The immune microenvironment in cartilage injury and repair

Acta Biomaterialia, Год журнала: 2021, Номер 140, С. 23 - 42

Опубликована: Дек. 10, 2021

The ability of articular cartilage to repair itself is limited because it lacks blood vessels, nerves, and lymph tissue. Once damaged, can lead joint swelling pain, accelerating the progression osteoarthritis. To date, complete regeneration hyaline exhibiting mechanical properties remains an elusive goal, despite many available technologies. inflammatory milieu created by damage critical for chondrocyte death hypertrophy, extracellular matrix breakdown, ectopic bone formation, injury In microenvironment, mesenchymal stem cells (MSCs) undergo aberrant differentiation, chondrocytes begin convert or dedifferentiate into with a fibroblast phenotype, thereby resulting in fibrocartilage poor qualities. All these factors suggest that problems may be major stumbling block repair. produce conducive repair, multi-dimensional management microenvironment place time required. Therefore, this calls elucidation immune after injury. This review provides brief overview of: (1) pathogenesis injury; (2) repair; (3) effects cytokines on (4) clinical strategies treating defects; (5) targeted immunoregulation Immune response increasingly considered key factor affecting It has both negative positive regulatory process Proinflammatory are secreted large numbers, necrotic removed. During period, secrete anti-inflammatory chondrogenic cytokines, which inhibit inflammation promote However, persist, accelerate degradation matrix. Furthermore, MSCs abnormal transform fibroblast-like cells, forming properties. Consequently, requires regulation space make regeneration.

Язык: Английский

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Hydrogel composite scaffolds achieve recruitment and chondrogenesis in cartilage tissue engineering applications

Journal of Nanobiotechnology, Год журнала: 2022, Номер 20(1)

Опубликована: Янв. 6, 2022

The regeneration and repair of articular cartilage remains a major challenge for clinicians scientists due to the poor intrinsic healing this tissue. Since injuries are often clinically irregular, tissue-engineered scaffolds that can be easily molded fill defects any shape fit tightly into host needed.In study, bone marrow mesenchymal stem cell (BMSC) affinity peptide sequence PFSSTKT (PFS)-modified chondrocyte extracellular matrix (ECM) particles combined with GelMA hydrogel were constructed.In vitro experiments showed pore size porosity solid-supported composite appropriate provided three-dimensional microenvironment supporting adhesion, proliferation chondrogenic differentiation. In also GelMA/ECM-PFS could regulate migration rabbit BMSCs. Two weeks after implantation in vivo, functional scaffold system promoted recruitment endogenous cells from defect site. achieved successful hyaline rabbits while control treatment mostly resulted fibrous tissue repair.This combination chondrogenesis is an ideal strategy repairing irregular defects.

Язык: Английский

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Living and Injectable Porous Hydrogel Microsphere with Paracrine Activity for Cartilage Regeneration

Small, Год журнала: 2023, Номер 19(17)

Опубликована: Янв. 18, 2023

Abstract Paracrine is an important mechanism in mesenchymal stem cells (MSCs) that promotes tissue regeneration. However, anoikis attributed to unsuitable adhesion microenvironment hindered this paracrine effect. In study, a living and injectable porous hydrogel microsphere with long‐term activity constructed via the freeze‐drying microfluidic technology incorporation of platelet‐derived growth factor‐BB (PDGF‐BB) exogenous MSCs. Benefiting from structure superior mechanical property methacrylate gelatin (GelMA) microspheres (GMs), are able adhere proliferate on GMs, thereby facilitating cell‐to‐extracellular matrix (ECM) cell‐to‐cell interactions enhancing Furthermore, sustained release PDGF‐BB can recruit endogenous MSCs prolong GMs. vitro vivo experiments validated GMs exhibit secretion properties anti‐inflammatory efficacy attenuate osteoarthritis (OA) progression by favoring adherent utilizing synergistic effect Overall, enhance fabricated anticipated hold potential future clinical translation OA other diseases.

