3D Printed Poly(ε-Caprolactone)/Meniscus Extracellular Matrix Composite Scaffold Functionalized With Kartogenin-Releasing PLGA Microspheres for Meniscus Tissue Engineering

Published on Apr 30, 2021in Frontiers in Bioengineering and Biotechnology3.644
· DOI :10.3389/FBIOE.2021.662381
Hao Li98
Estimated H-index: 98
(NKU: Nankai University),
Hao Li1
Estimated H-index: 1
+ 10 AuthorsQuanyi Guo27
Estimated H-index: 27
Meniscus tissue engineering (MTE) aims to fabricate ideal scaffolds to stimulate the microenvironment for recreating the damaged meniscal tissue. Indeed, favorable mechanical properties, suitable biocompatibility, and inherent chondrogenic capability are crucial in MTE. In this study, we present a composite scaffold by 3D printing a poly(e-caprolactone) (PCL) scaffold as backbone, followed by injection with the meniscus extracellular matrix (MECM), and modification with kartogenin (KGN)-loaded poly(lactic-co-glycolic) acid (PLGA) microsphere (μS), which serves as a drug delivery system. Therefore, we propose a plan to improve meniscus regeneration via KGN released from the 3D porous PCL/MECM scaffold. The final results showed that the hydrophilicity and bioactivity of the resulting PCL/MECM scaffold were remarkably enhanced. In vitro synovium-derived mesenchymal stem cells (SMSCs) experiments suggested that introducing MECM components helped cell adhesion and proliferation and maintained promising ability to induce cell migration. Moreover, KGN-incorporating PLGA microspheres, which were loaded on scaffolds, showed a prolonged release profile and improved the chondrogenic differentiation of SMSCs during the 14-day culture. Particularly, the PCL/MECM-KGN μS seeded by SMSCs showed the highest secretion of total collagen and aggrecan. More importantly, the synergistic effect of the MECM and sustained release of KGN can endow the PCL/MECM-KGN μS scaffolds with not only excellent cell affinity and cell vitality preservation but also chondrogenic activity. Thus, the PCL/MECM-KGN μS scaffolds are expected to have good application prospects in the field of MTE.
#1Yanhong Zhao (Tianjin Medical University)H-Index: 5
#2Xige Zhao (Tianjin Medical University)H-Index: 1
Last. Yanmei Zhao (TJU: Tianjin University)H-Index: 1
view all 11 authors...
Repair of articular cartilage defects is a challenging aspect of clinical treatment. Kartogenin (KGN), a small molecular compound, can induce the differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) into chondrocytes. Here, we constructed a scaffold based on chondrocyte extracellular matrix (CECM) and poly(lactic-co-glycolic acid) (PLGA) microspheres (MP), which can slowly release KGN, thus enhancing its efficiency. Cell adhesion, live/dead staining, and CCK-8 results indicated ...
1 CitationsSource
#1Hao Li (NKU: Nankai University)H-Index: 1
#2Zhen Yang (NKU: Nankai University)H-Index: 3
Last. Quanyi Guo (NKU: Nankai University)H-Index: 27
view all 10 authors...
The meniscus plays a critical role in maintaining knee joint homeostasis. Injuries to the meniscus, especially considering the limited self-healing capacity of the avascular region, continue to be a challenge and are often treated by (partial) meniscectomy, which has been identified to cause osteoarthritis. Currently, meniscus tissue engineering focuses on providing extracellular matrix (ECM)-mimicking scaffolds to direct the inherent meniscal regeneration process, and it has been found that var...
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#1Yangyang Li (PKU: Peking University)H-Index: 9
#2Mingxue Chen (Beijing Jishuitan Hospital)H-Index: 12
Last. Quanyi Guo (Chinese PLA General Hospital)H-Index: 27
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Abstract Considering the intrinsic poor self-healing capacity of meniscus, tissue engineering has become a new direction for the treatment of meniscus lesions. However, disturbed by mechanical stability and biocompatibility, most meniscus implants fail to relieve symptoms and prevent the development of osteoarthritis. The goal of this study was to develop a potential meniscal substitute for clinical application. Here, silk fibroin with good mechanical performance and biocompatibility, and stront...
