Quantitative regulation of bone‐mimetic, oriented collagen/apatite matrix structure depends on the degree of osteoblast alignment on oriented collagen substrates

Abstract

Bone tissue has a specific anisotropic morphology derived from collagen fiber alignment and the related apatite crystal orientation as a bone quality index. However, the precise mechanism of cellular regulation of the crystallographic orientation of apatite has not been clarified. In this study, anisotropic construction of cell-produced mineralized matrix in vitro was established by initiating organized cellular alignment and subsequent oriented bone-like matrix (collagen/apatite) production. The oriented collagen substrates with three anisotropic levels were prepared by a hydrodynamic method. Primary osteoblasts were cultured on the fabricated substrates until mineralized matrix formation is confirmed. Osteoblast alignment was successfully regulated by the level of substrate collagen orientation, with preferential alignment along the direction of the collagen fibers. Notably, both fibrous orientation of newly synthesized collagen matrix and c-axis of produced apatite crystals showed preferential orientation along the cell direction. Because the degree of anisotropy of the deposited apatite crystals showed dependency on the directional distribution of osteoblasts cultured on the oriented collagen substrates, the cell orientation determines the crystallographic anisotropy of produced apatite crystals. To the best of our knowledge, this is the first report demonstrating that bone tissue anisotropy, even the alignment of apatite crystals, is controllable by varying the degree of osteoblast alignment via regulating the level of substrate orientation.

Disruption of Collagen Matrix Alignment in Osteolytic Bone Metastasis Induced by Breast Cancer

“…35) Thus, the traces of osteoclastic resorption form a scaffold for bone formation by osteoblasts. Considering that osteoblasts reside and synthesize the bone matrix dependently on the geometry of the substrate as demonstrated by an in vitro study, 36) the manner of osteoclastic resorption may determine the fate of subsequent osteo- In this study, the signi cant disruption of collagen matrix alignment in osteolytic bone metastasis was revealed for the rst time. In our model, extraordinarily ragged bone surfaces observed in the MM-231 metastatic bone presumably led to the random con guration of osteoblasts; hence, successively formed bone appeared to be randomly oriented, since we observed the defective alignment of collagen brils.…”

A paradigm shift for bone quality in dentistry: A literature review

“…Recent investigations revealed that osteoblast alignment is very important for the production of oriented BAp/ collagen structure. Osteoblast alignment can be achieved using metallic substrates with uni-directional periodic steps induced by plastic deformation [101,102] or laser-induced periodic surface structures (LIPSS) treatment [103], or collagen substrates with anisotropic molecular arrangement [104]. Osteoblastproduced collagen fibers and c-axis of precipitated BAp crystals show preferential orientation along the cell-elongated direction.…”

Directional Control of Mature Osteoblast Derived from Juvenile Mouse Calvariae

“…In addition, the preferential orientation of the osteoblasts was regulated using oriented collagen substrates as cell scaffolds, 8) which is crucial for constructing the anisotropic bone microstructure. 5) Our results clearly highlight the potential of juvenile mouse-derived osteoblasts (juvenile osteoblast) in construction of bone tissue with the original anisotropic microstructure.…”

“…Since cell orientation is a crucial factor for construction of the anisotropic bone architecture, 5,18,19) directional control of osteoblast was driven by oriented collagen substrates. In contrast to the rounded shape of osteoblasts observed on the cover glass (Fig.…”

“…We have reported that the degree of bone matrix anisotropy correlates quantitatively to the level of osteoblast alignment. 5) Therefore, isolation of functional osteoblasts and regulation of their arrangement for realizing ideal bone tissue constructs with optimally oriented microstructure is important.…”