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Cited by 65Osteoarthritis Treatment and MechanismsBone Tissue Engineering MaterialsTissue Engineering and Regenerative Medicine

The DOI matches its Crossref record; 159 of the 159 references it cites were found in a registry or an index.

Advances and prospects in biomimetic multilayered scaffolds for articular cartilage regeneration

Open access
Fu, Liwei, Yang, Zhen, Gao, Cangjian, Li, Hao, Yuan, Zhiguo, Wang, Fuxin, Sui, Xiang, Liu, Shuyun, Guo, Quanyi·2020·Regenerative Biomaterials
DOI 10.1093/rb/rbaa042PMC PMC7748444
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Abstract

Due to the sophisticated hierarchical structure and limited reparability of articular cartilage (AC), the ideal regeneration of AC defects has been a major challenge in the field of regenerative medicine. As defects progress, they often extend from the cartilage layer to the subchondral bone and ultimately lead to osteoarthritis. Tissue engineering techniques bring new hope for AC regeneration. To meet the regenerative requirements of the heterogeneous and layered structure of native AC tissue, a substantial number of multilayered biomimetic scaffolds have been studied. Ideal multilayered scaffolds should generate zone-specific functional tissue similar to native AC tissue. This review focuses on the current status of multilayered scaffolds developed for AC defect repair, including design strategies based on the degree of defect severity and the zone-specific characteristics of AC tissue, the selection and composition of biomaterials, and techniques for design and manufacturing. The challenges and future perspectives of biomimetic multilayered scaffold strategies for AC regeneration are also discussed.

