Injectable hypoxia-preconditioned cartilage progenitor cells-laden GelMA microspheres system for enhanced osteoarthritis treatment

Feng, Kai; Yu, Yifan; Chen, Zhengsheng; Wang, Rui; Zhang, Kunqi; Chen, Hongfang; Xu, Jia; Kang, Qinglin

doi:10.1016/j.mtbio.2023.100637

Cited by 4 publications

(7 citation statements)

References 59 publications

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“…Methacrylic acid modified gelatin (GelMA) has good biological properties and adjustable physical properties, and is widely used in tissue engineering in bone, cartilage, heart and other fields. GelMA is a highly attractive hydrogel with photocrosslinking properties, making it successful in maintaining suitable biological properties, tunable physical characteristics, and pleiotropic collaboration functions with other delivery systems [ 61 , 62 ]. GelMA coating is a critical technical improvement of exosome-based drug delivery in this study.…”

Section: Discussionmentioning

confidence: 99%

Injectable photocrosslinking spherical hydrogel-encapsulated targeting peptide-modified engineered exosomes for osteoarthritis therapy

Wan,

He,

Peng

et al. 2023

J Nanobiotechnol

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Osteoarthritis (OA) is a common degenerative joint disease urgently needing effective treatments. Bone marrow mesenchymal stromal cell-derived exosomes (Exo) are considered good drug carriers whereas they have limitations such as fast clearance and low retention. This study aimed to overcome the limitations of Exo in drug delivery using multiple strategies. Novel photocrosslinking spherical gelatin methacryloyl hydrogel (GelMA)-encapsulated cartilage affinity WYRGRL (W) peptide-modified engineered Exo were developed for OA treatment and the performance of the engineered Exo (W-Exo@GelMA) loaded with a small inhibitor LRRK2-IN-1 (W-Exo-L@GelMA) was investigated in vitro and in vivo. The W-Exo-L@GelMA showed an effective targeting effect on chondrocytes and a pronounced action on suppressing catabolism and promoting anabolism in vitro. Moreover, W-Exo-L@GelMA remarkably inhibited OA-related inflammation and immune gene expression, rescuing the IL-1β-induced transcriptomic responses. With enhanced retention in the joint, W-Exo-L@GelMA demonstrated superior anti-OA activity and cartilage repair ability in the OA murine model. The therapeutic effect was validated in the cultured human OA cartilage. In conclusion, photocrosslinking spherical hydrogel-encapsulated targeting peptide-modified engineered Exo exhibit notable potential in OA therapy. Engineering Exo by a series of strategies enhanced the targeting ability and retention and cartilage-targeting and Exo-mediated drug delivery may offer a novel strategy for OA treatment.Clinical trial registration: Not applciable. Graphical Abstract

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Section: Discussionmentioning

confidence: 99%

Injectable photocrosslinking spherical hydrogel-encapsulated targeting peptide-modified engineered exosomes for osteoarthritis therapy

Wan,

He,

Peng

et al. 2023

J Nanobiotechnol

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“…[ 179 ] Many cartilage repair materials are adept at creating an optimal extracellular environment that encourages the adhesion, proliferation, and differentiation of chondrocytes, leading to the rejuvenation of cartilage tissue. [ 180,181 ]…”

Section: Multifunctional Nanomaterials For Oa Therapymentioning

confidence: 99%

Intra‐Articular Injection of Nanomaterials for the Treatment of Osteoarthritis: From Lubrication Function Restoration to Cell and Gene Therapy

