Pegylated insulin‐like growth factor‐1 biotherapeutic delivery promotes rotator cuff regeneration in a rat model

Prabhath, Anupama; Vernekar, Varadraj N.; Esdaille, Caldon Jayson; Eisenberg, Ellen; Lebaschi, Amir; Badon, Mary; Seyedsalehi, Amir; Dzidotor, Godwin K.; Tang, Xiaoyan; Dyment, Nathaniel A.; Thomopoulos, Stavros; Kumbar, Sangamesh G.; Deymier, Alix C.; Weber, Eckhard; Laurencin, Cato T.

doi:10.1002/jbm.a.37378

Cited by 13 publications

(5 citation statements)

References 51 publications

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“…8e). The recent study reported IGF1 from macrophages could promote muscle regeneration and IGF1 could heal tendon lesion [53][54][55] . MP3 may inhibit fibrosis by IGF1 through MAPK signaling pathway to promote tendon healing.…”

Section: Deciphering the Intricate Interplay Among Multiple Cell Line...mentioning

confidence: 99%

Multi-omics analysis of human tendon adhesion reveals ACKR1 migrates macrophages involve in endogenous regeneration

Liu,

Li,

Liu

et al. 2023

Preprint

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Tendon adhesion is a common complication after tendon injury with the development of accumulated fibrotic tissues without effective anti-fibrotic therapies, resulting in severe disability. Macrophages are widely recognized as a fibrotic trigger during peritendinous adhesion formation. However, different clusters of macrophages have various functions and receives multiple regulation, which are both still unknown. In our current study, multi-omics analysis including scRNA-seq and proteomics were performed on both human and mouse tendon adhesion tissue at different stages after tendon injury. The transcriptomes of over 74,000 human single cells were profiled. As results, we found that SPP1+ macrophages, RGCC+ endothelial cells, ACKR1+ endothelial cells and ADAM12+ fibroblasts participated in tendon adhesion formation. Interestingly, despite of specific fibrotic clusters in tendon adhesion, FOLR2+ macrophages were identified as the antifibrotic cluster identified by in vitro experiments using human cells. Furthermore, ACKR1 were verified to regulate FOLR2+ macrophages migration in the injured peritendinous site by transplantation of bone marrow from Lysm-cre::R26R-Tdtomato mice to lethally irradiated Ackr1−/− mice (ACKR1−/− chimeras; deficient in ACKR1) and control mice (WT chimeras). By comparing with WT chimeras, the decline of FOLR2+ macrophages were also significantly observed, indicating that ACKR1 was specifically involved in FOLR2+ macrophages migration. Taken together, our study not only characterized the fibrosis microenvironment landscape of tendon adhesion by multi-omics analysis, but also uncovered the novel antifibrotic cluster of macrophages and their origin. These results provide potential therapeutic targets against human tendon adhesion.

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Section: Deciphering the Intricate Interplay Among Multiple Cell Line...mentioning

confidence: 99%

Multi-omics analysis of human tendon adhesion reveals ACKR1 migrates macrophages involve in endogenous regeneration

Liu,

Li,

Liu

et al. 2023

Preprint

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“…Insulin-like growth factor 1 (IGF-1) facilitates the production of aggregation proteins and reduces their catabolism, but unmodified IGF-1 has a short half-life and can easily diffuse outside of the joint, leading to unfavorable side effects (Tyler, 1989;Shi et al, 2020;Prabhath et al, 2022). Sustained and local delivery of IGF-1 to cartilage can come true by combining the heparin-binding epidermal growth factorlike growth factor (HB-EGF) with IGF-1 to generate heparinbinding insulin-like growth factor 1 (HB-IGF-1) (Mujeeb et al, 2013;Sarkar et al, 2019;Zhang X. et al, 2021).…”

Section: Growth Factorsmentioning

confidence: 99%

Research progress of self-assembling peptide hydrogels in repairing cartilage defects

Wang

Yang

et al. 2022

Front. Mater.