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Figures

Figure 1. The five different layers of AC show zone-specific cell morphologies, matrix compositions, collagen fibril orientations and mechanical properties. (A) The content of collagen type X and GAG and compressive strain increase with depth, while the collagen type II concentration is inversely proportional to depth in the cartilaginous region. Subchondral bone is composed mainly of collagen type I and hydroxyapatite. (B) (1) The superficial zone has the highest density of chondrocytes and collagen fibres parallel to the joint surface. (2) The Middle zone has randomly oriented collagen fibres. (3) The deep zone has fibres perpendicular to the joint surface and tidemark, which is a basophilic line between uncalcified and calcified cartilage. (4) The calcified zone is the transition from cartilage to bone, and it has hypertrophic chondrocytes and anchors the fibres to the subchondral bone
Figure 1. The five different layers of AC show zone-specific cell morphologies, matrix compositions, collagen fibril orientations and mechanical properties. (A) The content of collagen type X and GAG and compressive strain increase with depth, while the collagen type II concentration is inversely proportional to depth in the cartilaginous region. Subchondral bone is composed mainly of collagen type I and hydroxyapatite. (B) (1) The superficial zone has the highest density of chondrocytes and collagen fibres parallel to the joint surface. (2) The Middle zone has randomly oriented collagen fibres. (3) The deep zone has fibres perpendicular to the joint surface and tidemark, which is a basophilic line between uncalcified and calcified cartilage. (4) The calcified zone is the transition from cartilage to bone, and it has hypertrophic chondrocytes and anchors the fibres to the subchondral boneCC BY · PubMed Central
Figure 2. Construction of multilayered scaffolds based on the zone-specific characteristics of AC tissue
Figure 2. Construction of multilayered scaffolds based on the zone-specific characteristics of AC tissueCC BY · PubMed Central
Figure 3. Classification of multilayered scaffolds according to the degree of defect severity. (A) An ideal biomimetic multilayered chondral scaffold. The surface layer is considered to protect the underlying layers from the stress in the joint, allowing cartilage repair and regeneration to occur without interference. The middle and deep layers should simulate the transition zone and the radial area of AC. The calcified layer, similar to calcified cartilage, contains biomineralization cues that make cartilage calcification and collagen type X deposition possible in this layer. (B) An ideal multilayered osteochondral scaffold. The construction of the cartilage layer simulates the zonal structure, and the bone layer simulates regenerated subchondral bone. The integration interface (calcified layer) between the cartilage and bone layers is very important
Figure 3. Classification of multilayered scaffolds according to the degree of defect severity. (A) An ideal biomimetic multilayered chondral scaffold. The surface layer is considered to protect the underlying layers from the stress in the joint, allowing cartilage repair and regeneration to occur without interference. The middle and deep layers should simulate the transition zone and the radial area of AC. The calcified layer, similar to calcified cartilage, contains biomineralization cues that make cartilage calcification and collagen type X deposition possible in this layer. (B) An ideal multilayered osteochondral scaffold. The construction of the cartilage layer simulates the zonal structure, and the bone layer simulates regenerated subchondral bone. The integration interface (calcified layer) between the cartilage and bone layers is very importantCC BY · PubMed Central
Figure 4. Biomaterials that are commonly applied in multilayered scaffolds
Figure 4. Biomaterials that are commonly applied in multilayered scaffoldsCC BY · PubMed Central
Figure 5. Common techniques for manufacturing multilayered scaffolds
Figure 5. Common techniques for manufacturing multilayered scaffoldsCC BY · PubMed Central
Figure 6. Future perspectives regarding multilayered scaffolds for AC regeneration. (A) The discontinuity in some multilayered scaffolds at the interface between layers limits the application of multilayered scaffolds. Continuous-gradient scaffolds will be promising with the development of fabrication technologies that can achieve a certain gradient accuracy. (B) Detailed knowledge of the properties of each biomaterial will help enhance the construction of biomimetic microenvironments through optimal material feature matching. (C) Appropriate manufacturing techniques might be beneficial in terms of the properties of multilayered constructs, such as the mechanical properties, porosity and pore size. (D) More importantly, future studies should explore specific and potent scaffolds with potential for successful clinical translation
Figure 6. Future perspectives regarding multilayered scaffolds for AC regeneration. (A) The discontinuity in some multilayered scaffolds at the interface between layers limits the application of multilayered scaffolds. Continuous-gradient scaffolds will be promising with the development of fabrication technologies that can achieve a certain gradient accuracy. (B) Detailed knowledge of the properties of each biomaterial will help enhance the construction of biomimetic microenvironments through optimal material feature matching. (C) Appropriate manufacturing techniques might be beneficial in terms of the properties of multilayered constructs, such as the mechanical properties, porosity and pore size. (D) More importantly, future studies should explore specific and potent scaffolds with potential for successful clinical translationCC BY · PubMed Central

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Metadata

Authors
Fu, L., Yang, Z., Gao, C., Li, H., Yuan, Z., Wang, F., Sui, X., Liu, S., & Guo, Q.
Affiliations
  • Nankai University (CN)
  • Shanghai Jiao Tong University (CN)
  • Chinese PLA General Hospital (CN)
Corresponding author
Guo, Quanyi
ORCID
Venue
Regenerative Biomaterials
Publisher
Oxford University Press (OUP)
Published
2020-09-30
Volume
7
Issue
6
Pages
527-542
ISSN
  • 2056-3418 (ISSN-L)
  • 2056-3426
DOI
10.1093/rb/rbaa042
PMC
PMC7748444
OpenAlex
W3091055634
Cited by
65
References
159
Citations by year
2026: 11 · 2025: 15 · 2024: 7 · 2023: 8 · 2022: 10 · 2021: 14
FWCI
1.24
Type
journal article
Language
en
Open access
Licence
Locations
  • Regenerative Biomaterials (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • National Key Research and Development Program of China (2019YFA0110600)
  • National Natural Science Foundation of China (81772319)
Topics
  • Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
  • Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
  • Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
Keywords
articular cartilage regeneration, multilayered scaffolds, biomimetic scaffolds, cartilage defects, osteoarthritis, biomaterial selection, scaffold fabrication, tissue engineering

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