Язык: Английский

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Stem Cell‐Recruiting Injectable Microgels for Repairing Osteoarthritis

Advanced Functional Materials, Год журнала: 2021, Номер 31(48)

Опубликована: Июль 17, 2021

Abstract The differentiation potentials and viability of stem cells are often impaired during cell isolation delivery. Inspired by the phenomenon where islands can recruit seabirds for nesting, “cell island” microgels (MGs), that is, growth factor‐loaded methacrylated hyaluronic acid heparin blend MGs, which endogenous promote chondrogenic differentiation, constructed using microfluidic technology photopolymerization processes, followed non‐covalently binding platelet‐derived factor‐BB (PDGF‐BB) transforming factor‐beta3 (TGF‐β3). loading efficiency PDGF‐BB TGF‐β3 96% 91%, respectively. In vitro in vivo experiments find MGs enhance migratory capacity them from their niche via releasing PDGF‐BB. Meanwhile, acid, provide a suitable microenvironment attachment spreading. Furthermore, induce recruited present promising therapeutic effect osteoarthritis. sum, this developed MG might serve as temporary “nest site” to allow migration, adhesion, cells, be candidate rather than conventional cell‐seeded scaffolds promoting tissue regeneration.

Язык: Английский

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Cell-free decellularized cartilage extracellular matrix scaffolds combined with interleukin 4 promote osteochondral repair through immunomodulatory macrophages: In vitro and in vivo preclinical study

Acta Biomaterialia, Год журнала: 2021, Номер 127, С. 131 - 145

Опубликована: Апрель 1, 2021

Cartilage regeneration is a complex physiological process. Synovial macrophages play critical immunomodulatory role in the acute inflammatory response surrounding joint injury. Due to contrasting differences and heterogeneity of macrophage, phenotype are key determinants healing after cartilage Biomaterials derived from extracellular matrix have been used for repair reconstruction variety tissues by modulating host macrophage response. However, effect decellularized (ECM) on has not elucidated. It necessary clarify properties (DCM) guide design materials. Here, we prepared porcine articular DCM determined mouse bone marrow-derived (BMDMs) pepsin-solubilized (PDCM) vitro. Macrophages activated PDCM could promote mesenchymal stem cells (BMSCs) invasion, migration, proliferation, chondrogenic differentiation. Then, verified that early optimization effects cell-free scaffold using IL-4 vivo achieve good rat knee osteochondral defect model. Therefore, this ECM combined with accurate active strategies provides new approach development This work reports an strategy improve regeneration. Our findings demonstrated polarize constructive phenotype. These polarized promoted cell scaffolds early-stage intra-articular injection created wound-healing microenvironment improved

Язык: Английский

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3D-Bioprinted Difunctional Scaffold for In Situ Cartilage Regeneration Based on Aptamer-Directed Cell Recruitment and Growth Factor-Enhanced Cell Chondrogenesis

ACS Applied Materials & Interfaces, Год журнала: 2021, Номер 13(20), С. 23369 - 23383

Опубликована: Май 12, 2021

Articular cartilage (AC) lesions are fairly common but remain an obstacle for clinicians and researchers due to their poor self-healing capacity. Recently, a promising therapy based on the recruitment of autologous mesenchymal stem cells (MSCs) has been developed regeneration full-thickness defects in knee joint. In this study, 3D-bioprinted difunctional scaffold was aptamer HM69-mediated MSC-specific growth factor-enhanced cell chondrogenesis. The aptamer, which can specifically recognize recruit MSCs, first chemically conjugated decellularized extracellular matrix then mixed with gelatin methacrylate form photocrosslinkable bioink ready 3D bioprinting. Together factor that promoted chondrogenic differentiation, biodegradable polymer poly(ε-caprolactone) further chosen impart mechanical strength bioprinted constructs. recruited provided favorable microenvironment adhesion proliferation, chondrogenesis, thus greatly improved repair rabbit defects. conclusion, study demonstrated bioprinting scaffolds could be strategy situ AC aptamer-directed growth-factor-enhanced

Язык: Английский

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Advanced applications of cellulose-based composites in fighting bone diseases

Composites Part B Engineering, Год журнала: 2022, Номер 245, С. 110221 - 110221

Опубликована: Авг. 16, 2022

Язык: Английский

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Nanosilicate‐Reinforced Silk Fibroin Hydrogel for Endogenous Regeneration of Both Cartilage and Subchondral Bone

