Schlüsselwörter
(Englisch)
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Critical sized bone defect; Cell therapy; Bio-functional; Self-assembly; Hydrogel; Hyaluronan; Vascularisation; Mesenchymal stromal cells
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Forschungsprogramme
(Englisch)
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COST-Action MP1005 - From nano to macro biomaterials (design, processing, characterization, modeling) and applications to stem cells regenerative orthopedic and dental medicine (NAMABIO).
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Kurzbeschreibung
(Englisch)
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Due to diverse pathological processes such as trauma, tumor, in?ammation, infection and congenital malformations, critical size bone defects do not heal spontaneously during the patients lifetime if left untreated. Thus, successful treatment of critical sized bone defects (CSD) remains a major clinical problem. Bone is a complex and hierarchical tissue, which is a highly vascularised and mineralized material composed of multiple cells and molecules. Its regeneration depends on a complex orchestration of a variety of physical and biomolecular signals with spatio-temporal control. One of the major difficulties in achieving functional engineered repair has been, and still is the successful generation of biomaterials with the capacity to control and biomimetically recreate such multiple mechanical, structural and biological signals. The goal of our research is to create an innovative biofunctional self-assembling hyaluronan hydrogel capable of inducing rapid vascularisation. We will evaluate the potential of a regenerative approach to CSD healing based on the combination of the new biomaterial with human autologous bone marrow derived mesenchymal stromal cells (MSCs) loaded in a biodegradable poly(ester-urethane) scaffold providing macro-structural and mechanical stabilities.
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Weitere Hinweise und Angaben
(Englisch)
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Full name of research-institution/enterprise: AO Research Institute Davos Head of Musculoskeletal Regeneration Scientific Editor eCM
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Partner und Internationale Organisationen
(Englisch)
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AT; BE; BA; BG; HR; CY; CZ; DK; EE; FI; FR; F.Y.R. Macedonia; DE; EL; HU; IS; IE; IL; IT; LV; MT; NL; NO; PL; PT; RO; RS; SK; SI; ES; SE; TR; UK
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Abstract
(Englisch)
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Due to diverse pathological processes such as trauma, tumor, inflammation, infection and congenital malformations, large size bone defects do not heal spontaneously upon classical care and new therapeutic approaches are needed. Classical bone tissue engineering (TE) typically uses bone substitutes consisting of cells and a carrier matrix or scaffold, generating bone tissue by a process resembling intramembranous ossification and direct osteoblastic differentiation. Several factors such as addition of osteogenic stimuli, growth factors, and the osteogenic properties of the scaffold have shown to influence in vivo bone formation. However, optimal and reliable repair outcome in a large range of cases has not been achieved so far. In the context of skeletal tissue repair, the principle of engineering processes targets the engineering of bone through endochondral ossification, the embryonic development pathway of long bones. The natural process of endochondral bone formation is associated with several advantages when translated to approaches for bone TE. It has the potential to overcome issues critical to the functioning of engineered bone grafts, such as resistance to hypoxic conditions, vascularization and mechanical stability. The promise and limitations of differentiating human mesenchymal stem cells (hMSCs) through the endochondral route for bone TE were shown recently. Though, the impact of bone process engineering has not yet been discussed in respect to biomaterials properties and design. In vivo and in vitro investigations using hypertrophic cartilage templates are principally reported in the literature with several important findings establish a central role of scaffold properties in directing developmental bone regeneration. The intention of this project is therefore to elucidate the biomaterials physical and chemical cues that could be manipulated to direct hypertrophic differentiation of different cell types and finally control endochondral bone TE process in vitro. Tyramine based hyaluronan conjugates (HA-Tyr) able to form hydrogel upon exposure to horseradish peroxidase and hydrogen peroxide were synthesized and characterized in the first part of the project. Next, an alternative crosslinking method using visible light illumination was developed and allowed spatio-temporal control of HA-Tyr hydrogel formation. The influence of biophysical cues, such as stiffness and gelation mode of HA-Tyr substrates on cell behavior and proliferation was shown in 2D and 3D. For future studies the aim is to investigate the ability of hMSCs encapsulated in HA-Tyr hydrogels to form bone through hypertrophic cartilage in vivo.
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Datenbankreferenzen
(Englisch)
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Swiss Database: COST-DB of the State Secretariat for Education and Research Hallwylstrasse 4 CH-3003 Berne, Switzerland Tel. +41 31 322 74 82 Swiss Project-Number: C11.0126
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