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Review
. 2023 Feb 13;24(4):3744.
doi: 10.3390/ijms24043744.

The Use of Collagen-Based Materials in Bone Tissue Engineering

Affiliations
Review

The Use of Collagen-Based Materials in Bone Tissue Engineering

Lu Fan et al. Int J Mol Sci. .

Abstract

Synthetic bone substitute materials (BSMs) are becoming the general trend, replacing autologous grafting for bone tissue engineering (BTE) in orthopedic research and clinical practice. As the main component of bone matrix, collagen type I has played a critical role in the construction of ideal synthetic BSMs for decades. Significant strides have been made in the field of collagen research, including the exploration of various collagen types, structures, and sources, the optimization of preparation techniques, modification technologies, and the manufacture of various collagen-based materials. However, the poor mechanical properties, fast degradation, and lack of osteoconductive activity of collagen-based materials caused inefficient bone replacement and limited their translation into clinical reality. In the area of BTE, so far, attempts have focused on the preparation of collagen-based biomimetic BSMs, along with other inorganic materials and bioactive substances. By reviewing the approved products on the market, this manuscript updates the latest applications of collagen-based materials in bone regeneration and highlights the potential for further development in the field of BTE over the next ten years.

Keywords: bone substitute materials; bone tissue engineering; collagen; collagen modifications; composite bone scaffolds.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Hierarchical structure of type I collagen fiber and human bone.
Figure 2
Figure 2
Mechanisms of widely used chemical (A), physical (B), and biological (C) crosslinking technologies of collagen.
Figure 3
Figure 3
Schematic illustration of LC photo-crosslinking showing the organization and crosslinking of collagen following irradiation (adapted with citation [91]).
Figure 4
Figure 4
Widely used collagen-based medical devices for bone defect repair. (A) Porcine pericardium collagen membrane. (B) Lyophilized type I collagen sponge. (C) Scanning electron microscope (SEM) imaging of a cross-sectional view of a collagen membrane with a tightly packed smooth side at the bottom and a rough side on the top. (D) SEM image of lyophilized porous collagen sponge.
Figure 5
Figure 5
Clinical treatment of bone cysts. (A) Exposure of the mandible in the area of the cyst and opening. (B) Insertion of a xenogeneic bone substitute material, (C) covering with a pericardium-based collagen barrier membrane. (DF) Condition after bony healing at 3 months.
Figure 6
Figure 6
Exemplary histological images of the tissue response to a cross-linked collagen membrane (CC) within the subcutaneous connective tissue (CT) at day 30 post implantation. Black arrows = macrophages, black arrowheads = multinucleated giant cells, green arrows = fibroblasts, red arrows = eosinophilic granulocytes, and yellow arrows = lymphocytes (HE-staining, 200× magnification, scalebar = 20 µm).
Figure 7
Figure 7
Freeze-drying process of collagen sponge formation. Upon freezing, collagen molecules are entrapped within the developing ice crystals, which have formed into hexagonal structures.
Figure 8
Figure 8
Tissue reactions and integration behavior of a collagen sponge for hemostasis in dental applications at day 15 post implantation within the subcutaneous connective tissue (CT) of Wistar rats. (A) Overview of the implantation bed. A peripheral region (PR and double arrows) in which a cellular migration was noticed was separable from a nearly cell-free central region (CR), showing the gradual integration pattern of the biomaterial (Azan-staining, “total scan,” 100× magnification, scalebar = 5mm). (B) Tissue reaction within the PR including mainly macrophages (black arrows), as well as lower numbers of eosinophils (blue arrows) in combination with collagen fiber apposition (asterisks) and blood vessel ingrowth (red arrows) (Giemsa-staining, 400× magnification, scalebar = 10 µm). (C) Tissue reactions within the CR, including single macrophages (black arrows) within the interspaces of the collagen fibers (asterisks) of the sponge (Azan-staining, 400× magnification, scalebar = 20 µm).
Figure 9
Figure 9
Collagen sponge scaffold built up with self-assembled atelocollagen fibrils, which improved preosteoblast proliferation and differentiation, and bone formation effects in vivo. (Adapted with citation [129]).

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