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![Strategies for hydrogels targeting the metaphysis. (A) The process of microfluidic GelMA-BP microspheres and the construction of GelMA-BP-Mg microspheres that capture Mg 2+ for the treatment of osteoporosis via an inspired "magnet" function. Reproduced with permission [79]. Copyright 2021, ACS Publications. (B) The manufacture of sCT-HA hydrogel particles, the sCT-HA-HPCH hydrogel and the sustained release process. Reproduced with permission [84]. Copyright 2020, RSC Publications. (C) Fabrication of sCT-OCA-HPCH hydrogel and its main functions. Reproduced with permission [85]. Copyright 2020, ASC Publications.](profile/Zhen-Geng-2/publication/365345667/figure/fig3/AS:11431281099034819@1669189368714/Strategies-for-hydrogels-targeting-the-metaphysis-A-The-process-of-microfluidic.png)
Strategies for hydrogels targeting the metaphysis. (A) The process of microfluidic GelMA-BP microspheres and the construction of GelMA-BP-Mg microspheres that capture Mg 2+ for the treatment of osteoporosis via an inspired "magnet" function. Reproduced with permission [79]. Copyright 2021, ACS Publications. (B) The manufacture of sCT-HA hydrogel particles, the sCT-HA-HPCH hydrogel and the sustained release process. Reproduced with permission [84]. Copyright 2020, RSC Publications. (C) Fabrication of sCT-OCA-HPCH hydrogel and its main functions. Reproduced with permission [85]. Copyright 2020, ASC Publications.
Source publication
The skeletal system is responsible for weight-bearing, organ protection, and movement. Bone diseases caused by trauma, infection, and aging can seriously affect a patient's quality of life. Bone targeted biomaterials are suitable for the treatment of bone diseases. Biomaterials with bone-targeted properties can improve drug utilization and reduce s...
Contexts in source publication
Context 1
... no research showed that non-hybrid hydrogels could target bone tissue. Several bone-targeting drugs, including bisphosphonates and oligopeptides, can be modified on hydrogels [77]. BP has been used to modify the branching chains of natural and synthetic hydrogels in order to achieve active targeting on osteoclasts and inhibit bone resorption [78] (Fig. 4A). Farbod developed a biocompatible gelatin nanoparticle (475 ± 66 nm) that displayed a strong affinity with mineralized surfaces by conjugating alendronic acid (ALN) [80]. Gelatin nanoparticles were prepared using a two-step desolvation method. The gelatin nanoparticles were cross-linked with glutaraldehyde (GA). Then, the residual ...
Context 2
... effects of ALN. ALN was hybridized into poly (lactide--co-glycolide) (PLGA) by solid-oil-water emulsification. To achieve long-term release, ALN-PLGA nanoparticles were encapsulated in a gellan gum hydrogel [83]. Yu manufactured a nanoparticle by combining sCT and Ha (sCT-Ha) and loading the thermo-sensitive hydrogel based on hydroxypropyl chitin (Fig. 4B) [84]. They also introduced active bone-targeted nanoparticles by combining sCT and oxidized calcium alginate (OCA) via the similar approach. An excellent effect of promoting bone regeneration was reported (Fig. 4C) ...
Context 3
... manufactured a nanoparticle by combining sCT and Ha (sCT-Ha) and loading the thermo-sensitive hydrogel based on hydroxypropyl chitin (Fig. 4B) [84]. They also introduced active bone-targeted nanoparticles by combining sCT and oxidized calcium alginate (OCA) via the similar approach. An excellent effect of promoting bone regeneration was reported (Fig. 4C) ...
Citations
... | https://mc03.manuscriptcentral.com/friction substitutes and drug carriers in the treatment of cartilage related diseases [58]. The hydrophilicity of hydrogels makes them good carriers for hydrophilic drugs. ...
The good lubrication ability of articular cartilage holds significant importance in our daily lives. Osteoarthritis (OA), the most prevalent degenerative joint disease, causes cartilage damage, increased friction, and inflammation. However, the current clinical treatments for OA exhibit some defects. Recently, the sustained drug release systems with lubricating function have attracted considerable attention for treating OA. This review introduces the lubrication mechanism of cartilage, focusing particularly on the boundary lubrication mechanism. The research progress of boundary-lubricated biomaterials with drug delivery, including microcarriers, hydrogels, and nanoparticles in the treatment of OA by improving inter-articular lubrication and relieving inflammation is discussed and summarized. The efficacy and challenges of boundary-lubricated biomaterials with drug delivery in the treatment of OA are summarized, and the prospects are also discussed.
