TRR 79:
Materials for Tissue Regeneration within Systemically Altered Bone
Subject Area
Medicine
Chemistry
Materials Science and Engineering
Mathematics
Term
from 2010 to 2019
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 107540325
Treatment of fractures and defects in systemically altered hard tissue represents one of the major challenges in medicine. Represented by patients suffering from bone defects or pathological fractures related to osteoporosis or tumor diseases, as exemplified by multiple myeloma, bone healing is impaired and associated with complications, related to altered remodeling and biochemical properties of bone and, in multiple myeloma, additionally by the presence of the malignant cell population causing the defect. In these conditions, the integration of bone substitute materials, their “anchoring”, and long-term stability are severely impeded. The long-term aim of our TRR 79 is thus to develop a material concept laying the basis for an etiology-based development of bone substitute materials and implants. Within the third funding period and in collaboration with industrial partners, metallic implants and bone substitute materials developed for osteoporotic bone enter the translation-phase for clinical application. For the first time, our results allow meeting a second major clinical challenge, a local treatment of multiple myeloma in specific situations per se: Material properties and compounds released locally at high concentrations shall first eliminate residual myeloma cells after successful treatment, and secondly bring resistant myeloma cells under control locally, thereby avoiding further bone destruction. Furthermore, results in the second funding period lay the basis for a whole-body-detection of minimum numbers of tumor cells.Unique features of our SFB/TRR 79 initiative are: i) bone substitute materials and metallic implants are developed taking into account biomechanics, architecture and altered remodeling in systemically diseased bone in relation to the underlying disease (“etiology-adapted”). ii) Synergistically, bone defects in osteoporosis and malignant diseases are investigated simultaneously. iii) For the first time, materials are specifically developed for a local treatment of multiple myeloma. iv) Within our concept, the life sciences present themselves “at the service” of material development, simultaneously integrating state-of-the-art techniques in molecular biology and imaging. Investigations in men, animal experiment, and cell culture are linked and feed back to material development. At the same time, they investigate own basic research questions related to specific topics, e.g. immunological elements of osteoporosis and multiple myeloma pathogenesis. The complexity of this challenge prerequisites an interdisciplinary collaboration of a synergistically acting research-consortium of “critical mass” (as the SFB/Transregio-initiative). Here we combine the complementary expertise at the different locations: Dresden – material science (bone substitute material and implants), Gießen – non-malignant bone defects (pathophysiology of osteoporosis, imaging) and animal models, and Heidelberg – life sciences, imaging and multiple myeloma.
DFG Programme
CRC/Transregios
Completed projects
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01 - Development of new Ti-based alloys for improvement of the anchoring and fracture healing of diseased bones
(Project Heads
Eckert, Jürgen
;
Gebert, Annett
;
Zimmermann, Martina
)
-
02 - Calcium phosphate bone cements for local therapy of defects of the systemically diseased bone
(Project Heads
Gelinsky, Michael
;
Lode, Anja
)
-
03 - Composite based on collagen, silica and calcium phosphate for bone replacement
(Project Heads
Hanke, Thomas
;
Kruppke, Benjamin
;
Worch, Hartmut
)
-
04 - Establishment of an ‘in situ tissue engineering’-approach for bone defect healing
(Project Heads
Gelinsky, Michael
;
Rösen-Wolff, Angela
)
-
05 - Interfacial chemistry and 3-D analysis of interfaces of implants and osteoporotic bone
(Project Heads
Janek, Jürgen
;
Rohnke, Marcus
)
-
