Metal-doped silicate microparticles for collagen scaffold-guided endochondral bone regeneration

Endochondral ossification (EO) describes a process in which bone tissue builds up via a cartilaginous phase. In contrast to classical biomaterial approaches, which address bone regeneration via direct, intramembranous ossification (IO), a collagen scaffold was shown to stimulate endochondral healing of large bone defects. Here, its unique intrinsic bioactivity relied solely on its architecture without the need for progenitor cell seeding or the application of growth factors. To investigate how material components can have a bioactive contribution to the required cartilage formation during endochondral ossification (EO), this architecture-driven biomaterial approach was combined with the release of therapeutic metal ions. Silicate microparticles were chosen as a delivery platform for lithium, magnesium, strontium, or zinc ions, each of which is known to have a beneficial effect on cartilage and bone formation. An extensive in vitro evaluation, including the determination of the materials' physical properties as well as the bioactivity of ten fabricated hybrid scaffolds, was performed. An ion-specific cellular reaction was observed, wherein certain metal ions notably boosted the recruitment of cells into the material and displayed enhanced secretion of collagen II and chondrogenesis by human mesenchymal stromal cells (MSCs). Simultaneously, microparticle incorporation changed the mechanical characteristics of certain hybrid scaffolds, affecting cell-mediated material contraction and deformation of the scaffold walls. Endochondral bone formation, induced by the investigated collagen scaffold and during bone development, is a well-orchestrated differentiation process. Delivering anisotropic cellular cues in the form of biomolecular gradients plays an essential role, which results in the typical columnar, zonal organization of cells at different maturation stages. To recapitulate the structural aspects of the observed scaffold-guided tissue formation, a novel in vitro culture system was developed, which allows for EO-resembling spatiotemporal stimulation. Although certain limitations of the system were identified, the EO tissue polarization within collagen scaffold-MSCs constructs was successfully reproduced as observed previously in vivo. After cultivation, constructs displayed zones of chondrocytes, hypertrophic chondrocytes and matrix calcification. In summary, the results from evaluating different hybrid scaffolds indicated that the incorporation of metal-doped silicates has the potential to further increase the bioactivity of collagen scaffolds for endochondral bone regeneration. Secondly, an in vitro culture system was successfully developed that allows the recapitulation of EO in collagen scaffolds, serving as a valuable methodology for an advanced in vitro evaluation of future scaffold candidates.

Author dc:creator

• Stadter, Janina

Advisor dc:contributor.advisor

• Kurreck, Jens

Licence dc:rights.uri

• https://creativecommons.org/licenses/by/4.0/

Language dc:language.iso

en

Identifier URI

https://doi.org/10.14279/depositonce-23856

OAI identifier oai:identifier

oai:depositonce.tu-berlin.de:11303/25039