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Unraveling the potential of 3D bioprinted immunomodulatory materials for regulating macrophage polarization:State-of-the-art in bone and associated tissue regeneration

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Bioactive Materials 2023年第10期28卷 284-310页

作者： sayan deb dutta Tejal V.Patil Keya Ganguly Aayushi Randhawa Ki-Taek Lim Department of Biosystems Engineering Kangwon National UniversityChuncheon24341Republic of Korea Institute of Forest Science Kangwon National UniversityChuncheon24341Republic of Korea Interdisciplinary Program in Smart Agriculture Kangwon National UniversityChuncheon24341Republic of Korea

Macrophage-assisted immunomodulation is an alternative strategy in tissue engineering, wherein the interplay between pro-inflammatory and anti-inflammatory macrophage cells and body cells determines the fate of healing or inflammation. Although several reports have demonstrated that tissue regeneration depends on spatial and temporal regulation of the biophysical or biochemical microenvironment of the biomaterial, the underlying molecular mechanism behind immunomodulation is still under consideration for developing immunomodulatory scaffolds. Currently, most fabricated immunomodulatory platforms reported in the literature show regenerative capabilities of a particular tissue, for example, endogenous tissue (e.g., bone, muscle, heart, kidney, and lungs) or exogenous tissue (e.g., skin and eye). In this review, we briefly introduced the necessity of the 3D immunomodulatory scaffolds and nanomaterials, focusing on material properties and their interaction with macrophages for general readers. This review also provides a comprehensive summary of macrophage origin and taxonomy, their diverse functions, and various signal transduction pathways during biomaterial-macrophage interaction, which is particularly helpful for material scientists and clinicians for developing next-generation immunomodulatory scaffolds. From a clinical standpoint, we briefly discussed the role of 3D biomaterial scaffolds and/or nanomaterial composites for macrophage-assisted tissue engineering with a special focus on bone and associated tissues. Finally, a summary with expert opinion is presented to address the challenges and future necessity of 3D bioprinted immunomodulatory materials for tissue engineering.

关键词： Macrophage Immunomodulation Biomaterials 3D bioprinting Tissue engineering

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Nanocellulose,a versatile platform:From the delivery of active molecules to tissue engineering applications

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Bioactive Materials 2022年第3期7卷 566-589页

作者： Tejal V.Patil Dinesh K.Patel sayan deb dutta Keya Ganguly Tuhin Subhra Santra Ki-Taek Lim Department of Biosystems Engineering Institute of Forest ScienceKangwon National UniversityChuncheon24341Republic of Korea Interdisciplinary Program in Smart Agriculture Kangwon National UniversityChuncheon24341Republic of Korea Deptarment of Engineering Design Indian Institute of TechnologyMadras600036India

Nanocellulose,a biopolymer,has received wide attention from researchers owing to its superior physicochemical properties,such as high mechanical strength,low density,biodegradability,and biocompatibility.Nanocellulose can be extracted from wide range of sources,including plants,bacteria,and algae.Depending on the extraction process and dimensions(diameter and length),they are categorized into three main types:cellulose nanocrystals(CNCs),cellulose nanofibrils(CNFs),and bacterial nanocellulose(BNC).CNCs are a highly crystalline and needle-like structure,whereas CNFs have both amorphous and crystalline regions in their network.BNC is the purest form of nanocellulose.The nanocellulose properties can be tuned by chemical functionalization,which increases its applicability in biomedical applications.This review highlights the fabrication of different surface-modified nanocellulose to deliver active molecules,such as drugs,proteins,and plasmids.Nanocellulose-mediated delivery of active molecules is profoundly affected by its topographical structure and the interaction between the loaded molecules and nanocellulose.The applications of nanocellulose and its composites in tissue engineering have been discussed.Finally,the review is concluded with further opportunities and challenges in nanocellulose-mediated delivery of active molecules.

关键词： Nanocellulose Chemical functionalization Drug delivery Protein delivery Plasmid delivery Tissue engineering

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Understanding cell-extracellular matrix interactions for topology-guided tissue regeneration

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BIOCELL 2023年第4期47卷 789-808页

作者： AAYUSHI RANDHAWA sayan deb dutta KEYA GANGULY TEJAL V.PATIL RACHMI LUTHFIKASARI KI-TAEK LIM Department of Biosystems Engineering Kangwon National UniversityChuncheon24341Korea Interdisciplinary Program in Smart Agriculture Kangwon National UniversityChuncheon24341Korea