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Due to the lack of blood vessels, nerves and lymphatic vessels, the capacity of articular cartilage to heal is extremely limited. Once damaged, it is urgent for articular cartilage to repair the injury. In recent years, there has been an increase in cartilage tissue engineering studies. Self-assembling peptide hydrogel as a kind of hydrogels composed of peptides and water is widely used in cartilage tissue engineering. Under noncovalent interactions such as electrostatic interaction, hydrophobic interaction, hydrogen bonding and pi-pi stacking force, peptides self-assemble into three-dimensional (3D) structures that mimic the natural extracellular matrix and allow cells to grow, proliferate and differentiate. Because SAPHs have excellent biocompatibility and biodegradability, variable mechanical properties, low immunogenicity, injectability, and the ability to load cells and bioactive substances, many researchers utilized them to promote the repair and regeneration of articular cartilage after damage. Therefore, the purpose of this review is to sum up the composition, injury characteristics, and treatments of articular cartilage, as well as the action of SAPHs in repairing articular cartilage damage.

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“…It is known to regulate both anabolic and catabolic pathways in skeletal muscle [ 15 ], aid ageing processes (together with GH), and act synergistically with PDGF-BB in cell cultures aimed at tendon tissue engineering [ 16 ]. Moreover, several approaches including IGF-1 in tendon healing have been successful [ 17 ], i.e., reaching earlier functional recovery of a rat’s Achilles tendon [ 18 ] or a rat’s rotator cuff tendon [ 19 ], resulting in higher cell proliferation and collagen content in IGF-1-treated equine flexor tendinitis [ 20 ] or increased tendon biomechanics in rabbit patellar tendons in combination with TGF-β [ 21 ]. In addition, activation of the IGF1R (receptor for IGF-1) and MAPK signaling by a phytoestrogen has recently been reported to support tendon healing in a rat Achilles tendon model [ 22 ], demonstrating the positive effect of these signaling cascades that are also activated through IGF-1 binding to IGF1R.…”

Section: Introductionmentioning

confidence: 99%

Bioactive and Elastic Emulsion Electrospun DegraPol Tubes Delivering IGF-1 for Tendon Rupture Repair

Rieber

Meier-Bürgisser

Miescher

et al. 2023

IJMS

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Tendon injuries can result in two major drawbacks. Adhesions to the surrounding tissue may limit the range of motion, while fibrovascular scar formation can lead to poor biomechanical outcomes. Prosthetic devices may help to mitigate those problems. Emulsion electrospinning was used to develop a novel three-layer tube based on the polymer DegraPol (DP), with incorporated insulin-like growth factor-1 (IGF-1) in the middle layer. Scanning electron microscopy was utilized to assess the fiber diameter in IGF-1 containing pure DP meshes. Further characterization was performed with Fourier Transformed Infrared Spectroscopy, Differential Scanning Calorimetry, and water contact angle, as well as through the assessment of mechanical properties and release kinetics from ELISA, and the bioactivity of IGF-1 by qPCR of collagen I, ki67, and tenomodulin in rabbit Achilles tenocytes. The IGF-1-containing tubes exhibited a sustained release of the growth factor up to 4 days and showed bioactivity by significantly upregulated ki67 and tenomodulin gene expression. Moreover, they proved to be mechanically superior to pure DP tubes (significantly higher fracture strain, failure stress, and elastic modulus). The novel three-layer tubes intended to be applied over conventionally sutured tendons after a rupture may help accelerate the healing process. The release of IGF-1 stimulates proliferation and matrix synthesis of cells at the repair site. In addition, adhesion formation to surrounding tissue can be reduced due to the physical barrier.

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Pegylated insulin‐like growth factor‐1 biotherapeutic delivery promotes rotator cuff regeneration in a rat model

Cited by 13 publications

References 51 publications

Multi-omics analysis of human tendon adhesion reveals ACKR1 migrates macrophages involve in endogenous regeneration

Multi-omics analysis of human tendon adhesion reveals ACKR1 migrates macrophages involve in endogenous regeneration

Research progress of self-assembling peptide hydrogels in repairing cartilage defects

Bioactive and Elastic Emulsion Electrospun DegraPol Tubes Delivering IGF-1 for Tendon Rupture Repair

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