Strategy of a cell-derived extracellular matrix for the construction of an osteochondral interlayer

Gao, Chenyuan; Fu, Lei; Yu, Yingjie; Zhang, Xin; Yang, Xiaoping; Cai, Qing

doi:10.1039/d2bm01230h

Cited by 7 publications

(4 citation statements)

References 62 publications

(81 reference statements)

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“…Furthermore, sGAGs and collagen contents were retained after decellularization, which demonstrated that the decellularization process did not greatly affect the ECM composition. In fact, besides sGAGs and collagen, 27,32,39 growth factors such as fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF) have also been shown to be retained after the decellularization treatment. 27 In this work, the electrospun scaffolds fabricated were composed of nanofibers, mimicking the scale of fibers and fibrils present in the native PDL, which are of nano-to microsized order.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Bioactive Nanofibrous Scaffolds Incorporating Decellularized Cell-Derived Extracellular Matrix for Periodontal Tissue Engineering

Santos,

Cordeiro,

Moura

et al. 2024

ACS Appl. Nano Mater.

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Periodontium is a complex structure that supports the teeth, composed of gingiva, cementum, periodontal ligament, and alveolar bone. Destruction of the alveolar bone can occur due to periodontitis, trauma, or following tumor resection. Current reconstructive treatments are based on the use of bone grafts with limited efficacy and predictability, lacking bioactive signals to induce tissue repair and coordinated periodontal regeneration. Thus, alternative strategies are needed to improve clinical outcomes. Cell-derived extracellular matrix (ECM) has been combined with biomaterials to enhance their biofunctionalities for various tissue engineering (TE) applications. In this work, bioactive cell-derived ECM-loaded electrospun polycaprolactone/ chitosan (PCL/CTS) nanofibrous scaffolds were developed by combining polymer solutions with lyophilized decellularized ECM (dECM) derived from human periodontal ligament stem/stromal cells (PDLSCs). This work aimed to fabricate and characterize cell-derived ECM electrospun PCL/CTS scaffolds in terms of morphological, physicochemical, thermal, and mechanical properties and assess their ability to enhance the osteogenic differentiation of PDLSCs, envisaging potential applications in periodontal TE, particularly focused on the regeneration of alveolar bone defects. PDLSCs-derived dECM was characterized regarding morphology, protein expression, DNA removal efficiency, glycosaminoglycans and collagen contents. Osteogenic differentiation of PDLSCs was performed on PCL, PCL/CTS, and PCL/CTS/ECM electrospun scaffolds for 21 days. The obtained results demonstrate that PCL/CTS/ECM scaffolds promoted cell proliferation compared to PCL and PCL/CTS scaffolds while maintaining similar physical and mechanical properties of PCL/CTS scaffolds. PCL/CTS/ECM scaffolds enhanced the osteogenic differentiation of PDLSCs, confirmed by increased alkaline phosphatase activity, calcium deposition, and bone-specific marker gene expression. Moreover, PCL/CTS scaffolds showed higher levels of cell mineralization than did PCL scaffolds. Overall, this work describes the first use of lyophilized cell-derived ECM-loaded electrospun scaffolds for periodontal TE applications, highlighting the potential of this strategy for innovative therapeutic strategies, in particular, for alveolar bone regeneration.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Bioactive Nanofibrous Scaffolds Incorporating Decellularized Cell-Derived Extracellular Matrix for Periodontal Tissue Engineering

Santos,

Cordeiro,

Moura

et al. 2024

ACS Appl. Nano Mater.

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show abstract

“…Furthermore, sGAGs and collagen contents were retained after decellularization, which demonstrated that the decellularization process did not greatly affect the ECM composition. In fact, besides sGAGs and collagen [26,31,37], other growth factors have also been reported to be retained after decellularization treatment [26].…”

Section: Discussionmentioning

confidence: 99%

Cell-derived ECM loaded electrospun Polycaprolactone/Chitosan nanofibrous scaffolds for periodontal regeneration

