{"title":"Nanotechnological approaches for the targeted delivery of CRISPR-Cas systems for genomic modifications, biomolecular sensing, and precision medicine.","authors":"Mirza Muhammad Faran Ashraf Baig, Wai Tong Chien, Sek Ying Chair","doi":"10.1039/d5bm00711a","DOIUrl":"https://doi.org/10.1039/d5bm00711a","url":null,"abstract":"<p><p>The integration strategies of CRISPR-Cas gene editing systems with nanotechnological approaches have achieved synergistic effects in targeting genes; correcting genetic disorders; and treating, sensing, and diagnosing a variety of cancers and metabolic, immunological, and complex infectious diseases-all having connectivity with distinct genetic cues and mutations. Numerous recent studies have demonstrated the use of the nano-scale properties of nanomaterials to tremendously improve the genomic-editing efficiencies of CRISPR/Cas systems for achieving 50% enhanced bioavailability, improved cell targetability, and gene-level specificity while minimizing immunogenicity, compared with conventional/ordinary delivery techniques. Thus, nano-delivery methods utilizing the unique properties of nanomaterials, molecular interactions, biocompatibility, targeted cellular uptake, and nuclear delivery capability effectively overcame the challenges of inefficient biomolecular delivery, and off-target effects were effectively overcome. Nano -carriers made up of materials such as DNA lattices, lipids, dendrimers, polymers, peptides, and metals (gold, silver, <i>etc</i>.) that were explored for facilitating the precise delivery of CRISPR/Cas components, sensing biomolecules, and diagnostic purposes are discussed in this review report. The ability of DNA scaffold materials to incorporate nano-CRISPR systems, to sense biomolecules, and for targeted cellular delivery of payloads (<i>e.g.</i>, Cas9, Cas12, Cas13, and Cas14 proteins and single-guide RNAs (sgRNAs)) maximized gene targeting and improved therapeutic outcomes while achieving up to 90% efficiency compared with common/trivial delivery methods.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tao Zhang, Lifei Huang, Xiaonan Zhang, Jiali Guo, Yunming Shen, Yongxiang Luo
{"title":"3D printed bioceramic scaffolds with fully interconnected channel networks for enhanced vascularized bone regeneration.","authors":"Tao Zhang, Lifei Huang, Xiaonan Zhang, Jiali Guo, Yunming Shen, Yongxiang Luo","doi":"10.1039/d5bm00824g","DOIUrl":"https://doi.org/10.1039/d5bm00824g","url":null,"abstract":"<p><p>Bioceramics have emerged as some of the most widely utilized and promising biomaterials for bone repair. The structural morphology of bioceramic scaffolds plays a critical role in determining their overall performance. Strategic morphological design and optimization have been demonstrated to substantially augment therapeutic outcomes. Herein, in this study, we present a strategy for fabricating β-tricalcium phosphate (β-TCP) bioceramic scaffolds featuring a dual-pore architecture comprising fully interconnected hollow channel networks and open macropores, achieved through extrusion-based 3D printing coupled with surface crosslinking. The manufacturing process enables simultaneous structural optimization and bioactive ion incorporation (<i>e.g.</i>, Cu<sup>2+</sup>, Sr<sup>2+</sup>) during surface crosslinking. Comparative <i>in vitro</i> and <i>in vivo</i> evaluations revealed that the interconnected channel system significantly enhanced mass transport efficiency and cellular infiltration, leading to superior bone tissue ingrowth and vascularization compared to both non-channeled scaffolds and those with non-interconnected channels fabricated by coaxial 3D printing. This work establishes the following advances: integration of macropores with fully interconnected channel networks in bioceramic scaffolds using extrusion-based additive manufacturing, and demonstration of enhanced vascularized osteogenesis through optimized structural design. The findings provide insights into the rational design of advanced bioceramic scaffolds for functional bone regeneration.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Elvan Dogan, Ann Austin, Ayda Pourmostafa, Swaprakash Yogeshwaran, Hossein Goodarzi Hosseinabadi, Amir K Miri
{"title":"Design considerations for photoinitiator selection in cell-laden gelatin methacryloyl hydrogels.","authors":"Elvan Dogan, Ann Austin, Ayda Pourmostafa, Swaprakash Yogeshwaran, Hossein Goodarzi Hosseinabadi, Amir K Miri","doi":"10.1039/d5bm00550g","DOIUrl":"https://doi.org/10.1039/d5bm00550g","url":null,"abstract":"<p><p>Light-assisted bioprinting of protein-derived hydrogels has been widely used for tissue engineering and regenerative medicine. The practical challenges of the photoinitiators (PIs) are often overlooked in using photo-crosslinkable bioinks for <i>in situ</i> and <i>in vitro</i> applications. A higher concentration of PI is believed to increase the network density of a hydrogel thus reducing its mass transfer capacity, but PI can form reactive oxygen species (ROS) and cause unwanted side reactions around biological compartments. This study systematically investigates the role of ROS generation on mesenchymal stem cells encapsulated in gelatin-methacryloyl hydrogels when using type I PIs-<i>e.g.