... Bone tissue engineering is a dynamic and innovative field at the forefront of regenerative medicine, tackling the complex challenge of repairing and regenerating bone tissue damaged by trauma, disease, or congenital defects [1,2]. While traditional bone repair techniques like autografting and allografting have been the cornerstone of treatments, their limitations, including donor site morbidity, limited graft supply, and potential for immune rejection, have spurred the development of alternative approaches [3][4][5]. Three-dimensional (3D) bioprinting emerges as a revolutionary technology in this landscape, offering precise control over cell and biomaterial deposition to create constructs that faithfully replicate the complex architecture of native bone tissue [6]. This cutting-edge method transcends the constraints of traditional techniques, enabling the generation of patient-specific grafts with customised shapes and functionalities that promise better integration and reduced rejection rates [7,8]. ...
In bone tissue engineering, the search for improved repair methods is crucial, given the drawbacks of traditional strategies like donor site issues and immune rejection. Addressing these challenges, this paper introduces an innovative GelMA/Bentonite composite bioink for 3D bioprinting, designed to create scaffolds that closely emulate native bone tissue. GelMA is selected for its biocompatibility and modifiable mechanics, while Bentonite's mineral richness and ion exchange capacity are harnessed to enhance scaffold structure and promote an osteogenic microenvironment. This research marks the inaugural incorporation of Bentonite into a bioink, a significant stride forward given its established safety in pharmaceuticals and versatility across industries. This bioink formulation signifies a breakthrough in bone tissue engineering, aiming to improve the osteointegration and regeneration of bone tissue. Combining Bentonite with GelMA marks a key step in creating bioinks that enhance bone healing, potentially transforming scaffold-based bone regeneration and pioneering the use of natural nanomaterials in medicine.
... The level of m 6 A modification in the motor system (namely, the musculoskeletal system) is significantly influenced by a plethora of physical and chemical factors in local environments [144,145]. Xu et al. [144] have compiled a review to summarize the METTL3/METTL14 complex's physiological activities and associated regulation mechanisms in musculoskeletal disorders. However, although there are more than 100 kinds of disorders involving the musculoskeletal system, the investigators only selected four (osteoporosis, rheumatoid arthritis, osteoarthritis, and osteosarcoma) with disparate pathogenesis and regulatory mechanism, and the enrolled studies are mostly basic ones related to METTL3/METTL14. ...
... Based on their role as precursors to osteoblasts, BMSCs are the gold standard for MSC tissue engineering treatment [1,2]. In this section, we sought to shed further light on the expression and function of m 6 A modification in the onset of osteoporosis, osteomyelitis, bone defects, and osteoarthritis, all of which are characterized by the accelerated deterioration of bone or cartilage [144,145]. Special attention was paid to in vivo studies and the possible application of m 6 A-based therapy in BMSCs. ...
The methylation of adenosine base at the nitrogen-6 position is referred to as “N6-methyladenosine (m⁶A)” and is one of the most prevalent epigenetic modifications in eukaryotic mRNA and noncoding RNA (ncRNA). Various m⁶A complex components known as “writers,” “erasers,” and “readers” are involved in the function of m⁶A. Numerous studies have demonstrated that m⁶A plays a crucial role in facilitating communication between different cell types, hence influencing the progression of diverse physiological and pathological phenomena. In recent years, a multitude of functions and molecular pathways linked to m⁶A have been identified in the osteogenic, adipogenic, and chondrogenic differentiation of bone mesenchymal stem cells (BMSCs). Nevertheless, a comprehensive summary of these findings has yet to be provided. In this review, we primarily examined the m⁶A alteration of transcripts associated with transcription factors (TFs), as well as other crucial genes and pathways that are involved in the differentiation of BMSCs. Meanwhile, the mutual interactive network between m⁶A modification, miRNAs, and lncRNAs was intensively elucidated. In the last section, given the beneficial effect of m⁶A modification in osteogenesis and chondrogenesis of BMSCs, we expounded upon the potential utility of m⁶A-related therapeutic interventions in the identification and management of human musculoskeletal disorders manifesting bone and cartilage destruction, such as osteoporosis, osteomyelitis, osteoarthritis, and bone defect.
... Thus, high dosages are required to reach the therapeutic dose, which increases the occurrence of gastro and cardiovascular side effects, consequently restricting their use (Ghlichloo and Gerriets, 2020;Markowicz-Piasecka and Mikiciuk-Olasik, 2016). A local administration, such as intra-articular injection can prevent some of the limitations observed with current treatments and potentiate their efficacy (Li et al., 2023;Zhang et al., 2023). ...