Tissues are made up of cells and the extracellular matrix(ECM)which surrounds them.These cells and tissues are actively adaptable to enduring significant stress that occurs in daily life.This astonishing mechanical stress develops due to the interaction between the live cells and the non-living ECM.Cells in the matrix microenvironment can sense the signals and forces produced and initiate a signaling cascade that plays a crucial role in the body’s normal functioning and influences various properties of the native cells,including growth,proliferation,and differentiation.However,the matrix’s characteristic features also impact the repair and regeneration of the damaged tissues.The current study reviewed how the cell-ECM interaction regulates cellular behavior and physicochemical properties.Herein,we have described the response of cells to mechanical stresses,the importance of substrate stiffness and geometry in tissue regeneration,and the development of scaffolds to mimic the nature of native ECM in 3D for tissue engineering applications has also been discussed.Finally,the study summarizes the conclusions and promising prospects based on the cell-ECM interplay.

关键词： ECM Stress Mechanical force Scaffold Mechanotransduction Tissue engineering

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Mesenchymal stem cells,the secretome and biomaterials:Regenerative medicine application

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BIOCELL 2022年第10期46卷 2201-2208页

作者： KI-TAEK LIM TEJAL V.PATIL DINESH KPATEL sayan deb dutta KEYA GANGULY AAYUSHI RANDHAWA Department of Biosystems Engineering Interdisciplinary Program in Smart AgricultureKangwon National UniversityChuncheon341Korea

Mesenchymal stem cells(MSCs)are multipotent cells usually isolated from bone marrow,endometrium,adipose tissues,skin,and dental pulp.MSCs played a crucial role in regenerative therapy and have been introduced as an interdisciplinary field between cell biology and material science.Recently,MSCs have been widely explored for their application in regenerative medicine and COVID-19 treatment.Different approaches to evaluate the future of biomaterials and stem cell properties have been developed.However,misconceptions and ethical issues still exist,such as MSCs being non-angiogenic,anti-apoptotic,and immunoregulatory competencies.Embryonic stem cells isolation primarily requires the consent of donors and can include the killing of fertilized eggs.These issues generate questions related to ethical and moral issues.However,MSCs have gained considerable attention for tissue regeneration owing to their differentiation ability with immunomodulatory effects.They are capable of secreting a broad range of biomolecules such as proteins,nucleic acids,exosomes,microRNAs,and membrane vesicles,collectively known as secretomes.Secretomes are released in response to the surrounding microenvironment.In this article,we briefly address topics related to the therapeutic potential of MSCs as an advanced approach in the field of regenerative medicine and various perspectives.

关键词： Mesenchymal Stem Cells Secretome Biomaterials Regenerative Medicine

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Enhanced osteogenic differentiation of human periodontal ligament stem cells by suberoylanilide hydroxamic acid

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BIOCELL 2020年第3期44卷 389-400页

作者： YUNZE XUAN BIN JIN sayan deb dutta MENGMENG LIU ZAIXIAN SHEN XIWEN LIU YANG KANGJUAN LIM KI-TAEK Department of Stomatology Affiliated Hospital of Yanbian UniversityYanji133000China Department of Immunology and Molecular Microbiology School of Dentistry and Dental Research InstituteSeoul National UniversitySeoul08826South Korea Affiliated Hospital of Yanbian University Yanji133000China Department of Cell Biology and Medical Genetics Yanbian University Medical CollegeYanji133000China Department of Biosystems Engineering Kangwon National UniversityChuncheon24341South Korea

Periodontitis is a type of chronic inflammation in the gingival tissue caused by infectious bacteria colonizing the surface of the teeth,leading to the destruction of tooth-supporting tissues and loss of alveolar bone.Suberoylanilide hydroxamic acid(SAHA),a class of histone deacetylase(HDAC)inhibitor,has the potential to stimulate osteoblast differentiation by acetylating histone proteins,and thus suppressing the expression of adipogenic and chondrogenic genes.However,the effect of SAHA on the differentiation of human periodontal ligament stem cells(hPDLSCs)is yet to be elucidated.Herein,we investigated the effects of SAHA on in vitro proliferation and differentiation of hPDLSCs by MTT assay,Alizarin Red-S,and alkaline phosphatase staining,and real-time PCR.Notably,300 ng/mL SAHA treatment enhanced the proliferation and mineralization of hPDLSCs,indicating their osteogenic potential.Moreover,a significant enhancement of osteogenesis gene markers and proteins was observed.We also demonstrated that ERK is a positive regulator of Runx2 transcription factors during osteoblast differentiation.These results indicate that SAHA may be a useful osteogenic induction agent for periodontal bone regeneration.

关键词： Suberoylanilide hydroxamic acid Histone deacetylase Osteoblast hPDLSCs Alkaline phosphatase Periodontal bone regeneration

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