronic acid. ©2010 British Editorial Society of Bone and Joint Surgery.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2011.1.4-2 | Award Amount: 4.29M | Year: 2012

This project will focus on the production of an in vitro human disease tissue platform technology to enable and accelerate the development of regenerative medicine therapies for a diverse range of diseases. The concept will be realised by the in vitro generation of 3D human tissues cultured from human induced Pluripotent Stem (iPS) cells. Initially a library of adult cells will be generated from patients with a range of genetic diseases. These cells will subsequently be used to generate iPS cell cultures in optimised conditions, with the resultant cells being differentiated into key cell types. These differentiated cells will then be integrated onto 3D tissue bioreactors operating in an optimised variable perfusion environment producing the 3D human tissue disease cultures. The bioreactors will be constructed using a range of innovative microfluidic techniques to produce systems compatible with analysis systems commonly used in laboratories worldwide. The development of a platform technology producing 3D human tissue disease cultures will enable the generation of fully differentiated cell types and thus allow diseases to be effectively modelled at a population relevant scale in 3D human tissues in vitro. The resultant major benefit of the system is that it will allow regenerative therapies to be developed and tested on batteries of human tissues in the laboratory in a rapid, cost effective manner relevant to the in vivo state. To develop and validate the platform technology within the lifetime of the project liver hepatocyte cells and tissues will be generated due to their scientific and commercial significance from a population relevant range of patients with inherited metabolic disorders (IMDs). Therefore this project will significantly advance the state of the art and constitute a significant step forward for the regenerative medicine industry producing a key platform resource.


Microfracture is a first-line treatment option for cartilage repair. In microfracture, subchondral mesenchymal cortico-spongious progenitor cells (CSP) enter the defect and form cartilage repair tissue. The aim of our study was to investigate the effects of joint disease conditions on the in vitro chondrogenesis of human CSP. CSP were harvested from the subchondral bone marrow. CSP characterization was performed by analysis of cell surface antigen pattern and by assessing the chondrogenic, osteogenic and adipogenic differentiation potential, histologically. To assess the effect of synovial fluid (SF) on chondrogenesis of CSP, micro-masses were stimulated with SF from healthy (ND), osteoarthritis (OA) and rheumatoid arthritis donors (RA) without transforming growth factor beta 3. CSP showed the typical cell surface antigen pattern known from mesenchymal stem cells and were capable of osteogenic, adipogenic and chondrogenic differentiation. In micro-masses stimulated with SF, histological staining as well as gene expression analysis of typical chondrogenic marker genes showed that SF from ND and OA induced the chondrogenic marker genes aggrecan, types II and IX collagen, cartilage oligomeric matrix protein (COMP) and link protein, compared to controls not treated with SF. In contrast, the supplementation with SF from RA donors decreased the expression of aggrecan, type II collagen, COMP and link protein, compared to CSP treated with SF from ND or OA. These results suggest that in RA, SF may impair cartilage repair by subchondral mesenchymal progenitor cells in microfracture, while in OA, SF may has no negative, but a delaying effect on the cartilage matrix formation.

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