Advanced Healthcare Materials, Год журнала: 2022, Номер 11(17)

Опубликована: Июнь 24, 2022

Abstract Osteochondral defects are characterized by injuries to both cartilage and subchondral bone, which is a result of trauma, inflammation, or inappropriate loading. Due the unique biological properties bone cartilage, developing tissue engineering scaffold that can promote dual‐lineage regeneration simultaneously remains great challenge. In this study, microporous nanosilicate‐reinforced enzymatically crosslinked silk fibroin (SF) hydrogel fabricated introducing montmorillonite (MMT) nanoparticles via intercalation chemistry. vitro studies show SF‐MMT nanocomposite has improved mechanical hydrophilicity, as well bioactivities osteogenic differentiation marrow mesenchymal stem cells maintain chondrocyte phenotype compared with SF hydrogel. Global proteomic analysis verifies hydrogel, probably regulated multiple signaling pathways. Furthermore, it observed biophysical interaction partially mediated clathrin‐mediated endocytosis its downstream processes. vivo, effectively promotes osteochondral evidenced macroscopic, micro‐CT, histological evaluation. conclusion, functionalized developed bioactivity for regeneration, indicating potential in engineering.

Язык: Английский

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In situ self-assembled organoid for osteochondral tissue regeneration with dual functional units

Bioactive Materials, Год журнала: 2023, Номер 27, С. 200 - 215

Опубликована: Апрель 10, 2023

The regeneration of hierarchical osteochondral units is challenging due to difficulties in inducing spatial, directional and controllable differentiation mesenchymal stem cells (MSCs) into cartilage bone compartments. Emerging organoid technology offers new opportunities for regeneration. In this study, we developed gelatin-based microcryogels customized using hyaluronic acid (HA) hydroxyapatite (HYP), respectively (denoted as CH-Microcryogels OS-Microcryogels) through vivo self-assembly organoids. showed good cytocompatibility induced chondrogenic osteogenic MSCs, while also demonstrating the ability self-assemble organoids with no delamination biphasic cartilage-bone structure. Analysis by mRNA-seq that promoted inhibited inflammation, OS-Microcryogels facilitated suppressed immune response, regulating specific signaling pathways. Finally, engraftment pre-differentiated canine defects resulted spontaneous assembly an unit, simultaneous both articular subchondral bone. conclusion, novel approach generating self-assembling utilizing tailor-made presents a highly promising avenue advancing field tissue engineering.

Язык: Английский

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Engineered biochemical cues of regenerative biomaterials to enhance endogenous stem/progenitor cells (ESPCs)-mediated articular cartilage repair

Bioactive Materials, Год журнала: 2023, Номер 26, С. 490 - 512

Опубликована: Май 2, 2023

As a highly specialized shock-absorbing connective tissue, articular cartilage (AC) has very limited self-repair capacity after traumatic injuries, posing heavy socioeconomic burden. Common clinical therapies for small- to medium-size focal AC defects are well-developed endogenous repair and cell-based strategies, including microfracture, mosaicplasty, autologous chondrocyte implantation (ACI), matrix-induced ACI (MACI). However, these treatments frequently result in mechanically inferior fibrocartilage, low cost-effectiveness, donor site morbidity, short-term durability. It prompts an urgent need innovative approaches pattern pro-regenerative microenvironment yield hyaline-like with similar biomechanical biochemical properties as healthy native AC. Acellular regenerative biomaterials can create favorable local environment without causing relevant regulatory scientific concerns from treatments. A deeper understanding of the mechanism healing is furthering (bio)design application scaffolds. Currently, utilization magnify repairing effect joint-resident stem/progenitor cells (ESPCs) presents evolving improvement repair. This review starts by briefly summarizing current vital roles ESPCs chemoattractants regeneration. Then several intrinsic hurdles biomaterials-based discussed. The recent advances novel regarding cues provide instructive extracellular guide (e.g. adhesion, migration, proliferation, differentiation, matrix production, remodeling) summarized. Finally, this outlines future directions engineering next-generation toward ultimate translation.

Язык: Английский

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