</i> lithium phenyl(2,4,6-trimethyl-benzoyl)phosphinate and 2-hydroxy-1-(4-hydroxyethyl-phenyl)-2-methyl-1-propanone, and type II PI-<i>e.g.</i> Eosin Y. The results reveal that higher concentrations of type I PIs provide a higher elastic modulus at the expense of enhanced ROS generation and a proportional decrease in viability. We report a novel hydrogel system with minimal PI loading where a reduction in elastic modulus is accompanied by a simultaneous decrease in pore size and ROS level leading to a significant increase in stem cell viability over one week of <i>in vitro</i> culture. In contrast, the type II PI reveals a moderate fluctuation of elastic modulus over a range of PI concentration correlated to fluctuations in ROS generation. Monitoring ROS level variations enables evaluation of each PI's impact on cell response, providing a strategy for the biofabrication of cell-laden constructs. This framework can inform the rational design of photo-crosslinkable hydrogels for light-assisted bioprinting and <i>in situ</i> crosslinking applications in regenerative medicine.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Injectable lubricant-coated hyaluronic acid-dopamine for the repair of early osteoarthritis.","authors":"Hang Yao, Chirun Wang, Qi Tao, Jian Yang, Dianwei Liu, Xianfeng Shang, Zhonglian Wu, Xu Hu, Zehao Gu, Zhilin Cheng, Jihang Dai, Dong-An Wang","doi":"10.1039/d5bm00603a","DOIUrl":"https://doi.org/10.1039/d5bm00603a","url":null,"abstract":"<p><p>Osteoarthritis (OA) is an irreversible disease of continuous degradation of cartilage, and natural joint super-lubrication is thought to provide hydrated lubrication to articular cartilage. Synovial joint fluid consists of hyaluronic acid (HA) and numerous brush-like macromolecules, exhibits a high affinity for cartilage proteins, and forms a hydrated layer on the cartilage surface. When cartilage friction increases, the surface layer of the cartilage becomes ruptured or damaged, and the cartilage hydration layer is destroyed, subsequently evolving into early OA. In this study, dopamine (DOPA) was coupled with HA to modify it by utilizing the hydrophilicity of HA and the adhesive properties of DOPA. On the one hand, it enhances cartilage lubrication by prolonging the retention time of HA in cartilage and restoring the hydrated layer on the cartilage surface by adhering to the type II collagen network. The successful synthesis of hyaluronic acid-DOPA (HAD) was confirmed by nuclear magnetic resonance (NMR) hydrogen spectroscopy, infrared spectroscopy, and ultraviolet (UV) absorption spectroscopy. The morphology and hydrophilicity of HAD were demonstrated using atomic force microscopy (AFM) and contact angle measurements. Additionally, the interaction of HAD with cartilage matrix proteins was verified through confocal microscopy imaging, while the biocompatibility and feasibility of injection of HAD were confirmed by cellular and animal experiments. On the other hand, the effect of protecting and even regenerating cartilage was achieved by remodeling the cartilage microenvironment. The cartilage protection and even regeneration ability of HAD was confirmed by injecting HAD at different times after OA modeling and characterizing the joints in sections.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Peng Chen, Shaphan Jernigan, Keren Zhao, George Varghese P J, Mitesha Saha, Charles Kim, Amirhossein Arzani, Gregory Buckner, Jingjie Hu
{"title":"Image-guided embolization using Ta@Ca-Alg microspheres with optimized mechanical performance.","authors":"Peng Chen, Shaphan Jernigan, Keren Zhao, George Varghese P J, Mitesha Saha, Charles Kim, Amirhossein Arzani, Gregory Buckner, Jingjie Hu","doi":"10.1039/d5bm00797f","DOIUrl":"https://doi.org/10.1039/d5bm00797f","url":null,"abstract":"<p><p>Transcatheter arterial embolization (TAE) is a minimally invasive technique used to treat hypervascular tumors, hemorrhage, and vascular abnormalities. Though microspheres (MSs) have achieved widespread clinical use as embolic agents, they often lack imaging opacity, optimal morphology and mechanical properties which can lead to unpredictable trajectories, non-target delivery, and suboptimal embolization. This study developed tantalum-loaded calcium alginate (Ta@Ca-Alg) MSs with intrinsic radiopacity, tunable density, and mechanical properties. Ta@Ca-Alg MSs were synthesized using a gas-shearing method and analyzed for size, morphology, swelling behavior, density, radiopacity, and optimized mechanical properties. The results demonstrated that Ta@Ca-Alg MSs maintained a narrow size distribution, with increasing Ta concentration enhancing radiopacity to levels comparable with the clinical contrast agent OMNIPAQUE 350. Density and Young's modulus corresponding to different Ta concentrations were also investigated. Phantom model testing validated effective vessel occlusion and controlled penetration. <i>In vitro</i> hemocompatibility, sterility, and cytotoxicity studies confirmed excellent biocompatibility. These findings suggest that Ta@Ca-Alg MSs are a promising radiopaque embolic agent with optimized radiopacity, density, and mechanical properties, offering excellent potential for TAE procedures.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144673393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tonghui Wang, Yuji Wang, Shiming Li, Yixuan Wang, Xinmiao Lan
