Günter Lauer

Cell-based approach to fracture repair

Previous and current research

Lack of or deficits in hard and soft tissue of the skull and the face due to tumour therapy, trauma or degenerative pathologies are a recurrent issue in Oral and Maxillofacial Surgery. The standard therapy involves the use of transplants or other technical devices like osteo- distractors. Cell based regenerative therapy like tissue engineering offer new perspectives.

In our group we are developing cell based strategies to treat such soft and hard tissue deficits.

For soft tissue regeneration mucosa grafts are generated and tested in animals and in case controlled studies on humans. To simplify the application of such grafts one focus is also to develop cryopreservation methods in cooperation with Institute of air conditioning and cryotechnology, Dresden. The cell and tissue survival during the cryopreservation process in vitro and the take of the cryopreserved grafts are assessed.

For hard tissue regeneration, cell based approaches to enhance bone growth have been inaugurated. Therefore, the transplantation of osteoblasts e.g. in cysts have been used in case control studies on humans demonstrating that ossification is as good as bone grafts from the hip. Further, osteoblasts on carrier material implanted in muscle of rats instigate ectopic bone formation. To find approaches to accelerate bone healing in fractures we are now focusing on the use of mesenchymal (MSC) and haematopoietic (HSC) stem cell the precursor cells of the bone building and the bone digesting cells. A mouse model has been established where in fractures, defect fractures and other bone defects bone healing can be assessed after transplanting MSC and HSC. Therefore, histological and immunohistological techniques are available in cooperation within the CRTD cellbiological means are used to evaluate bone growth. Further, these techniques are also used to manipulate these cells in their lineage towards differentiated cells. Another issue in these transplantation experiments is to track these cells after transplantation in the organism. Therefore, different concepts based on direct labelling of cells, transfection, transduction and postmortal identification of Y-chromosome in the transplanted stem cells or transplantation of labelled cells (GFP – mice) are established.

Figure 1: Radiograph of cyst in the mandible (region of the wisdom tooth) before surgery. There is a radiolucency (arrows).	Figure 2: Radiograph of cyst in the immediately after surgery. There is no change in radiolucency (arrows) as the graft material (cells and collagen carrier material is not radioopaque).	Figure 3: Radiograph of cyst in the mandible 10 months after surgery. There is no radiolucency (arrows) but an evenly structured formation of bone, giving evidence that the cyst is completely ossified

Future prospects and goals

The aim of this proposal is to compare the influence of implanted mesenchymal and haematopoietic stem cells (MSC, HSC) and their derived cells of the bone cell lineage on the healing of different kind of fractures in healthy and compromised bones. We have established a bone-healing assay using as a model the fracture of the femur in mice. With this assay, the following questions can be addressed:

• How efficient is the repair of bone fractures by normal MSC and derived osteoblasts in animals without or with bone pathology? As a convenient way of monitoring grafted cells, green fluorescent protein (GFP) expressing MSC and HSC (isolated from GFP transgenic mice) and injected at different sites (fracture, bone marrow, peripheral vein) of wild type animals with a fractured limb.
• What is the influence of osteoblasts in bone healing? A similar approach can be used for MSC and derived osteoblasts.
• What is the influence of osteoclasts and their progenitors the HSC on bone repair?

About

1982-1987: Medical Doctoral thesis, University of Heidelberg, Germany 1988-1991: Dental Doctoral thesis, University of Freiburg, Germany 1998: Habilitation in Oral and Maxillofacial Surgery, University of Freiburg, Germany 1990-2000: Clinical and Research Assistant at the Department of Oral and Maxillofacial Surgery, University of Freiburg, Germany 1994: Specialist in Oral and Maxillofacial Surgery 1997: Head Outpatient Clinic at at the Department of Oral and Maxillofacial Surgery 1998: Plastic Surgery in the Oral & Maxillofacial region 1998: Consultant (Senior physician) at the Department of Oral and Maxillofacial Surgery since 2000: Deputy Head Department of Oral and Maxillofacial Surgery, University Hospital Carl Gustav Carus Dresden, University of Technology, Germany

Selected publications

Lauer G, Wiedmann Al Ahmad M, Otten JE, Hübner U, Schilli W (2001): The titanium surface texture effects the adherence and growth of human gingival keratinocytes and human maxillar osteoblast-like cells in vitro. Biomaterials 22: 2799-2809                            
Lauer G, Siegmund C, Hübner U (2005): Influence of Donor Age and Culture Conditions on Tissue Engineering of Mucosa Autografts
Int J 0ral Maxillofac Surg 32: 305-312 (2003)                           

Mai R, Reinsdorf A, Pilling E, Lauer G, Gelinsky M, Eckelt U. Custom moldable hydroxyapatite collagen composite for repair of osseous defects. Mund Kiefer Gesichtschir 9:12-17

Pradel W, Tenbieg P, Lauer G (2005): Influence of harvesting technique and donor site localization on in-vitro growth of osteoblastlike cells from facial bone. Int J. Oral Maxillofac Impl 20: 860-6                  

Pradel W, Eckelt U, Lauer G (2006): Bone Regeneration after Enucleation of Mandibular Cysts Comparing Autogenous Grafts from Tissue Engineered Bone and Iliac Bone.  Oral Surg Oral Med Oral Path Oral Radiol Endod 101:285-290                

Mai R, Hagedorn MG, Gelinsky M, Werner C, Turhani D, Gedrange T, Lauer G (2006): Ectopic bone formation in nude rats using human osteoblasts seeded poly(3)hydroxybutyrate embroidery and hydroxyapatite-collagen tapes constructs. J Cranio Maxillofac Surgery 34, Suppl 2:101-9

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