Neonatal Enthesis Healing Involves Noninflammatory Acellular Scar Formation through Extracellular Matrix Secretion by Resident Cells

Vinestock, Ron Carmel; Felsenthal, Neta; Assaraf, Eran; Katz, Eldad; Rubin, Sarah; Heinemann-Yerushalmi, Lia; Krief, Sharon; Dezorella, Nili; Levin-Zaidman, Smadar; Tsoory, Michael; Thomopoulos, Stavros; Zelzer, Elazar

doi:10.1016/j.ajpath.2022.05.008

Cited by 2 publications

(3 citation statements)

References 71 publications

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“…As the cells deposit ECM, a functional gradient forms at the tendon-to-bone insertion [ 6 ], and at the same time, cellular density decreases [ 5 ]. Interfacial tissue healing during enthesis development has recently shown that the tendon-bone enthesis also has innate regenerative properties which are not modeled in adult animals [ 7 – 9 ].…”

Section: Cues From Interface Development To Guide Regenerative Approa...mentioning

confidence: 99%

“…Post-injury in the neonatal enthesis, the injured tissue is hypocellular and avascular [ 9 ]. In tendon, Grinstein et al demonstrated that tendon cells shift from rates of high to low proliferation during postnatal growth in mice, and expression of genes associated with tendon transcription factors and ECM decreases with age [ 10 ].…”

Section: Cues From Interface Development To Guide Regenerative Approa...mentioning

confidence: 99%

“…While inflammation is a key response to injury, chronic inflammation and accumulated fibrotic ECM can hinder the ability of interfacial tissue to regenerate. Clues from neonatal healing may provide insights of the regenerative potential of remodeling or maintenance of the native ECM by tissue resident cells, as a recent study by Vinestock et al has shown that neonatal enthesis injury leads to generation of an acellular and low-inflammatory scar driven primarily by resident cells [ 9 ]. The intricate crosstalk between cells and their nascent ECM may influence the inflammatory response involved in tissue remodeling.…”

Section: Contributions Of the Local Ecm On Interfacial Development An...mentioning

confidence: 99%

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Interfacial Tissue Regeneration with Bone

Steltzer,

Abraham,

Killian

2024

Curr Osteoporos Rep

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Purpose of Review Interfacial tissue exists throughout the body at cartilage-to-bone (osteochondral interface) and tendon-to-bone (enthesis) interfaces. Healing of interfacial tissues is a current challenge in regenerative approaches because the interface plays a critical role in stabilizing and distributing the mechanical stress between soft tissues (e.g., cartilage and tendon) and bone. The purpose of this review is to identify new directions in the field of interfacial tissue development and physiology that can guide future regenerative strategies for improving post-injury healing. Recent Findings Cues from interfacial tissue development may guide regeneration including biological cues such as cell phenotype and growth factor signaling; structural cues such as extracellular matrix (ECM) deposition, ECM, and cell alignment; and mechanical cues such as compression, tension, shear, and the stiffness of the cellular microenvironment. Summary In this review, we explore new discoveries in the field of interfacial biology related to ECM remodeling, cellular metabolism, and fate. Based on emergent findings across multiple disciplines, we lay out a framework for future innovations in the design of engineered strategies for interface regeneration. Many of the key mechanisms essential for interfacial tissue development and adaptation have high potential for improving outcomes in the clinic.

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Section: Cues From Interface Development To Guide Regenerative Approa...mentioning

confidence: 99%

Section: Cues From Interface Development To Guide Regenerative Approa...mentioning

confidence: 99%

Section: Contributions Of the Local Ecm On Interfacial Development An...mentioning

confidence: 99%

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Interfacial Tissue Regeneration with Bone

Steltzer,

Abraham,

Killian

2024

Curr Osteoporos Rep

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Revealing the Auxetic Behavior of Biomimetic Multi-material and Region-specific Nanofibrous Scaffolds via Synchrotron Multiscale Digital Volume Correlation: Innovative Building Blocks for the Enthesis Regeneration

Sensini,

Giacomini,

Stamati

et al. 2024

Preprint

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Enthesis lesions are one of the prevalent causes of injuries in the tendon tissue. The gradient of mineralization, extracellular matrix organization and auxetic mechanical properties, make enthesis regeneration challenging. Innovative electrospun fascicle-inspired nanofibrous poly(L-lactic)acid/collagen type I blend scaffolds were developed. Specifically, a mineralized fibrocartilage-inspired region (with/without nano-mineralization with hydroxyapatite), where random and aligned nanofibers coexist, is connected to a tendon-like region made of aligned nanofibers, through a conical non-mineralized fibrocartilage-inspired junction. Scanning electron microscopy and synchrotron nano-tomography show the morphological biomimicry of scaffolds with the natural tendon fascicles. Human mesenchymal stromal cells spheroids cultures confirm a balanced expression of both tendon, cartilage and bone markers on the non- mineralized scaffolds compared with the mineralized ones. Mechanical tests, at different physiological strain-rates, reveal a biomimetic mechanical behavior of scaffolds and the ability of junctions to tune the mechanics of their surrounding sites. Multiscale synchrotron in situ tensile tests, coupled with Digital Volume Correlation, elucidate the full-field strain distribution of scaffolds from the structural down to the nanofiber level, highlighting the auxetic mechanical behavior of junctions typical of the natural enthesis. The findings and cutting-edge investigations of our study suggest the suitability of these enthesis-inspired fascicles as innovative scaffolds for enhanced enthesis regeneration.

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Neonatal Enthesis Healing Involves Noninflammatory Acellular Scar Formation through Extracellular Matrix Secretion by Resident Cells

Cited by 2 publications

References 71 publications

Interfacial Tissue Regeneration with Bone

Interfacial Tissue Regeneration with Bone

Revealing the Auxetic Behavior of Biomimetic Multi-material and Region-specific Nanofibrous Scaffolds via Synchrotron Multiscale Digital Volume Correlation: Innovative Building Blocks for the Enthesis Regeneration

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