Integrated gradient tissue-engineered osteochondral scaffolds: Challenges, current efforts and future perspectives

Bioactive Materials, Год журнала: 2022, Номер 20, С. 574 - 597

Опубликована: Июль 1, 2022

The osteochondral defect repair has been most extensively studied due to the rising demand for new therapies diseases such as osteoarthritis. Tissue engineering proposed a promising strategy meet of simultaneous regeneration both cartilage and subchondral bone by constructing integrated gradient tissue-engineered scaffold (IGTEOS). This review brought forward main challenges establishing satisfactory IGTEOS from perspectives complexity physiology microenvironment tissue, limitations obtaining desired required scaffold. Then, we comprehensively discussed summarized current efforts resolve above challenges, including architecture strategies, fabrication techniques

Язык: Английский

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Three‐dimensional bioprinting biphasic multicellular living scaffold facilitates osteochondral defect regeneration

Interdisciplinary materials, Год журнала: 2024, Номер 3(5), С. 738 - 756

Опубликована: Июнь 2, 2024

Abstract Due to tissue lineage variances and the anisotropic physiological characteristics, regenerating complex osteochondral tissues (cartilage subchondral bone) remains a great challenge, which is primarily due distinct requirements for cartilage bone regeneration. For regeneration, significant amount of newly generated chondrocytes required while maintaining their phenotype. Conversely, regeneration necessitates inducing stem cells differentiate into osteoblasts. Additionally, construction interface crucial. In this study, we fabricated biphasic multicellular bioprinted scaffold mimicking natural employing three‐dimensional (3D) bioprinting technology. Briefly, gelatin‐methacryloyl (GelMA) loaded with articular marrow mesenchymal (ACs/BMSCs), serving as layer, preserved phenotype ACs promoted differentiation BMSCs through interaction between BMSCs, thereby facilitating GelMA/strontium‐substituted xonotlite (Sr‐CSH) regulated osteoblasts enhanced secretion matrix by in layer slow release bioactive ions from Sr‐CSH. GelMA, material, contributed reconstruction interface. Ultimately, demonstrated satisfactory simultaneous defects. promising strategy application 3D technology was proposed.

Язык: Английский

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Neurovascularization inhibiting dual responsive hydrogel for alleviating the progression of osteoarthritis

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Фев. 6, 2025

Abstract Treating osteoarthritis (OA) associated pain is a challenge with the potential to significantly improve patients lives. Here, we report on hydrogel for extracellular RNA scavenging and releasing bevacizumab block neurovascularization at osteochondral interface, thereby mitigating OA disease progression. The formed by cross-linking aldehyde-phenylboronic acid-modified sodium alginate/polyethyleneimine-grafted protocatechuic acid (OSAP/PPCA) sustained-release nanoparticles (BGN@Be), termed OSPPB. dynamic Schiff base bonds boronic ester allow injectability, self-healing, pH/reactive oxygen species dual responsiveness. OSPPB can inhibit angiogenesis neurogenesis in vitro. In an vivo model, intraarticular injection of accelerates healing process condyles alleviates chronic inhibiting interface. injectable represents promising technique treat pain.

Язык: Английский

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3D-bioprinted anisotropic bicellular living hydrogels boost osteochondral regeneration via reconstruction of cartilage–bone interface

The Innovation, Год журнала: 2023, Номер 5(1), С. 100542 - 100542

Опубликована: Ноя. 20, 2023

Reconstruction of osteochondral (OC) defects represents an immense challenge due to the need for synchronous regeneration special stratified tissues. The revolutionary innovation bioprinting provides a robust method precise fabrication tissue-engineered OCs with hierarchical structure; however, their spatial living cues simultaneous fulfilment osteogenesis and chondrogenesis reconstruct cartilage-bone interface OC are underappreciated. Here, inspired by natural bilayer features, anisotropic bicellular hydrogels (ABLHs) simultaneously embedding articular cartilage progenitor cells (ACPCs) bone mesenchymal stem (BMSCs) in layers were precisely fabricated via two-channel extrusion bioprinting. optimum formulation 7% GelMA/3% AlgMA hydrogel bioink was demonstrated, excellent printability at room temperature maintained high cell viability. Moreover, chondrogenic ability ACPCs osteogenic BMSCs demonstrated vitro, confirming inherent differential regulation ABLHs. In addition, ABLHs exhibited satisfactory subchondral vivo. Compared homogeneous hydrogels, neo-cartilage neo-bone augmented 23.5% 20.8%, respectively, more important, harmonious achieved well-tuned cartilage-bone-vessel crosstalk. We anticipate that such strategy tissue-mimetic ABLH means is capable spatiotemporal cell-driven regeneration, offering insights into materials reconstruction complex organ defects.

Язык: Английский

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Hydrogel Drug Delivery Systems for Bone Regeneration

Pharmaceutics, Год журнала: 2023, Номер 15(5), С. 1334 - 1334

Опубликована: Апрель 25, 2023

With the in-depth understanding of bone regeneration mechanisms and development tissue engineering, a variety scaffold carrier materials with desirable physicochemical properties biological functions have recently emerged in field regeneration. Hydrogels are being increasingly used engineering because their biocompatibility, unique swelling properties, relative ease fabrication. Hydrogel drug delivery systems comprise cells, cytokines, an extracellular matrix, small molecule nucleotides, which different depending on chemical or physical cross-linking. Additionally, hydrogels can be designed for types specific applications. In this paper, we summarize recent research using as carriers, detail application defect diseases mechanisms, discuss future directions hydrogel engineering.