Santos

Cordeiro

Moura³

et al. 2023

Preprint

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Periodontitis is an inflammatory infection caused by bacterial plaque accumulation that affects the periodontium, a complex structure of different tissues (cementum, periodontal ligament and alveolar bone) that surrounds and supports the teeth. Current treatments lack bioactive signals to induce tissue repair and coordinated regeneration of the periodontium, thus alternative strategies are needed to improve clinical outcomes. Cell-derived extracellular matrix (ECM) has been combined with biomaterials to enhance their biofunctionality for various tissue engineering (TE) applications. In this work, bioactive cell-derived ECM loaded electrospun polycaprolactone/chitosan (PCL/CTS) nanofibrous scaffolds were developed combining polymer solutions with lyophilized decellularized ECM (dECM) derived from human Periodontal Ligament Stem/Stromal Cells (PDLSCs). These work's aims were to fabricate and characterize cell-derived ECM electrospun PCL/CTS scaffolds in terms of morphology, physico-chemical, thermal and mechanical properties and assess their ability to enhance the osteogenic differentiation of PDLSCs, envisaging periodontal TE applications. PDLSCs were cultured and used for dECM production. PDLSCs-derived dECM was characterized regarding morphology, protein expression, DNA removal efficiency, and glycosaminoglycans and collagen contents. Osteogenic differentiation of PDLSCs was performed on PCL, PCL/CTS and PCL/CTS/ECM electrospun scaffolds for 21 days. The obtained results demonstrate that PCL/CTS/ECM scaffolds promoted cell proliferation compared to PCL and PCL/CTS scaffolds, while maintaining similar physical and mechanical properties of PCL/CTS scaffolds. PCL/CTS/ECM scaffolds enhanced the osteogenic differentiation of PDLSCs, confirmed by increased alkaline phosphatase activity, calcium deposition, and bone-specific marker genes expression. Moreover, PCL/CTS scaffolds showed higher levels of cell mineralization than PCL scaffolds. Overall, this work describes the first use of lyophilized cell-derived ECM loaded electrospun scaffolds for periodontal TE applications and highlights its potential as a promising therapeutic strategy for periodontitis treatment.

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“…NPCs can synthesize and deposit their own ECM, allowing scaffolds with specific ECM components and ratios to be fabricated by NPCs [16]. Previous studies have demonstrated the inductive role of cell-derived matrix scaffolds in the differentiation of transplanted stem cells [17,18]. Therefore, matrix microspheres produced by simplex NPCs are ideal scaffolds and have promising applications in treating IVD degeneration.…”

Section: Introductionmentioning

confidence: 99%

Nucleus pulposus cell-derived efficient microcarrier for intervertebral disc tissue engineering

Zhou¹,

Shen²,

Tao³

et al. 2023

Biofabrication

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Adipose-derived stem cells (ADSCs) show great potential for the treatment of intervertebral disc (IVD) degeneration. An ideal carrier is necessary to transplant ADSCs into degenerated IVDs without influencing cell function. Nucleus pulposus cells (NPCs) can synthesize and deposit chondroitin sulfate and type II collagen which are NP-specific extracellular matrix (ECM) and can also regulate the NP-specific differentiation of stem cells. Bioscaffolds fabricated based on the ECM synthesis functions of NPCs have possible roles in cell transplantation and differentiation induction, but it has not been studied. In this study, we first aggregated NPCs into pellets, and then, NPC-derived efficient microcarriers (NPCMs) were fabricated by pellet cultivation under specific conditions and optimized decellularization. Thirdly, we evaluated the microstructure, biochemical composition, biostability and cytotoxicity of the NPCMs. Finally, we investigated the NP-specific differentiation of ADSCs induced by the NPCMs in vitro and NP regeneration induced by the ADSC-loaded NPCMs in a rabbit model. The results indicated that the injectable NPCMs retained maximal ECM and minimal cell nucleic acid after optimized decellularization and had good biostability and no cytotoxicity. The NPCMs also promoted the NP-specific differentiation of ADSCs in vitro. In addition, the results of MRI, X-ray, and the structure and ECM content of NP showed that the ADSCs-loaded NPCMs can partly restored the degenerated NP in vivo. Our injectable NPCMs regenerated the degenerated NP and provide a simplified and efficient strategy for treating IVD degeneration.

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Strategy of a cell-derived extracellular matrix for the construction of an osteochondral interlayer

Abstract: Osteochondral defects pose an enormous challenge due to the lack of the effective repair strategy. To tackle this issue, the importance of the calcified cartilage interlayer (CCL) in modulating osteochondral...

Cited by 7 publications

References 62 publications

Bioactive Nanofibrous Scaffolds Incorporating Decellularized Cell-Derived Extracellular Matrix for Periodontal Tissue Engineering

Bioactive Nanofibrous Scaffolds Incorporating Decellularized Cell-Derived Extracellular Matrix for Periodontal Tissue Engineering

Cell-derived ECM loaded electrospun Polycaprolactone/Chitosan nanofibrous scaffolds for periodontal regeneration

Nucleus pulposus cell-derived efficient microcarrier for intervertebral disc tissue engineering

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