Yang,

Zhang

2024

Adv Funct Materials

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Osteoarthritis (OA), a prevalent joint disease affecting many people globally, presents significant challenge in current treatments, which often only manage symptoms without halting disease progression. This review illuminates novel approaches in OA therapy, focusing mainly on intra‐articular injection of nanomaterials. The innovative materials, designed to either mimic or augment natural joint lubrication, show promise in restoring joint biomechanics and alleviating pain. The review delves into an array of biomimetic lubricants, including polymer brush, nanocomposite hydrogel, and nanoparticles, underscoring their roles in anti‐inflammation, targeting, cartilage repair, and drug delivery. Furthermore, the potential of mesenchymal stem cells to differentiate into chondrocytes, coupled with the delivery of these cells and their exosomes via nanomaterials, has promoted cell therapy avenues for OA. The review also highlights the function of non‐coding RNAs such as miRNA, siRNA, circRNA, lncRNA, and antisense oligonucleotides in impeding OA progression, with nanomaterials facilitating their delivery, thus facilitating advanced therapeutic possibilities including immune evasion and bone cell proliferation. Overall, this review encapsulates the evolution of nanomaterials in OA treatment from material to cell, and ultimately to gene therapy, forecasting a future where nanomaterials evolve toward integrated, personalized diagnostics and therapeutics for OA.

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“…217 Feng et al discovered that when hypoxic preconditioned CPCs were cultured in a three-dimensional manner on GelMA microspheres instead of using the traditional two-dimensional method, there was better maintenance of matrix metabolic balance and alleviation of articular cartilage degeneration. 120 The differentiation of CPCs primarily favors chondrocytes, rendering them an optimal alternative to MSCs. However, the acquisition of CPCs may pose greater challenges compared to MSCs due to their requirement for isolation from specific tissues, which is arduous and carries a heightened surgical risk.…”

Section: The Delivery Of Cellsmentioning

confidence: 99%

“…Gelatin methacryloyl (GelMA) microsphere, derived from gelatin through the introduction of a polymerizable methacryloyl group, offers enhanced mechanical strength and stability via a photoinitiator and ultraviolet light by controlling substitution degree, polymer concentration, initiator concentration, and UV irradiation conditions. , Chen et al have successfully developed fibronectin-modified methylated gelatin (GelMA) microspheres with independently adjustable elastic modulus and ligand density, enabling broad modulation of cytoskeletal dynamics and subsequent mechanobiological signaling . Due to its ability to form a robust cross-net-like structure within the 3D network, GelMA microspheres have been widely used in the delivery of bioactive factors and cells . Hyaluronic acid (HA) is a widely utilized microsphere material for OA due to its exceptional properties.…”

Section: Characteristics Of Hydrogel Microspheresmentioning

confidence: 99%

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Transforming Osteoarthritis Treatment: Embracing Hydrogel Microspheres

Chen,

Zhou,

et al. 2024

ACS Materials Lett.

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Osteoarthritis (OA) is a chronic condition characterized by degeneration of the articular cartilage and subsequent bone hyperplasia. With the increasing prevalence driven by factors such as aging and obesity, OA poses a growing health and economic burden. Current treatments, including NSAIDs and corticosteroid injections, offer limited efficacy and often result in adverse effects, highlighting the urgent need for novel therapeutic approaches. Emerging research has identified hydrogel microspheres as a promising solution for OA management. These microspheres, with their tunable physicochemical properties and biocompatibility, provide a conducive environment for cartilage regeneration and sustained drug delivery. Unlike bulk hydrogels, microspheres offer enhanced injectability, uniform distribution, and reduced tissue damage. This review discusses the recent advancements in hydrogel microsphere technology, focusing on their fabrication, unique mechanisms, and therapeutic applications in OA. Additionally, we address the challenges and future directions for clinical translation, with the aim to optimize the efficacy of hydrogel microspheres in OA treatment.

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Injectable hypoxia-preconditioned cartilage progenitor cells-laden GelMA microspheres system for enhanced osteoarthritis treatment

Cited by 4 publications

References 59 publications

Injectable photocrosslinking spherical hydrogel-encapsulated targeting peptide-modified engineered exosomes for osteoarthritis therapy

Injectable photocrosslinking spherical hydrogel-encapsulated targeting peptide-modified engineered exosomes for osteoarthritis therapy

Intra‐Articular Injection of Nanomaterials for the Treatment of Osteoarthritis: From Lubrication Function Restoration to Cell and Gene Therapy

Transforming Osteoarthritis Treatment: Embracing Hydrogel Microspheres

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