Tendon and Bone Regeneration
Bones represent the supporting structure of the body, whereas the tendons allow our movement by transferring forces from the muscle to the bone. About 20% of all medical consultations are in the musculoskeletal area, of which about 30% are associated with tendon injuries. In addition to bone regeneration, the aim of our research group is to better understand tendon regeneration and thus to develop improved therapies for patients in the future.
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Under optimal conditions, bone can regenerate defect situations within a corresponding period of time without producing scar tissue. However, healing complications may occur after fracture, leading to non-unions. This can be due to mechanical as well as biological factors. Our research group deals primarily with biological aspects of bone healing.
Although bone, in contrast to tendons, ligaments or cartilages, has a good regeneration potential, severe complications still occur during bone healing. A better understanding of the healing process is therefore of particular importance. The focus of the group in this area is the investigation of the differences between the physiological healing in comparison to pathological changes caused for example by a disturbed vascularization. Through the use of small animal models, not only the variations in the healing phases can be studied, but also targeted manipulations, such as the inhibition of angiogenesis, can be carried out.
Furthermore, the treatment of non-unions by the local application of growth factors or bisphosphonates is an integral part of our research. The local application of stimulating factors can reduce the occurrence of systemic side effects and simultaneously lower the application dosage (for further information have a look at “Local application”).
In addition to histological investigations of the healing processes (Fig.1) and the visualization of new bone and vessel formation using micro-computer tomography and contrast agent (Fig.2), the molecular analysis of biological processes are also a focus of our research. Thus, in addition to osteogenic and angiogenic pathways, the influence of nitric oxide (NO) on bone healing is also investigated. NO is a gaseous signaling factor and the associated NO signaling pathway plays a crucial role in the regulation of many pathways and cellular processes. It is known that NO plays an important role in bone metabolism, but the interplay of NO with other signaling pathways of osteogenic differentiation is largely unknown. A deeper understanding on this interaction is important for the development of new as well as the optimization of existing therapies to treat impaired bone healing.
Bone grafting material
Large bony defects, without the potential to be bridged by the organism, must be treated with filling material to supply a structure for new bone formation. The gold standard for defect filling is the use of autogenic bony material. Due to complications associated with the harvesting of autogenic material, allogenic or alloplastic materials might be an alternative grafting material.
To improve materials used for defect filling, the material properties must be analyzed. The group has extensive experience in the analysis of bony materials used for defect filling. They have established a set-up that allows the quantification of growth factors within the bony grafting materials, the in vitro testing of the effect of the materials on different cell types (Fig. 3), and the efficacy testing of the materials in an animal critical size defect model. This approach allows a detailed analysis of existing and newly developed materials.
A further severe complication in bone healing is osteomyelitis and therefore the group aims to develop a prophylaxis and treatment for this complication. Osteomyelitis can be caused by several different bacteria and thus the correct antibiotic must be chosen for treatment. The combination of the adequate grafting material with a specific antibiotic and the optimal dosage and release will be important for a successful therapy (for further information have a look at “Local application”).
The knowledge of the biological processes during bone healing, the local stimulation potential and the analyses of grafting materials can be used for further development and optimization of treatment strategies. Those strategies can be combined to optimize the biomaterials by the addition of bioactive substances to stimulate bone regeneration or treat infections. This research aspect has direct clinical relevance and aims to develop new grafting materials for the stimulation and treatment of different patient-dependent bony defect situations.
- Authors:Kuehlfluck P, Moghaddam A, Helbig L, Child C, Wildemann B, Schmidmaier G, Group HT-HTRJournal:Injury Year:2015; Volume:46 Suppl 8:Pages:S23-32.
- Authors:Minkwitz S, Fassbender M, Kronbach Z, Wildemann B
Journal:PLoS One Year:2015; Volume:10Issue:(4):Pages:e0124217.
Title:Longitudinal analysis of osteogenic and angiogenic signaling factors in healing models mimicking atrophic and hypertrophic non-unions in rats
- Authors:Fassbender M, Minkwitz S, Thiele M, Wildemann B
Journal:Int Orthop Year:2014; Volume:38Issue:(9):Pages:1963-9.
Title:Efficacy of two different demineralised bone matrix grafts to promote bone healing in a critical-size-defect: a radiological, histological and histomorphometric study in rat femurs
- Authors:Nussler AK, Wildemann B, Freude T, Litzka C, Soldo P, Friess H, Hammad S, Hengstler JG, Braun KF, Trak-Smayra V, Godoy P, Ehnert S
Journal:Arch Toxicol Year:2014; Volume:88Issue:(4):Pages:997-1006.
Title:Chronic CCl4 intoxication causes liver and bone damage similar to the human pathology of hepatic osteodystrophy: a mouse model to analyse the liver-bone axis
- Authors:Hochrath K, Ehnert S, Ackert-Bicknell CL, Lau Y, Schmid A, Krawczyk M, Hengstler JG, Dunn J, Hiththetiya K, Rathkolb B, Micklich K, Hans W, Fuchs H, Gailus-Durner V, Wolf E, de Angelis MH, Dooley S, Paigen B, Wildemann B, Lammert F, Nüssler AK.Journal:Bone Year:2013; Volume:55Issue:(2):Pages:501-11.
- Authors:Garcia P, Histing T, Holstein JH, Klein M, Laschke MW, Matthys R, Ignatius A, Wildemann B, Lienau J, Peters A, Willie B, Duda G, Claes L, Pohlemann T, Menger MDJournal:Eur Cell Mater Year:2013; Volume:26:Pages:1-12; discussion 12-4.
- Authors:Histing T, Garcia P, Holstein JH, Klein M, Matthys R, Nuetzi R, Steck R, Laschke MW, Wehner T, Bindl R, Recknagel S, Stuermer EK, Vollmar B, Wildemann B, Lienau J, Willie B, Peters A, Ignatius A, Pohlemann T, Claes L, Menger MD
Journal:Bone Year:2011; Volume:49Issue:(4):Pages:591-9.
Title:Small animal bone healing models: standards, tips, and pitfalls results of a consensus meeting
- Authors:Fassbender M, Strobel C, Rauhe JS, Bergmann C, Schmidmaier G, Wildemann BJournal:Eur Cell Mater Year:2011; Volume:22:Pages:01. Nov.
- Authors:Ehnert S, Baur J, Schmitt A, Neumaier M, Lucke M, Dooley S, Vester H, Wildemann B, Stockle U, Nussler AKJournal:PLoS One Year:2010; Volume:5Issue:(11):Pages:e14073.
- Authors:Bormann N, Pruss A, Schmidmaier G, Wildemann BJournal:Arch Orthop Trauma Surg Year:2010; Volume:130Issue:(1):Pages:143-9.
- Authors:Herrmann M, Wildemann B, Wagner A, Wolny M, Schorr H, Taban-Shomal O, Umanskaya N, Ross S, Garcia P, Hubner U, Herrmann WJournal:J Bone Miner Res Year:2009; Volume:24Issue:(4):Pages:589-96.