06 - Biofunctionalized addressable polyelectrolyte based nanoparticles for the controlled release of drugs related to hard tissue regeneration
(Project Heads
Appelhans, Dietmar
;
Müller, Martin
)
-
07 - Mathematical modelling and simulation of bone and implant remodelling in the healthy and diseased bone
(Project Heads
Bobeth, Manfred
;
Cuniberti, Gianaurelio
;
Deutsch, Andreas
;
Marciniak-Czochra, Anna
;
Voigt, Axel
)
-
08 - Functionalized hydrogels presenting simultaneously β1-integrin selective ligands and bone morphogenic protein 6 to stimulate osteoblast function and induce myeloma cell apoptosis
(Project Heads
Cavalcanti-Adam, Elisabetta Ada
;
Seckinger, Anja
)
-
09 - Bone destruction in multiple myeloma: pathogenesis and model as basis for therapeutic targeting of bone substance defects by etiology-based bone substitute material
(Project Heads
Goldschmidt, Hartmut
;
Hose, Dirk
)
-
10 - Influence of multiphase-bone replacement materials and surface-modified titanium alloys on the differentiation of osteoblasts/MSC
(Project Heads
Arnhold, Stefan
;
Hempel, Ute
)
-
11 - Modification of cell-cell and cell-matrix communication within bone tissue by new materials
(Project Heads
Cavalcanti-Adam, Elisabetta Ada
;
Hackstein, Holger
;
Hose, Katja Anette
;
Lips, Katrin Susanne
;
Wenisch, Sabine
)
-
12 - Influence of aetiology-adapted bone substitutes on the regulation of bone remodeling, microvascularisation and innervation in systemically diseased bone
(Project Heads
Kilian, Olaf
;
Lips, Katrin Susanne
)
-
13 - Investigation of bone defects and microcirculation with volume computed tomography and dy-namic contrast-enhanced magnetic resonance imaging
(Project Heads
Bäuerle, Tobias
;
Delorme, Stefan
;
Hillengaß, Jens
;
Komljenovic, Dorde
)
-
14 - Quantitative studies of metabolism (F-18-deoxyglucose) and bone metabolism (F-18-fluoride) with dynamic positron emission tomography-computed tomography (dPET-CT)
(Project Heads
Dimitrakopoulou-Strauss, Antonia
;
Goldschmidt, Hartmut
;
Strauss, Ludwig Georg
)
-
15 - Cellular differences in sensitivity against drug releasing bone substitute materials within physiological and pathological bone remodeling
(Project Heads
Burhenne, Jürgen
;
Seckinger, Anja
;
Weiß, Johanna
)
-
16 - Structural and cellular characterization of bone marrow interfaces under the influence of adi-pogen factors in bone replacement material testing
(Project Heads
Müller-Ladner, Ulf
;
Neumann, Elena
;
Rohnke, Marcus
;
Schnettler, Reinhard
;
Wenisch, Sabine
)
-
17 - Molecular characterization of interactions between bone-substitute material and surrounding tissue in sheep, rat, and myeloma-mouse-model by transcriptome profiling using next generation RNA-Sequencing and functional validation
(Project Heads
Böcker, Wolfgang
;
Hose, Dirk
;
Neumann, Elena
;
Rösen-Wolff, Angela
)
-
18 - Characterization and identification of osteoporotic animal models
(Project Heads
Böcker, Wolfgang
;
El Khassawna, Thaqif
;
Heiß, Christian
;
Schnettler, Reinhard
)
-
19 - Stimulation of bone defect and fracture healing in systemically impaired bone by biomaterials and metallic implants
(Project Heads
Alt, Volker
;
Schnettler, Reinhard
;
Thormann, Ulrich
)
-
20 - Central Administration
(Project Heads
Heiß, Christian
;
Schnettler, Reinhard
)
-
21 - Local structure analysis by high resolution transmission electron microscopy
(Project Heads
Eckert, Jürgen
;
Gemming, Thomas
;
Kniep, Rüdiger
;
Simon, Paul
)
-
22 - Imaging of Systemic Bone Pathology and its Therapy using Micro- and Nano-CT Technology
(Project Heads
Kampschulte, Marian
;
Obert, Martin
)
-
B02 - Characterization of callus tissue within systemically altered bone
(Project Heads
Hose, Dirk
;
Wenisch, Sabine
)
-
B06 - The influence of bone substitute biomaterial on angiogenesis applied at bone defects caused by benign and malignant diseases
(Project Heads
Möhler, Thomas
;
Schwartz-Albiez, Reinhard
;
Willhauck-Fleckenstein, Martina
)
-
M06 - Surface patterning and functionalization strategies for targeted bone cell adhesion and response
(Project Heads
Cavalcanti-Adam, Elisabetta Ada
;
Spatz, Joachim P.
)