Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 May 18:20:29-40.
doi: 10.1016/j.bioactmat.2022.04.030. eCollection 2023 Feb.

Nano-calcium silicate mineralized fish scale scaffolds for enhancing tendon-bone healing

Fei Han  1 , Tian Li  1   2 , Mengmeng Li  1 , Bingjun Zhang  1 , Yufeng Wang  3 , Yufang Zhu  1   2 , Chengtie Wu  1   2
Affiliations

Nano-calcium silicate mineralized fish scale scaffolds for enhancing tendon-bone healing

Fei Han et al. Bioact Mater. .

Abstract

Tendon-bone healing is essential for an effective rotator cuff tendon repair surgery, however, this remains a significant challenge due to the lack of biomaterials with high strength and bioactivity. Inspired by the high-performance exoskeleton of natural organisms, we set out to apply natural fish scale (FS) modified by calcium silicate nanoparticles (CS NPs) as a new biomaterial (CS-FS) to overcome the challenge. Benefit from its "Bouligand" microstructure, such FS-based scaffold maintained excellent tensile strength (125.05 MPa) and toughness (14.16 MJ/m3), which are 1.93 and 2.72 times that of natural tendon respectively, allowing it to well meet the requirements for rotator cuff tendon repair. Additionally, CS-FS showed diverse bioactivities by stimulating the differentiation and phenotypic maintenance of multiple types of cells participated into the composition of tendon-bone junction, (e.g. bone marrow mesenchymal stem cells (BMSCs), chondrocyte, and tendon stem/progenitor cells (TSPCs)). In both rat and rabbit rotator cuff tear (RCT) models, CS-FS played a key role in the tendon-bone interface regeneration and biomechanical function, which may be achieved by activating BMP-2/Smad/Runx2 pathway in BMSCs. Therefore, natural fish scale -based biomaterials are the promising candidate for clinical tendon repair due to their outstanding strength and bioactivity.

Keywords: Bioactivities; Fish scales; High strength; Tendon repair; Tendon-bone healing enhancement.