... Additionally, as a complex mixture, the composition of Matrigel is not fully defined, affecting its application specificity and predictability. Therefore, developing a hydrogel with better controllability, customizability, and a clear composition for constructing organoids is crucial for advancing regenerative medicine and tissue engineering [23]. DNA hydrogel formed by the self-assembly of DNA strands into a 3D network [24,25]. ...
Osteoarthritis (OA), a common degenerative disease, is characterized by high disability and imposes substantial economic impacts on individuals and society. Current clinical treatments remain inadequate for effectively managing OA. Organoids, miniature 3D tissue structures from directed differentiation of stem or progenitor cells, mimic native organ structures and functions. They are useful for drug testing and serve as active grafts for organ repair. However, organoid construction requires extracellular matrix-like 3D scaffolds for cellular growth. Hydrogel microspheres, with tunable physical and chemical properties, show promise in cartilage tissue engineering by replicating the natural microenvironment. Building on prior work on SF-DNA dual-network hydrogels for cartilage regeneration, we developed a novel RGD-SF-DNA hydrogel microsphere (RSD-MS) via a microfluidic system by integrating photopolymerization with self-assembly techniques and then modified with Pep-RGDfKA. The RSD-MSs exhibited uniform size, porous surface, and optimal swelling and degradation properties. In vitro studies demonstrated that RSD-MSs enhanced bone marrow mesenchymal stem cells (BMSCs) proliferation, adhesion, and chondrogenic differentiation. Transcriptomic analysis showed RSD-MSs induced chondrogenesis mainly through integrin-mediated adhesion pathways and glycosaminoglycan biosynthesis. Moreover, in vivo studies showed that seeding BMSCs onto RSD-MSs to create cartilage organoid precursors (COPs) significantly enhanced cartilage regeneration. In conclusion, RSD-MS was an ideal candidate for the construction and long-term cultivation of cartilage organoids, offering an innovative strategy and material choice for cartilage regeneration and tissue engineering.
... Hydrogels demonstrate mechanical and dimensional reactions in response to variations in their ambient conditions, including pH, temperature, and ionic concentration [8]. These behaviors show their potential for use in artificial organ fabrication, tissue reconstruction, biomedical adhesives, sensors, drug delivery systems, bone regeneration, etc. [9][10][11][12][13][14]. ...
Objective:
The objective of this review is to present a succinct summary of the latest advancements in the utilization of hydrogels for diverse biomedical applications, with a particular focus on their revolutionary impact in augmenting the delivery of drugs, tissue engineering, along with diagnostic methodologies.
Methods:
Using a meticulous examination of current literary works, this review systematically scrutinizes the nascent patterns in applying hydrogels for biomedical progress, condensing crucial discoveries to offer a comprehensive outlook on their ever-changing importance.
Results:
The analysis presents compelling evidence regarding the growing importance of hydrogels in biomedicine. It highlights their potential to significantly enhance drug delivery accuracy, redefine tissue engineering strategies, and advance diagnostic techniques. This substantiates their position as a fundamental element in the progress of modern medicine.
Conclusion:
In summary, the constantly evolving advancement of hydrogel applications in biomedicine calls for ongoing investigation and resources, given their diverse contributions that can revolutionize therapeutic approaches and diagnostic methods, thereby paving the way for improved patient well-being.
... [1][2][3] Adopting different tissue engineering International Journal of Bioprinting strategies, incorporating stem cells, utilizing advanced engineering techniques, and creating scaffold designs are among the techniques aimed at creating biostructures that are optimally conducive to cartilage regeneration. [4][5][6] Among these approaches, three-dimensional (3D) bioprinting has emerged as a potent tool, enabling precise manipulation of the spatial arrangement of cells, 7-9 biomaterials, [10][11][12] and bioactive cues [13][14][15] within three dimensions, thus emulating the intricate structure of natural tissues. Considering the distinctive tissue architecture of articular cartilage, such as low cell density and lack of vasculature, much emphasis is being placed on the careful selection of polymeric biomaterials for cartilage tissue engineering, among which hyaluronic acid (HA)-a pivotal polysaccharide constituent of the cartilage ECM and synovial fluid-has gained prominence. [16][17][18] HA offers exceptional biocompatibility, biodegradability, and low immunogenicity, playing a crucial role in maintaining cartilage structural integrity through water retention and interactions with aggrecan and type II collagen. ...
