MSC-derived immunomodulatory extracellular matrix functionalized electrospun fibers for mitigating foreign-body reaction and tendon adhesion

Dong, Lili; Li, Linhao; Song, Yang; Fang, Yihai; Liu, Jinlin; Chen, Peixing; Wang, Sixiang; Wang, Chunli; Xia, Tingting; Liu, Wanqian; Yang, Li

doi:10.1016/j.actbio.2021.04.035

Cited by 45 publications

(30 citation statements)

References 56 publications

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“…Furthermore, in repaired tendons, the pro-inflammatory genes Il-1b and IFNG were both markedly elevated, whereas primed, but not naive ASC EVs reduced the response [ 184 ]. Several studies have demonstrated the effect of immunomodulatory properties of MSCs on reducing the inflammasome in macrophages by modulating macrophage polarization [ 159 , 187 , 188 , 189 , 190 , 191 ]. However, only the study conducted by Dong et al implied the functionalization of randomly oriented electrospun PCL/silk fibroin scaffolds with decellularized ECM derived from hBMSCs (PCL/SF-ECM) ( Table 3 ) [ 159 ].…”

Section: Scaffold Immunoengineering Strategies For Tendon Te Applicationsmentioning

confidence: 99%

“…Several studies have demonstrated the effect of immunomodulatory properties of MSCs on reducing the inflammasome in macrophages by modulating macrophage polarization [ 159 , 187 , 188 , 189 , 190 , 191 ]. However, only the study conducted by Dong et al implied the functionalization of randomly oriented electrospun PCL/silk fibroin scaffolds with decellularized ECM derived from hBMSCs (PCL/SF-ECM) ( Table 3 ) [ 159 ]. In this study, the role of bioactive molecules contained within the PCL/SF-ECM scaffold was assessed on modulating macrophages’ polarization for tendon applications.…”

Section: Scaffold Immunoengineering Strategies For Tendon Te Applicationsmentioning

confidence: 99%

“…In this study, the role of bioactive molecules contained within the PCL/SF-ECM scaffold was assessed on modulating macrophages’ polarization for tendon applications. The fabricated scaffold enhanced M2 macrophage polarization and reduced the expression of multiple cytokines (IL -1β, IL-6, CXCL11, IL-10, IL-1R2 and TGF-β1) in vitro [ 159 ]. TGF-β1 is a profibrotic factor that stimulates fibroblast recruitment and in turn collagen secretion through the Smad3 pathway [ 192 , 193 ].…”

Section: Scaffold Immunoengineering Strategies For Tendon Te Applicationsmentioning

confidence: 99%

“…TGF-β1 is a profibrotic factor that stimulates fibroblast recruitment and in turn collagen secretion through the Smad3 pathway [ 192 , 193 ]. Indeed, probably because of scaffold inhibitory effect on TGF-β1 expression, the results of rat subcutaneous implantation showed a lower FBR, a thinner fibrotic capsule formation, and a higher M2 macrophage phenotype polarization [ 159 ]. Furthermore, Aktas et al, used a rat Achilles segmental defect model to assess the in vivo healing benefits of TNF-α-primed MSCs [ 194 ].…”

Section: Scaffold Immunoengineering Strategies For Tendon Te Applicationsmentioning

confidence: 99%

“…Moreover, YAP and TAZ were founded as binding proteins for Smads, a key transducer of the TGF-β [ 159 , 248 , 249 , 250 ]. Cytoplasmic YAP/TAZ interact with SMAD2/3 through the TAZ coiled-coil domain and participate in Smad2/3 cytoplasmic retaining, even overruling the effects of high levels of TGF-β ligands [ 249 , 250 ].…”

Section: Insights In the Molecular Pathways Regulating The Scaffold’s Mediated Immunomodulationmentioning

confidence: 99%

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Scaffold-Mediated Immunoengineering as Innovative Strategy for Tendon Regeneration

Russo

Khatib

Prencipe

et al. 2022

Cells

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Tendon injuries are at the frontier of innovative approaches to public health concerns and sectoral policy objectives. Indeed, these injuries remain difficult to manage due to tendon’s poor healing ability ascribable to a hypo-cellularity and low vascularity, leading to the formation of a fibrotic tissue affecting its functionality. Tissue engineering represents a promising solution for the regeneration of damaged tendons with the aim to stimulate tissue regeneration or to produce functional implantable biomaterials. However, any technological advancement must take into consideration the role of the immune system in tissue regeneration and the potential of biomaterial scaffolds to control the immune signaling, creating a pro-regenerative environment. In this context, immunoengineering has emerged as a new discipline, developing innovative strategies for tendon injuries. It aims at designing scaffolds, in combination with engineered bioactive molecules and/or stem cells, able to modulate the interaction between the transplanted biomaterial-scaffold and the host tissue allowing a pro-regenerative immune response, therefore hindering fibrosis occurrence at the injury site and guiding tendon regeneration. Thus, this review is aimed at giving an overview on the role exerted from different tissue engineering actors in leading immunoregeneration by crosstalking with stem and immune cells to generate new paradigms in designing regenerative medicine approaches for tendon injuries.