PubMed Disclaimer

Figures

Image 1
Graphical abstract
Fig. 1
Fig. 1
Schematic summarizing work on the fabrication of calcium silicate (CS)-"bioactivated” fish scale scaffold (CS-FS) by vacuum-induced mineralization, for tendon defect repair. In the vacuum-induced mineralization process, Ca2+ ions can engage in coordinating chelation interactions with the carbonyl and carboxyl groups of collagen fibers in fish scale and subsequently combined with SiO32− ions to induce the in situ formation of CS particle. The silicon and calcium ions released from CS-FS contributed to the regeneration of tendon-bone interface and the healing of tendon defect.
Fig. 2
Fig. 2
Microstructure and morphology of CS-FS scaffolds with different CS mineralization level. (A to F) Scanning electron microscope (SEM) images presented the internal microstructure and different mineralization levels of CS-FS scaffolds in each group. In addition, the attached schematic diagram shows the structure changes of each group. (G) High-resolution transmission electron microscopy (HRTEM) images showed the pattern of the deposited CS produced by vacuum-induced mineralization on the FS collagen fibers. The CS particles which are evenly distributed along the collagen fibers were observed. (H) Energy spectrum analysis confirmed that the particles observed in HRTEM images were CS.
Fig. 3
Fig. 3
Mechanical properties of CS-FS scaffolds. Comparison of (A) maximum tensile strength, (B) Toughness, and (C) Young's modulus of untreated FS (O-FS), different CS-FS scaffolds and natural tendon. (The data of natural tendons obtained from previously reported study [38].) Tensile stress-strain curves (D) and Strain at failure (E) of O-FS and each CS-FS scaffold. (F) Ashby diagram of toughness and young's modulus for reported tendon tissue engineering scaffolds [[63], [64], [65], [66], [67], [68], [69], [70], [71], [72], [73], [74]]. This indicates that the mechanical strength of CS-FS scaffolds with a certain amount of mineralization is completely suitable for tendon repair.
Fig. 4
Fig. 4
The CLSM images of the specific markers and Q-PCR analysis of specific gene expression for BMSCs, Chondrocytes and TSPCs cultured on CS-FS scaffolds in each group. The CLSM images showed the fluorescence labelled (A) Opn in BMSCs, (B) N-cadh in Chondrocytes and (C) Col 1 in TSPCs. Bar 100 μm (D) Expression of osteogenic differentiation-related genes in BMSCs cultured on each CS-FS scaffold. (E) Expression of chondrocytes phenotype-related genes in Chondrocytes cultured on each CS-FS scaffold. (F) Expression of tenogenic differentiation-related genes in TSPCs cultured on each CS-FS scaffold. CS deposition improved the bioactivity of FS scaffolds which promoted cell differentiation of several tissue cells.
Fig. 5
Fig. 5
Histopathological analysis and biomechanical analysis of the therapeutic effect of CS-FS scaffolds on RCT in rabbit models. (A) The images of safranin-o-fast green staining, H&E staining and Masson’ s staining showed the healing of tendon-bone interface and the regeneration of fibrocartilage in each group 12 weeks after surgery. (B) The images of H&E staining illustrated the integration of each scaffolds with injured host tendon stump and host bone, and the growth of new tendon tissue and new bone tissue between scaffold and host tissue. ‘T’ in the figures represents the host tendon, that is, the injured host tendon stump; ‘B’ refers to the host bone; ‘I’ identifies the tendon-bone interface; ‘S’ represents the scaffold; ‘NT’ refers to new tendon tissue or bone tissue between scaffold and host tissue. (C) A brief schematic diagram of the RCT repair using CS-FS in rabbit models. (D) Quantitative analysis of the relative area of fibrocartilage tissue at the regenerated tendon-bone interface which was executed based on the images of safranin-o-fast green staining. (E) Histological score, the scoring rules followed previous studies and 4 colleagues performed a double-blind scoring. (F to H) Biomechanical analysis of repaired rotator cuff tendon in each group 12 weeks after surgery. The detection items are (F) Ultimate failure load, (G) Ultimate stress and (H) stiffness. n = 4, *P < 0.05, **P < 0.01, ***P < 0.001.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Aagaard K.E., Abu-Zidan F., Lunsjo K. High incidence of acute full-thickness rotator cuff tears A population-based prospective study in a Swedish Community. Acta Orthop. 2015;86(5):558–562. doi: 10.3109/17453674.2015.1022433. - DOI - PMC - PubMed
    1. Lantto I., Heikkinen J., Flinkkila T., Ohtonen P., Leppilahti J. Epidemiology of Achilles tendon ruptures: increasing incidence over a 33-year period. Scand. J. Med. Sci. Sports. 2015;25(1):E133–E138. doi: 10.1111/sms.12253. - DOI - PubMed
    1. Moses B., Orchard J., Orchard J. Systematic review: annual incidence of ACL injury and surgery in various populations. Res. Sports Med. 2012;20(3–4):157–179. doi: 10.1080/15438627.2012.680633. - DOI - PubMed
    1. Sharma P., Maffulli N. Current concepts review tendon injury and tendinopathy: healing and repair. J. Bone Joint Surg.-Am. 2005;87A(1):187–202. doi: 10.2106/JBJS.D.01850. - DOI - PubMed
    1. Rudzki J.R., Adler R.S., Warren R.F., Kadrmas W.R., Vermc N., Pearle A.D., Lyman S., Fealy S. Contrast-enhanced ultrasound characterization of the vascularity of the rotator cuff tendon: age- and activity-related changes in the intact asymptomatic rotator cuff. J. Shoulder Elbow Surg. 2008;17(1):96S–100S. doi: 10.1016/j.jse.2007.07.004. - DOI - PubMed

LinkOut - more resources