TY  - JOUR
A1  - Fahmy-Garcia, Shorouk
A1  - Farrell, Eric
A1  - Witte-Bouma, Janneke
A1  - Robbesom-van den Berge, Iris
A1  - Suarez, Melva
A1  - Mumcuoglu, Didem
A1  - Walles, Heike
A1  - Kluijtmans, Sebastiaan G. J. M.
A1  - van der Eerden, Bram C. J.
A1  - van Osch, Gerjo J. V. M.
A1  - van Leeuwen, Johannes P. T. M.
A1  - van Driel, Marjolein
T1  - Follistatin Effects in Migration, Vascularization, and Osteogenesis in vitro and Bone Repair in vivo
JF  - Frontiers in Bioengineering and Biotechnology
N2  - The use of biomaterials and signaling molecules to induce bone formation is a promising approach in the field of bone tissue engineering. Follistatin (FST) is a glycoprotein able to bind irreversibly to activin A, a protein that has been reported to inhibit bone formation. We investigated the effect of FST in critical processes for bone repair, such as cell recruitment, osteogenesis and vascularization, and ultimately its use for bone tissue engineering. In vitro, FST promoted mesenchymal stem cell (MSC) and endothelial cell (EC) migration as well as essential steps in the formation and expansion of the vasculature such as EC tube-formation and sprouting. FST did not enhance osteogenic differentiation of MSCs, but increased committed osteoblast mineralization. In vivo, FST was loaded in an in situ gelling formulation made by alginate and recombinant collagen-based peptide microspheres and implanted in a rat calvarial defect model. Two FST variants (FST288 and FST315) with major differences in their affinity to cell-surface proteoglycans, which may influence their effect upon in vivo bone repair, were tested. In vitro, most of the loaded FST315 was released over 4 weeks, contrary to FST288, which was mostly retained in the biomaterial. However, none of the FST variants improved in vivo bone healing compared to control. These results demonstrate that FST enhances crucial processes needed for bone repair. Further studies need to investigate the optimal FST carrier for bone regeneration.
KW  - follistatin 315 (FST315)
KW  - follistatin 288 (FST288)
KW  - migration
KW  - vascularization
KW  - osteogenesis
KW  - injectable in situ gelling slow release system
KW  - bone tissue engineering
KW  - regenerative medicine
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227617
VL  - 7
ER  - 
TY  - JOUR
A1  - Jakob, Franz
A1  - Ebert, Regina
A1  - Rudert, Maximilian
A1  - Nöth, Ulrich
A1  - Walles, Heike
A1  - Docheva, Denitsa
A1  - Schieker, Matthias
A1  - Meinel, Lorenz
A1  - Groll, Jürgen
T1  - In situ guided tissue regeneration in musculoskeletal diseases and aging
JF  - Cell and Tissue Research
N2  - In situ guided tissue regeneration, also addressed as in situ tissue engineering or endogenous regeneration, has a great potential for population-wide “minimal invasive” applications. During the last two decades, tissue engineering has been developed with remarkable in vitro and preclinical success but still the number of applications in clinical routine is extremely small. Moreover, the vision of population-wide applications of ex vivo tissue engineered constructs based on cells, growth and differentiation factors and scaffolds, must probably be deemed unrealistic for economic and regulation-related issues. Hence, the progress made in this respect will be mostly applicable to a fraction of post-traumatic or post-surgery situations such as big tissue defects due to tumor manifestation. Minimally invasive procedures would probably qualify for a broader application and ideally would only require off the shelf standardized products without cells. Such products should mimic the microenvironment of regenerating tissues and make use of the endogenous tissue regeneration capacities. Functionally, the chemotaxis of regenerative cells, their amplification as a transient amplifying pool and their concerted differentiation and remodeling should be addressed. This is especially important because the main target populations for such applications are the elderly and diseased. The quality of regenerative cells is impaired in such organisms and high levels of inhibitors also interfere with regeneration and healing. In metabolic bone diseases like osteoporosis, it is already known that antagonists for inhibitors such as activin and sclerostin enhance bone formation. Implementing such strategies into applications for in situ guided tissue regeneration should greatly enhance the efficacy of tailored procedures in the future.
KW  - in situ guided tissue regeneration
KW  - stem cells
KW  - scaffolds
KW  - regenerative medicine
KW  - mesenchymal tissues
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-124738
VL  - 347
IS  - 3
ER  -