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Section: Scaffold Immunoengineering Strategies For Tendon Te Applicationsmentioning

confidence: 99%

Section: Scaffold Immunoengineering Strategies For Tendon Te Applicationsmentioning

confidence: 99%

Section: Scaffold Immunoengineering Strategies For Tendon Te Applicationsmentioning

confidence: 99%

Section: Scaffold Immunoengineering Strategies For Tendon Te Applicationsmentioning

confidence: 99%

Section: Insights In the Molecular Pathways Regulating The Scaffold’s Mediated Immunomodulationmentioning

confidence: 99%

See 3 more Smart Citations

Scaffold-Mediated Immunoengineering as Innovative Strategy for Tendon Regeneration

Russo

Khatib

Prencipe

et al. 2022

Cells

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Acellularized Uvea Hydrogel as Novel Injectable Platform for Cell‐Based Delivering Treatment of Retinal Degeneration and Optimizing Retinal Organoids Inducible System

Liu

Chen

et al. 2022

Adv Healthcare Materials

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Replenishing the retina with retinal pigment epithelial (RPE) cells derived from pluripotent stem cells (PSCs) has great promise for treating retinal degenerative diseases, but it is limited by poor cell survival and integration in vivo. Herein, porcine acellular sclera and uvea extracellular matrix (ECM) and their counterpart hydrogels are developed, and their effects on the biological behavior of human induced pluripotent stem cell (hiPSC)‐derived RPE cells (hiPSC‐RPE) and embryoid body (hiPSC‐EB) differentiation are investigated. Both acellular ECM hydrogels have excellent biocompatibility and suitable biodegradability without evoking an obvious immune response. Most importantly, the decellularized uvea hydrogel‐delivered cells’ injection remarkably promotes the hiPSC‐RPE cells’ survival and integration in the subretinal space, rescues the photoreceptor cells’ death and retinal gliosis, and restores vision in rats with retinal degeneration for a long duration. In addition, medium supplementation with decellularized uvea peptides promotes hiPSC‐EBs onset morphogenesis and neural/retinal differentiation, forming layered retinal organoids. This study demonstrates that ECM hydrogel‐delivered hiPSC‐RPE cells’ injection may be a useful approach for treating retinal degeneration disease, combined with an optimized retinal seeding cells’ induction program, which has potential for clinical application.

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Silk Fibroin and Sericin Differentially Potentiate the Paracrine and Regenerative Functions of Stem Cells Through Multiomics Analysis

et al. 2023

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emerging as a potential alternative to these problems. The tissue engineering triad involves the effective integration of cells, scaffolds, and signals for the development of biological substitutes to restore, maintain, and replace injured tissues and organs. [2] The scaffold plays a substantial role in the field of tissue engineering, primarily by providing physical support (structures and substrates) for cells to attach and grow, subsequently resulting in tissue formation. [3] A variety of natural and synthetic biomaterials have been explored to develop tissue-engineered scaffolds. By incorporating exogenous growthstimulating signals, such as growth factors or small molecules, scaffolds can provide specific bioactivities, that is, biochemical signals required for cellular behaviors and tissue regeneration. [4] As biomaterials are essentially comprised of chemical molecules, they are capable of supplying inherent biochemical signals to guide and influence cells. For example, cells residing in tissue-engineered scaffolds can establish cell-biomaterial communication networks partially through biochemical signaling. The degradation products of various biodegradable biomaterials after implantation in vivo also provide specific biochemical signals to the cells in and around the Silk fibroin (SF) and sericin (SS), the two major proteins of silk, are attractive biomaterials with great potential in tissue engineering and regenerative medicine. However, their biochemical interactions with stem cells remain unclear. In this study, multiomics are employed to obtain a global view of the cellular processes and pathways of mesenchymal stem cells (MSCs) triggered by SF and SS to discern cell-biomaterial interactions at an in-depth, high-throughput molecular level. Integrated RNA sequencing and proteomic analysis confirm that SF and SS initiate widespread but distinct cellular responses and potentiate the paracrine functions of MSCs that regulate extracellular matrix deposition, angiogenesis, and immunomodulation through differentially activating the integrin/PI3K/Akt and glycolysis signaling pathways. These paracrine signals of MSCs stimulated by SF and SS effectively improve skin regeneration by regulating the behavior of multiple resident cells (fibroblasts, endothelial cells, and macrophages) in the skin wound microenvironment. Compared to SS, SF exhibits better immunomodulatory effects in vitro and in vivo, indicating its greater potential as a carrier material of MSCs for skin regeneration. This study provides comprehensive and reliable insights into the cellular interactions with SF and SS, enabling the future development of silk-based therapeutics for tissue engineering and stem cell therapy.

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MSC-derived immunomodulatory extracellular matrix functionalized electrospun fibers for mitigating foreign-body reaction and tendon adhesion

Cited by 45 publications

References 56 publications

Scaffold-Mediated Immunoengineering as Innovative Strategy for Tendon Regeneration

Scaffold-Mediated Immunoengineering as Innovative Strategy for Tendon Regeneration

Acellularized Uvea Hydrogel as Novel Injectable Platform for Cell‐Based Delivering Treatment of Retinal Degeneration and Optimizing Retinal Organoids Inducible System

Silk Fibroin and Sericin Differentially Potentiate the Paracrine and Regenerative Functions of Stem Cells Through Multiomics Analysis

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