With the discovery of the pivotal role of macrophages in tissue regeneration through shaping the tissue immune microenvironment, various immunomodulatory strategies have been proposed to modify traditional biomaterial...With the discovery of the pivotal role of macrophages in tissue regeneration through shaping the tissue immune microenvironment, various immunomodulatory strategies have been proposed to modify traditional biomaterials. Decellularized extracellular matrix (dECM) has been extensively used in the clinical treatment of tissue injury due to its favorable biocompatibility and similarity to the native tissue environment. However, most reported decellularization protocols may cause damage to the native structure of dECM, which undermines its inherent advantages and potential clinical applications. Here, we introduce a mechanically tunable dECM prepared by optimizing the freeze-thaw cycles. We demonstrated that the alteration in micromechanical properties of dECM resulting from the cyclic freeze-thaw process contributes to distinct macrophage-mediated host immune responses to the materials, which are recently recognized to play a pivotal role in determining the outcome of tissue regeneration. Our sequencing data further revealed that the immunomodulatory effect of dECM was induced via the mechnotrasduction pathways in macrophages. Next, we tested the dECM in a rat skin injury model and found an enhanced micromechanical property of dECM achieved with three freeze-thaw cycles significantly promoted the M2 polarization of macrophages, leading to superior wound healing. These findings suggest that the immunomodulatory property of dECM can be efficiently manipulated by tailoring its inherent micromechanical properties during the decellularization process. Therefore, our mechanics-immunomodulation-based strategy provides new insights into the development of advanced biomaterials for wound healing.展开更多
Infection and poor tissue repair are the key causes of percutaneous implantation failure. However, there is a lackof effective strategies to cope with due to its high requirements of sterilization, soft tissue healing...Infection and poor tissue repair are the key causes of percutaneous implantation failure. However, there is a lackof effective strategies to cope with due to its high requirements of sterilization, soft tissue healing, andosseointegration. In this work, L-arginine (L-Arg) was loaded onto a sulfonated polyetheretherketone (PEEK)surface to solve this issue. Under the infection condition, nitric oxide (NO) and reactive oxygen species (ROS) areproduced through catalyzing L-Arg by inducible nitric oxide synthase (iNOS) and thus play a role in bacteriasterilization. Under the tissue repair condition, L-Arg is catalyzed to ornithine by Arginase-1 (Arg-1), whichpromotes the proliferation and collagen secretion of L929 and rBMSCs. Notably, L-Arg loading samples couldpolarize macrophages to M1 and M2 in infection and tissue repair conditions, respectively. The results in vivoshow that the L-Arg loading samples could enhance infected soft tissue sealing and bone regeneration. Insummary, L-Arg loading sulfonated PEEK could polarize macrophage through metabolic reprogramming,providing multi-functions of antibacterial abilities, soft tissue repair, and bone regeneration, which gives a newidea to design percutaneous implantation materials.展开更多
The authors regret a mistake of funding numbers in the Acknowledgment Section failed to be corrected during proofreading.Below is the corrected funding statement in ACKNOWLEDGMENT SECTION:This work was supported by th...The authors regret a mistake of funding numbers in the Acknowledgment Section failed to be corrected during proofreading.Below is the corrected funding statement in ACKNOWLEDGMENT SECTION:This work was supported by the National Natural Science Foundation of China(NSFC)(Nos.82072415,81772354,81902189),Clinical Innovation Research Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory(2018GZR0201002),Science Technology Project of Guangzhou City(2019ZD15).展开更多
基金supported by National Natural Science Foundation of China(82071167,82001095,81970975,81901055,82201124,82201119)China Postdoctoral Science Foundation(2021TQ0379,2022M713575)+2 种基金Guangdong Basic and Applied Basic Research Foundation(2021A1515110380,2023A1515011963)Health and Medical Research Fund(No.09201466)the Food and Health Bureau,the Government of the HKSAR,China.
文摘With the discovery of the pivotal role of macrophages in tissue regeneration through shaping the tissue immune microenvironment, various immunomodulatory strategies have been proposed to modify traditional biomaterials. Decellularized extracellular matrix (dECM) has been extensively used in the clinical treatment of tissue injury due to its favorable biocompatibility and similarity to the native tissue environment. However, most reported decellularization protocols may cause damage to the native structure of dECM, which undermines its inherent advantages and potential clinical applications. Here, we introduce a mechanically tunable dECM prepared by optimizing the freeze-thaw cycles. We demonstrated that the alteration in micromechanical properties of dECM resulting from the cyclic freeze-thaw process contributes to distinct macrophage-mediated host immune responses to the materials, which are recently recognized to play a pivotal role in determining the outcome of tissue regeneration. Our sequencing data further revealed that the immunomodulatory effect of dECM was induced via the mechnotrasduction pathways in macrophages. Next, we tested the dECM in a rat skin injury model and found an enhanced micromechanical property of dECM achieved with three freeze-thaw cycles significantly promoted the M2 polarization of macrophages, leading to superior wound healing. These findings suggest that the immunomodulatory property of dECM can be efficiently manipulated by tailoring its inherent micromechanical properties during the decellularization process. Therefore, our mechanics-immunomodulation-based strategy provides new insights into the development of advanced biomaterials for wound healing.
基金the National Natural Science Foundation of China(32371397,32000938,U21A20100)The Fundamental Research Funds for The Central Universities(YG2023ZD29)+2 种基金Shenzhen Science and Technology Funding(JCYJ20210324120009026)Laboratory Open Fund of Key Technology and Materials in Minimally Invasive Spine Surgery(2024JZWC-ZDB03,2024JZWC-YBA04)Talent project of Shanghai Tongren Hospital(TRKYRC-xx02)are acknowledged.
文摘Infection and poor tissue repair are the key causes of percutaneous implantation failure. However, there is a lackof effective strategies to cope with due to its high requirements of sterilization, soft tissue healing, andosseointegration. In this work, L-arginine (L-Arg) was loaded onto a sulfonated polyetheretherketone (PEEK)surface to solve this issue. Under the infection condition, nitric oxide (NO) and reactive oxygen species (ROS) areproduced through catalyzing L-Arg by inducible nitric oxide synthase (iNOS) and thus play a role in bacteriasterilization. Under the tissue repair condition, L-Arg is catalyzed to ornithine by Arginase-1 (Arg-1), whichpromotes the proliferation and collagen secretion of L929 and rBMSCs. Notably, L-Arg loading samples couldpolarize macrophages to M1 and M2 in infection and tissue repair conditions, respectively. The results in vivoshow that the L-Arg loading samples could enhance infected soft tissue sealing and bone regeneration. Insummary, L-Arg loading sulfonated PEEK could polarize macrophage through metabolic reprogramming,providing multi-functions of antibacterial abilities, soft tissue repair, and bone regeneration, which gives a newidea to design percutaneous implantation materials.
文摘The authors regret a mistake of funding numbers in the Acknowledgment Section failed to be corrected during proofreading.Below is the corrected funding statement in ACKNOWLEDGMENT SECTION:This work was supported by the National Natural Science Foundation of China(NSFC)(Nos.82072415,81772354,81902189),Clinical Innovation Research Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory(2018GZR0201002),Science Technology Project of Guangzhou City(2019ZD15).
