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. 2012:2:274.
doi: 10.1038/srep00274. Epub 2012 Feb 17.

Order versus Disorder: in vivo bone formation within osteoconductive scaffolds

Silvia Scaglione, Paolo Giannoni, Paolo Bianchini, Monica Sandri, Roberto Marotta, Giuseppe Firpo, Ugo Valbusa, Anna Tampieri, Alberto Diaspro, Paolo Bianco, Rodolfo Quarto

Order versus Disorder: in vivo bone formation within osteoconductive scaffolds

Silvia Scaglione et al. Sci Rep. 2012.

Abstract

In modern biomaterial design the generation of an environment mimicking some of the extracellular matrix features is envisaged to support molecular cross-talk between cells and scaffolds during tissue formation/remodeling. In bone substitutes chemical biomimesis has been particularly exploited; conversely, the relevance of pre-determined scaffold architecture for regenerated bone outputs is still unclear. Thus we aimed to demonstrate that a different organization of collagen fibers within newly formed bone under unloading conditions can be generated by differently architectured scaffolds. An ordered and confined geometry of hydroxyapatite foams concentrated collagen fibers within the pores, and triggered their self-assembly in a cholesteric-banded pattern, resulting in compact lamellar bone. Conversely, when progenitor cells were loaded onto nanofibrous collagen-based sponges, new collagen fibers were distributed in a nematic phase, resulting mostly in woven isotropic bone. Thus specific biomaterial design relevantly contributes to properly drive collagen fibers assembly to target bone regeneration.

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Figures

Figure 1
Figure 1. Electron microscopic analysis.
Significant differences in terms of micro-nano structure were observed between HA and HA-Col scaffolds (a–c and b–d respectively). At low magnification, HA foams show round-shaped interconnected pores, with black spots representing interconnections between neighbor pores (a). Ha-Col sponge, on the other side, shows a heterogeneous fibrous structure (b). At higher magnification, HA grains clearly form a substrate for cell adhesion, with black spots representing microporosity (c). Ha-Col scaffold highlights cells grasped to the collagen nanofibers (d). Bars: 200 μm, 500 nm respectively.
Figure 2
Figure 2. Histology of bone tissue.
Pattern of bone tissue deposited by stromal cells within HA and HA-Col grafts. The histological analysis was performed 1–2–6 months after implantation. b: bone; bm: bone marrow; ha: hydroxyapatite; ha-col: hydroxyapatite-collagen composite; ob: osteoblasts; oc: osteocytes; v: blood vessels. Arrows: lining cells. H&E staining. Bar: 50 µm.
Figure 3
Figure 3. SHG analysis of bone tissue.
(a) collagen fibers within HA scaffold 1–2 months after implantation. The images have been acquired by sequentially scanning the blue channel showing the forward scattered SHG signal and the grey channel showing the transmitted light trough the specimen. The forward scattered SHG signal of different portions of material has been also shown alone. (b) A histological view of the newly formed bone tissue and the corresponding forward scattered SHG signal were shown for both materials 6 months after implantation. Bar: 5 µm.
Figure 4
Figure 4. TEM analysis and collagen pattern within bone tissue.
(a) the interface neobone-HA scaffold 2 months after implantation. Note several collagen fibers branching inside the ceramic substitute. (b) and (c) are high magnifications of (a), showing the characteristic banding pattern of the collagen fibrils. (d) shows the organized bone tissue deposited within a representative pore of HA scaffold. Regular series of nested arcs, typical of mature bone tissue, were observed. The inset (e) is an enlarged view of the bone tissue region, where the typical band of collagen fibers is visible. Bars: 2 μm; 0.2 μm; 0.1 μm; 1.25 μm; 0.4 μm.
Figure 5
Figure 5. Model of collagen fibers assembly over time.
As soon the osteoprogenitor cell interacts and decodes the ceramic surface (a). it synthesizes and deposits collagen molecules that resemble rods infiltrating the micropores of the HA foam. Cells are therefore induced to deposit newly formed bone tissue in a polarized fashion (b–c–d). On the other side, the nanofibrous Ha-Col sponge offers to the cells a disordered and isotropic microenvironment (e). where deposit collagen fibers in a random 3D geometry (f–g–h). Model showing collagen fibrils assembly in the extracellular matrix by the cells within a HA regular and ordered scaffold is shown (i).
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