Degenerative osteoarthritis, a common sequela of articular cartilage defect, significantly impacts the quality of life of millions of individuals worldwide. Three-dimensional (3D) bioprinting has emerged as an advanced tissue engineering strategy, offering precise spatial arrangements of cells, hydrogels, and bioactive cues. Hyaluronic acid (HA) is a crucial component of bioink designed for fabricating cartilage tissue. However, creating a bioink that closely mimics the cartilaginous extracellular matrix (ECM) still remains a challenge. HA hydrogels have limitations in recapitulating tunable mechanical properties, stimuli responsiveness, and flexibility in ligands’ adhesion akin to those of native tissues. In recent years, DNA has emerged as a smart biomaterial that endows hydrogels with tunable properties and allows for precise structural customization of the hydrogels due to its unique programmability. Integrating reversible DNA linkages, reconfigurable DNA architectures, DNA plasmid, and targeted DNA aptamers into HA hydrogels allows them to respond to the extracellular environment and express desired molecules, making them ideal artificial ECMs for 3D bioprinting of cartilage tissue. This review targets this challenge by highlighting the characteristics of DNA moieties designed as reversible crosslinkers, responsive units, and adhesion ligands to functionalize HA hydrogels. Furthermore, we offer perspectives on how DNA-functionalized HA hydrogels can be harnessed to create dynamic and biomimetic bioink capable of recapitulating the more complex functions required for cartilage tissue engineering.
... In addition to the desired physical properties, high biocompatibility is imperative for the application of biodegradable hydrogels as bone repair materials [44]. To assess the cytocompatibility of the PLGA and Mg@PEG-PLGA gels, mouse embryonic fibroblasts (MEFs) and RAW264.7 cells were cultured with different gels, and cell viability was quantitatively determined using a CCK-8 assay. ...
... As reported by other researchers and our group, PLGA/NMP hydrogels are biodegradable and biocompatible and are widely used as nano/micro materials and drug carriers [31,32]. Moreover, the clinical product Eligard has been commercialized and applied for the treatment of advanced prostate cancer 44 . Herein, the in vivo biocompatibility of 2Mg@PEG-PLGA was investigated via histological and serological analysis of treated rats. ...
... Mitochondrial content, cellular structure, and matrix remodelling rate are all drastically different between fibrocartilage and subchondral bone. These variations in stress distribution between fibrocartilage and subchondral bone serve to safeguard cartilage in its natural state [74]. ...
... Mitochondrial content, cellular structure, and matrix remodelling rate are all drastically different between fibrocartilage and subchondral bone. These variations in stress distribution between fibrocartilage and subchondral bone serve to safeguard cartilage in its natural state [74]. Multiple kinds of bone transplants are accessible for bone repair. ...
Joint damage is a major symptom of osteoarthritis, a degenerative disease that worsens over time. The purpose of this review was to assess the effectiveness and safety of nanomaterials as an alternative to the widely used methods. Due to its poor regenerative and self-healing properties, cartilage repair after lesions or debilitating disease is a major clinical issue. Here, we use the organometallic chemistry identity of chondroitin sulphate to repair cartilage lesions by creating a nano-elemental particle through electrostatic interactions. As an integral part of the extracellular matrix, chondroitin sulphate (CS) is shown to improve osteogenesis in this review. The injectability of hydrated cement products was greatly improved by the addition of CS, but there was no discernible change in their phase, morphology, apparent porosity, or compressive strength. This review article provides a thorough analysis of the results from the use of nanocomposites in orthopaedic drug delivery and bone remodelling engineering.
... While the scaffold-free approach holds theoretical benefits for mimicking natural tissue morphology, combining cartilaginous organoids with suitable biomaterials can further enhance organoid generation and improve their performance. The scaffold can take various forms, such as a classic 3D construct with interconnected pores, a Matrigel or hydrogel with embedded cells, or a combination of both [79]. Solid ECMs are commonly used to promote the 3D characteristics of organoids, providing structural support to maintain cell identity and function [80]. ...
While cartilage tissue engineering has significantly improved the speed and quality of cartilage regeneration, the underlying metabolic mechanisms are complex, making research in this area lengthy and challenging. In the past decade, organoids have evolved rapidly as valuable research tools. Methods to create these advanced human cell models range from simple tissue culture techniques to complex bioengineering approaches. Cartilaginous organoids in part mimic the microphysiology of human cartilage and fill a gap in high-fidelity cartilage disease models to a certain extent. They hold great promise to elucidate the pathogenic mechanism of a diversity of cartilage diseases and prove crucial in the development of new drugs. This review will focus on the research progress of cartilaginous organoids and propose strategies for cartilaginous organoid construction, study directions, and future perspectives.
