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      3D-printed hydrogel particles containing PRP laden with TDSCs promote tendon repair in a rat model of tendinopathy

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          Abstract

          Long-term chronic inflammation after Achilles tendon injury is critical for tendinopathy. Platelet-rich plasma (PRP) injection, which is a common method for treating tendinopathy, has positive effects on tendon repair. In addition, tendon-derived stem cells (TDSCs), which are stem cells located in tendons, play a major role in maintaining tissue homeostasis and postinjury repair. In this study, injectable gelatine methacryloyl (GelMA) microparticles containing PRP laden with TDSCs (PRP–TDSC–GM) were prepared by a projection-based 3D bioprinting technique. Our results showed that PRP–TDSC–GM could promote tendon differentiation in TDSCs and reduce the inflammatory response by downregulating the PI3K–AKT pathway, thus promoting the structural and functional repair of tendons in vivo.

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          Supplementary Information

          The online version contains supplementary material available at 10.1186/s12951-023-01892-5.

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          Synthesis, properties, and biomedical applications of gelatin methacryloyl (GelMA) hydrogels.

          Kan Yue, Grissel Trujillo-de Santiago, Mario Moisés Alvarez … (2015)
          Gelatin methacryloyl (GelMA) hydrogels have been widely used for various biomedical applications due to their suitable biological properties and tunable physical characteristics. GelMA hydrogels closely resemble some essential properties of native extracellular matrix (ECM) due to the presence of cell-attaching and matrix metalloproteinase responsive peptide motifs, which allow cells to proliferate and spread in GelMA-based scaffolds. GelMA is also versatile from a processing perspective. It crosslinks when exposed to light irradiation to form hydrogels with tunable mechanical properties. It can also be microfabricated using different methodologies including micromolding, photomasking, bioprinting, self-assembly, and microfluidic techniques to generate constructs with controlled architectures. Hybrid hydrogel systems can also be formed by mixing GelMA with nanoparticles such as carbon nanotubes and graphene oxide, and other polymers to form networks with desired combined properties and characteristics for specific biological applications. Recent research has demonstrated the proficiency of GelMA-based hydrogels in a wide range of tissue engineering applications including engineering of bone, cartilage, cardiac, and vascular tissues, among others. Other applications of GelMA hydrogels, besides tissue engineering, include fundamental cell research, cell signaling, drug and gene delivery, and bio-sensing.
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            Identification of tendon stem/progenitor cells and the role of the extracellular matrix in their niche.

            Yanming Bi, Driss Ehirchiou, Tina Kilts … (2007)
            The repair of injured tendons remains a great challenge, largely owing to a lack of in-depth characterization of tendon cells and their precursors. We show that human and mouse tendons harbor a unique cell population, termed tendon stem/progenitor cells (TSPCs), that has universal stem cell characteristics such as clonogenicity, multipotency and self-renewal capacity. The isolated TSPCs could regenerate tendon-like tissues after extended expansion in vitro and transplantation in vivo. Moreover, we show that TSPCs reside within a unique niche predominantly comprised of an extracellular matrix, and we identify biglycan (Bgn) and fibromodulin (Fmod) as two critical components that organize this niche. Depletion of Bgn and Fmod affects the differentiation of TSPCs by modulating bone morphogenetic protein signaling and impairs tendon formation in vivo. Our results, while offering new insights into the biology of tendon cells, may assist in future strategies to treat tendon diseases.
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              Akt Signaling Pathway in Macrophage Activation and M1/M2 Polarization.

              Eleni Vergadi, Eleftheria Ieronymaki, Konstantina Lyroni … (2017)
              Macrophages become activated initiating innate immune responses. Depending on the signals, macrophages obtain an array of activation phenotypes, described by the broad terms of M1 or M2 phenotype. The PI3K/Akt/mTOR pathway mediates signals from multiple receptors including insulin receptors, pathogen-associated molecular pattern receptors, cytokine receptors, adipokine receptors, and hormones. As a result, the Akt pathway converges inflammatory and metabolic signals to regulate macrophage responses modulating their activation phenotype. Akt is a family of three serine-threonine kinases, Akt1, Akt2, and Akt3. Generation of mice lacking individual Akt, PI3K, or mTOR isoforms and utilization of RNA interference technology have revealed that Akt signaling pathway components have distinct and isoform-specific roles in macrophage biology and inflammatory disease regulation, by controlling inflammatory cytokines, miRNAs, and functions including phagocytosis, autophagy, and cell metabolism. Herein, we review the current knowledge on the role of the Akt signaling pathway in macrophages, focusing on M1/M2 polarization and highlighting Akt isoform-specific functions.
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                Author and article information

                Contributors
                Xiaohua Yu: xiaohua.yu@zju.edu.cn
                Guangyao Jiang: 11718243@zju.edu.cn
                An Liu: la@zju.edu.cn
                Journal
                Journal ID (nlm-ta): J Nanobiotechnology
                Journal ID (iso-abbrev): J Nanobiotechnology
                Title: Journal of Nanobiotechnology
                Publisher: BioMed Central (London )
                ISSN (Electronic): 1477-3155
                Publication date (Electronic): 3 June 2023
                Publication date PMC-release: 3 June 2023
                Publication date Collection: 2023
                Volume: 21
                Electronic Location Identifier: 177
                Affiliations
                [1 ]GRID grid.13402.34, ISNI 0000 0004 1759 700X, Department of Orthopedic Surgery, The Second Affiliated Hospital, , Zhejiang University School of Medicine, ; Hangzhou City, Zhejiang Province PR China
                [2 ]GRID grid.13402.34, ISNI 0000 0004 1759 700X, Orthopedics Research Institute of Zhejiang University, ; Hangzhou City, Zhejiang Province PR China
                [3 ]GRID grid.412465.0, Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, ; Hangzhou City, Zhejiang Province PR China
                [4 ]Clinical Research Center of Motor System Disease of Zhejiang Province, Hangzhou, PR China
                [5 ]State Key Laboratory of Fluid Power and Mechatronic Systems, School of Mechanical Engineering, Hangzhou, Zhejiang PR China
                Article
                Publisher ID: 1892
                DOI: 10.1186/s12951-023-01892-5
                PMC ID: 10239155
                PubMed ID: 37268942
                SO-VID: 4f74245b-3f07-4f3c-9491-08a4e12d9acf
                Copyright © © The Author(s) 2023
                License:

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                Date received : 10 December 2022
                Date accepted : 11 April 2023
                Funding
                Funded by: National Natural Science Foundation of China
                Award ID: 81902279
                Award Recipient :
                Funded by: Young Scientist Fund of the National Natural Science Foundation of China
                Award ID: 82001458
                Award Recipient :
                Categories
                Subject: Research
                Custom metadata
                issue-copyright-statement © BioMed Central Ltd., part of Springer Nature 2023

                ScienceOpen disciplines: Biotechnology
                Keywords: hydrogel,tdscs,tendinopathy,inflammation,pi3k-akt pathway
                Data availability:
                ScienceOpen disciplines: Biotechnology
                Keywords: hydrogel, tdscs, tendinopathy, inflammation, pi3k-akt pathway

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