Implementation of a stratified approach and gene immobilization to enhance the osseointegration of a silk-based ligament graft

Fan, Jiabing; Sun, Liguo; Chen, Xiaonan; Qu, Ling; Li, Hongguo; Liu, Xincheng; Zhang, Yushen; Cheng, Pengzhen; Fan, Hongbin

doi:10.1039/c7tb01579h

Cited by 13 publications

(8 citation statements)

References 42 publications

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“…SF scaffolds modified or coated with HAp nanoparticles could stimulate the proliferation, differentiation, and osteogenesis of bone marrow mesenchymal stem cells (BMSCs), to be further applied as ligament grafts in bone-ligament defects repair and ACL reconstruction [23,68]. SF has been successfully applied for ACL TE approaches [20,25,69], however, the osteointegration ability of the SF-based scaffolds is usually ensured by incorporating inorganic components that subsequently accelerate bone tunnel regeneration [22].…”

Section: Cell Viability Proliferation and Morphological Profilementioning

confidence: 99%

Bioinspired Silk Fibroin-Based Composite Grafts as Bone Tunnel Fillers for Anterior Cruciate Ligament Reconstruction

et al. 2022

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Anterior cruciate ligament (ACL) replacement is still a big challenge in orthopedics due to the need to develop bioinspired implants that can mimic the complexity of bone-ligament interface. In this study, we propose biomimetic composite tubular grafts (CTGs) made of horseradish peroxidase (HRP)-cross-linked silk fibroin (SF) hydrogels containing ZnSr-doped β-tricalcium phosphate (ZnSr-β-TCP) particles, as promising bone tunnel fillers to be used in ACL grafts (ACLGs) implantation. For comparative purposes, plain HRP-cross-linked SF hydrogels (PTGs) were fabricated. Sonication and freeze-drying methodologies capable of inducing crystalline β-sheet conformation were carried out to produce both the CTGs and PTGs. A homogeneous microstructure was achieved from microporous to nanoporous scales. The mechanical properties were dependent on the inorganic powder’s incorporation, with a superior tensile modulus observed on the CTGs (12.05 ± 1.03 MPa) as compared to the PTGs (5.30 ± 0.93 MPa). The CTGs presented adequate swelling properties to fill the space in the bone structure after bone tunnel enlargement and provide a stable degradation profile under low concentration of protease XIV. The in vitro studies revealed that SaOs-2 cells adhered, proliferated and remained viable when cultured into the CTGs. In addition, the bioactive CTGs supported the osteogenic activity of cells in terms of alkaline phosphatase (ALP) production, activity, and relative gene expression of osteogenic-related markers. Therefore, this study is the first evidence that the developed CTGs hold adequate structural, chemical, and biological properties to be used as bone tunnel fillers capable of connecting to the ACL tissue while stimulating bone tissue regeneration for a faster osteointegration.

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Section: Cell Viability Proliferation and Morphological Profilementioning

confidence: 99%

Bioinspired Silk Fibroin-Based Composite Grafts as Bone Tunnel Fillers for Anterior Cruciate Ligament Reconstruction

et al. 2022

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“…To attract stem cells into the scaffold, chemokines can be applied [ 65 ]. To simulate the insertion stratified structure, a triphasic silk-based graft was established with different cell types [ 42 , 122 ], with specific induction treatment being applied to different parts of the graft. Decellularized allogenic scaffold is more similar to the original environment and enables easy seeding of cells [ 107 ].…”

Section: Prospectsmentioning

confidence: 99%

Application of Stem Cell Therapy for ACL Graft Regeneration

Wang

Zhang

et al. 2021

Stem Cells International

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Graft regeneration after anterior cruciate ligament (ACL) reconstruction surgery is a complex three-stage process, which usually takes a long duration and often results in fibrous scar tissue formation that exerts a detrimental impact on the patients’ prognosis. Hence, as a regeneration technique, stem cell transplantation has attracted increasing attention. Several different stem cell types have been utilized in animal experiments, and almost all of these have shown good capacity in improving tendon-bone regeneration. Various differentiation inducers have been widely applied together with stem cells to enhance specific lineage differentiation, such as recombinant gene transfection, growth factors, and biomaterials. Among the various different types of stem cells, bone marrow-derived mesenchymal stem cells (BMSCs) have been investigated the most, while ligament stem progenitor cells (LDSCs) have demonstrated the best potential in generating tendon/ligament lineage cells. In the clinic, 4 relevant completed trials have been reported, but only one trial with BMSCs showed improved outcomes, while 5 relevant trials are still in progress. This review describes the process of ACL graft regeneration after implantation and summarizes the current application of stem cells from bench to bedside, as well as discusses future perspectives in this field.

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“…When cell‐seeded scaffolds were rolled up and implanted into rabbits, regenerated ligament‐like tissues were formed in the ligament region of the scaffold, and bone formation was almost complete according to imaging results in the bone region 24 weeks after implantation (Figure 2i–l). In a later study, lentiviral vectors‐encoded TGF‐ β 3 and bone morphogenetic protein‐2 (BMP‐2) were immobilised to fibrocartilage and bone regions of the triphasic silk‐based scaffolds, respectively [28]. MSCs seeded on the same scaffolds can be differentiated into osteoblasts, chondrocytes and fibroblasts in different regions.…”

Section: Biofabrication Of Stratified Scaffolds With Layer‐specific M...mentioning

confidence: 99%

Advanced biofabrication strategies for biomimetic composite scaffolds to regenerate ligament‐bone interface

Jiang

Mao

Xiao

et al. 2021

Biosurface and Biotribology

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The natural ligament-bone interface features gradient changes in matrix composition, architecture and cell phenotype, which play critical roles in reliable ligament fixation and smooth loading transfer. Mimicking such organisations in artificial composite tissueengineering scaffolds is important for realising functional fixation between ligament implants and host bones. Here, the authors aim to provide a comprehensive review on the latest strategies to fabricate biomimetic composite scaffolds for the regeneration of ligament-to-bone interface. The biomimetic composite scaffolds are divided into stratified and gradient scaffolds, which are characterised as layer-specific and continuous changes, respectively, in scaffold materials and/or microstructures. Biofabrication strategies for different types of composite scaffolds are summarised. The effects of material/structural changes on cellular morphology, cell differentiation, in vivo osteointegration and multitissue interface regeneration are highlighted. Finally, the potential challenges and future perspectives in engineering biomimetic composite scaffolds for ligament-bone interface regeneration are discussed.

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Implementation of a stratified approach and gene immobilization to enhance the osseointegration of a silk-based ligament graft

Abstract: Integration of a stratified approach and gene immobilization promotes silk-based ACL interface formation, expanding the therapeutic potential of a silk-based ligament graft.

Cited by 13 publications

References 42 publications

Bioinspired Silk Fibroin-Based Composite Grafts as Bone Tunnel Fillers for Anterior Cruciate Ligament Reconstruction

Bioinspired Silk Fibroin-Based Composite Grafts as Bone Tunnel Fillers for Anterior Cruciate Ligament Reconstruction

Application of Stem Cell Therapy for ACL Graft Regeneration

Advanced biofabrication strategies for biomimetic composite scaffolds to regenerate ligament‐bone interface

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