Язык: Английский

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A One‐Stone‐Two‐Birds Strategy for Osteochondral Regeneration Based on a 3D Printable Biomimetic Scaffold with Kartogenin Biochemical Stimuli Gradient

Advanced Healthcare Materials, Год журнала: 2023, Номер 12(15)

Опубликована: Фев. 10, 2023

Abstract Osteochondral defect (OCD) regeneration remains challenging because of the hierarchy native tissue including both articular cartilage and subchondral bone. Constructing an osteochondral scaffold with biomimetic composition, structure, biological functionality is key to achieve its high‐quality repair. In present study, injectable 3D printable bilayered hydrogel based on compositional gradient methacrylated sodium alginate, gelatin methacryloyl, β ‐tricalcium phosphate ( ‐TCP), as well biochemical kartogenin (KGN) in two well‐integrated zones chondral layer (CLH) osseous (OLH) developed. vitro subcutaneous vivo evaluations reveal that apart from chondrogenesis embedded bone mesenchymal stem cells induced by CLH a high concentration KGN, low KGN ‐TCP OLH synergistically achieves superior osteogenic differentiation endochondral ossification, instead intramembranous ossification using only ‐TCP. The construct leveraging inducer can facilitate restoration defect. This one‐stone‐two‐birds strategy opens up new facile approach for OCD exploiting functions bioactive drug molecule KGN.

Язык: Английский

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Tough Polyurethane Hydrogels with a Multiple Hydrogen‐Bond Interlocked Bicontinuous Phase Structure Prepared by In Situ Water‐Induced Microphase Separation

Advanced Materials, Год журнала: 2024, Номер unknown

Опубликована: Дек. 23, 2024

Abstract Hydrogels with mechanical performances similar to load‐bearing tissues are in demand for vivo applications. In this work, inspired by the self‐assembly behavior of amphiphilic polymers, polyurethane‐based tough hydrogels a multiple hydrogen‐bond interlocked bicontinuous phase structure through situ water‐induced microphase separation strategy developed, which poly(ethylene glycol)‐based polyurethane (PEG‐PU, hydrophilic) and poly(ε‐caprolactone)‐based (PCL‐PU, hydrophobic) blended form dry films followed water swelling. A hydrogen bonding factor, imidazolidinyl urea, is introduced into synthesis two polyurethanes, formation bonds between PEG‐PU PCL‐PU can promote homogeneous construction structures hydrogel network, features break strength 12.9 MPa, fracture energy 2435 J m −2 , toughness 48.2 MJ −3 . As biomedical patch, outstanding withstand abdominal pressure prevent hernia wall defect model. Compared commercial PP mesh, tissue/organ adhesion reduce inflammatory responses angiogenesis, thereby accelerating repair defects. This work may provide useful inspiration researchers design different gel materials solvent‐induced separation.

Язык: Английский

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Enhanced osteochondral regeneration with a 3D-Printed biomimetic scaffold featuring a calcified interfacial layer

Bioactive Materials, Год журнала: 2024, Номер 36, С. 317 - 329

Опубликована: Март 8, 2024

The integrative regeneration of both articular cartilage and subchondral bone remains an unmet clinical need due to the difficulties mimicking spatial complexity in native osteochondral tissues for artificial implants. Layer-by-layer fabrication strategies, such as 3D printing, have emerged a promising technology replicating stratified zonal architecture varying microstructures mechanical properties. However, dynamic circulating physiological environments, mass transportation or cell migration, usually distort pre-confined biological properties layered implants, leading undistinguished variations subsequently inefficient regenerations. This study introduced biomimetic calcified interfacial layer into scaffold compact barrier between facilitate osteogenic–chondrogenic repair. consisting polycaprolactone (PCL), nano-hydroxyapatite, tasquinimod (TA) can physically biologically separate (TA-mixed, chondrocytes-load gelatin methacrylate) from bond (porous PCL). introduction preserved as-designed independent environment each regeneration, successfully inhibiting vascular invasion preventing hyaluronic calcification owing devascularization TA. improved was validated through gross examination, micro-computed tomography (micro-CT), histological immunohistochemical analyses based on vivo rat model. Moreover, gene protein expression studies identified key role Caveolin (CAV-1) promoting angiogenesis Wnt/β-catenin pathway indicated that TA blocked by CAV-1.

Язык: Английский

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Stage-specific and location-specific cartilage calcification in osteoarthritis development

Annals of the Rheumatic Diseases, Год журнала: 2022, Номер 82(3), С. 393 - 402

Опубликована: Окт. 19, 2022

This study investigated the stage-specific and location-specific deposition characteristics of minerals in human osteoarthritis (OA) cartilages via multiple nano-analytical technologies.Normal OA were serially sectioned for micro-CT, scanning electron microscopy with energy dispersive X-ray spectroscopy, micro-Raman focused ion beam microscopy, high-resolution loss spectrometry transmission nanoindentation atomic force to analyse structural, compositional mechanical properties cartilage progression.We found that progressed by both top-down calcification at joint surface bottom-up osteochondral interface. The process started spherical mineral particle formation during early-stage (OA-E), followed fibre densely packed material transformation deep into advanced-stage (OA-A). OA-E when an excessive layer calcified tissue formed above original cartilage, exhibiting a sandwich structure. Over time, upper layers fused, which thickened region disrupted During OA-E, was hypermineralised, containing stiffer carbonated hydroxyapatite (HAp). OA-A, it hypomineralised contained softer HAp. discrepancy may be attributed matrix vesicle nucleation carbonate cores OA-A.This work refines our current understanding mechanism underlying progression provides foothold potential therapeutic targeting strategies once features are established.

Язык: Английский

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Gradient scaffolds for osteochondral tissue engineering and regeneration

Chemical Engineering Journal, Год журнала: 2024, Номер 498, С. 154797 - 154797

Опубликована: Авг. 13, 2024

Язык: Английский

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