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#1Negin Asgari (TMU: Tarbiat Modares University)H-Index: 1
#2Fatemeh Bagheri (TMU: Tarbiat Modares University)H-Index: 11
Last. Amir Mohammad Ghafari (Åbo Akademi University)H-Index: 2
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BACKGROUND Regeneration of articular cartilage poses a tremendous challenge due to its limited self-repair capability and inflammation at the damaged site. To generate the desired structures that mimic the structure of native tissue, microtissues with repeated functional units such as cell aggregates have been developed. Multicellular aggregates of mesenchymal stem cells (MSCs) can be used as microscale building blocks of cartilage due to their potential for cell-cell contact, cell proliferation...
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#1Ling Zhu (JNU: Jinan University)H-Index: 4
#2Shitian Chen (JNU: Jinan University)H-Index: 4
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Abstract We present here a porous poly (L-lactide)/chitosan (PLLA/CS) composite scaffold with micro/nano-fiber hierarchical structure that was innovatively fabricated by combining 3D printing and thermally induced phase separation technology. Moreover, bioactive quercetin (Qu) was chosen to further functionalize the PLLA/CS scaffold with polydopamine (PDA) layer. The final results showed that the hydrophilicity and mechanical properties of the resulting PLLA/CS-D/Qu scaffold were obviously super...
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#1Cristian De Gregorio (Universidad del Desarrollo)H-Index: 2
#2David Contador (Universidad del Desarrollo)H-Index: 8
Last. Fernando Ezquer (Universidad del Desarrollo)H-Index: 19
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BACKGROUND: Diabetic polyneuropathy (DPN) is the most common and early developing complication of diabetes mellitus, and the key contributor for foot ulcers development, with no specific therapies available. Different studies have shown that mesenchymal stem cell (MSC) administration is able to ameliorate DPN; however, limited cell survival and safety reasons hinder its transfer from bench to bedside. MSCs secrete a broad range of antioxidant, neuroprotective, angiogenic, and immunomodulatory fa...
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#1Zong Li (PKU: Peking University)H-Index: 5
#2Nier Wu (PKU: Peking University)H-Index: 3
Last. Yingfang Ao (PKU: Peking University)H-Index: 30
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Meniscus deficiency, the most common and refractory disease in human knee joints, often progresses to osteoarthritis (OA) due to abnormal biomechanical distribution and articular cartilage abrasion. However, due to its anisotropic spatial architecture, complex biomechanical microenvironment, and limited vascularity, meniscus repair remains a challenge for clinicians and researchers worldwide. In this study, we developed a 3D printing-based biomimetic and composite tissue-engineered meniscus scaf...
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#1Shuo Zhang (HUST: Huazhong University of Science and Technology)H-Index: 3
#2Binwu Hu (HUST: Huazhong University of Science and Technology)H-Index: 10
Last. Zengwu Shao (HUST: Huazhong University of Science and Technology)H-Index: 26
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Abstract Background Trauma- or osteoarthritis-related cartilage damage resulted in functional decline of joints and heavy burden of public health. Recently, the reparative role of mesenchymal stem/progenitor cells (MSCs) in articular cartilage (AC) reconstruction is drawing more and more attention. Objective To provide a review on (1) the locations and categories of joint-resident MSCs, (2) the regulation of chondrogenic capacities of MSCs, (3) the migratory approaches of MSCs to diseased AC and...
13 CitationsSource
#1Mingxue Chen (Chinese PLA General Hospital)H-Index: 12
#2Zhaoxuan Feng (USTB: University of Science and Technology Beijing)H-Index: 1
Last. Quanyi Guo (Chinese PLA General Hospital)H-Index: 27
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Regeneration of an injured meniscus continues to be a scientific challenge, due to its poor self-healing potential. Tissue engineering provides an avenue for regenerating a severely damaged meniscus. In this study, we first investigated the superiority of five concentrations (0%, 0.5%, 1%, 2% and 4%) of meniscus extracellular matrix (MECM)-based hydrogel in promoting cell proliferation and the matrix-forming phenotype of meniscal fibrochondrocytes (MFCs). We found that the 2% group strongly enha...
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#1Wei Yang (JNU: Jinan University)H-Index: 6
#2Ping Zhu (Cardiovascular Institute of the South)H-Index: 2
Last. Rui Guo (JNU: Jinan University)H-Index: 19
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Here, kartogenin (KGN), an emerging stable nonprotein compound with the ability to promote differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) into chondrocytes, was grafted onto the surface of modified ultrasmall superparamagnetic iron-oxide (USPIO) and then integrated into cellulose nanocrystal/dextran hydrogels. The hydrogels served as a carrier for the USPIO-KGN and a matrix for cartilage repair. We carried out in vitro and in vivo studies, the results of which demonstrated...
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