{"title":"Nanomedicine in ophthalmology: conquering anatomical barriers and enhancing therapeutic efficacy.","authors":"Tonghui Wang, Yuji Wang, Shiming Li, Yixuan Wang, Xinmiao Lan","doi":"10.1039/d5bm00325c","DOIUrl":"https://doi.org/10.1039/d5bm00325c","url":null,"abstract":"<p><p>Ocular diseases pose a significant threat to vision and even lead to irreversible blindness, severely impacting patients' quality of life. Traditional ocular therapies often fall short of providing effective treatment due to the unique anatomical structure of the eye, particularly in the penetration of eye barriers. Recent advancements in nanotechnology have demonstrated significant potential for addressing these limitations. Nanocarrier-based drug delivery systems offer unique advantages such as sustained drug release, enhanced bioavailability, and specific tissue targeting, which can effectively pass through barriers and act on the lesion site. In this review, we systematically examine the common routes for nano-ocular drug administration and highlight the advantages of nanomedicines in ocular drug delivery. We provide a comprehensive analysis of various nanomaterial platforms, including nanoparticles, nanomicelles, nanosuspensions, nano/microemulsions, nanowafers, and hydrogels. While acknowledging the remarkable potential of nanodrugs in controlled release, barrier penetration, and formulation diversity, we emphasize the need for further research into long-term biocompatibility and clinical validation of novel nanotherapeutic agents.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144673396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Biomimetic vascular scaffolds <i>via</i> hybrid 3D printing-phase separation for vascularized cardiac tissue with enhanced perfusion and maturation.","authors":"Xinyao Pan, Sitian Liu, Meng Long, Ruijun Peng, Lanlan Hu, Liu Yu, Wenhua Huang","doi":"10.1039/d5bm00734h","DOIUrl":"https://doi.org/10.1039/d5bm00734h","url":null,"abstract":"<p><p>Cardiac tissue engineering (CTE) shows great potential for repairing chronic myocardial damage. However, inadequate vascularization in engineered myocardial constructs thicker than 200 μm limits nutrient perfusion and leads to core necrosis, restricting its clinical application. Here, we combine 3D printing with phase separation to fabricate biomimetic vascular scaffolds, polycaprolactone (PCL) tubes, exhibiting enhanced mechanical resilience and biocompatibility. The PCL-tube facilitates the self-assembly of human umbilical vein endothelial cells (HUVECs) into microvascular networks that recapitulate the barrier functions of native vasculature, enabling selective molecular transport while preserving structural integrity. The endothelialized PCL-tube (ECs-PCL-tube) is integrated with cardiomyocyte (CM)-loaded fibrinogen-GelMA (FG) hydrogel through modular assembly to form a multi-scale, vascularized engineered cardiac tissue. The results show that the ECs-PCL-tubes significantly improve cell viability and enhance nutrient perfusion efficiency. Furthermore, the vascularized engineered cardiac tissue exhibited superior CM sarcomere formation, gap junction expression, and contractility, promoting enhanced cell-cell communication. In summary, our study addresses the limitations of lumen collapse and nutrient diffusion in conventional hydrogel systems, offering a scalable and cost-effective solution for constructing functional, vascularized cardiac tissues. This approach holds significant potential for applications in regenerative medicine and drug screening.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144673390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jiangyue Wang, Xinrui Zheng, Xinghai Wang, Yiruo He, Xueling Xiao, Sa Cha, Wenjie Zhang, Ding Bai, Ye Tian
{"title":"Development of a gelatin methacryloyl double-layer membrane incorporated with nano-hydroxyapatite for guided bone regeneration.","authors":"Jiangyue Wang, Xinrui Zheng, Xinghai Wang, Yiruo He, Xueling Xiao, Sa Cha, Wenjie Zhang, Ding Bai, Ye Tian","doi":"10.1039/d5bm00610d","DOIUrl":"https://doi.org/10.1039/d5bm00610d","url":null,"abstract":"<p><p>Guided bone regeneration (GBR) is an effective technique for treating bone defects, with barrier membranes playing a critical role in preventing soft tissue invasion while supporting bone formation. However, conventional collagen GBR membranes have limitations, including poor mechanical strength, high swelling ratio, rapid biodegradation, and fragile structures. In this study, we developed a heterogeneous double-layer membrane with tunable physical, chemical, and biological properties, fabricated through simple photopolymerization and lyophilization of gelatin methacryloyl (GelMA) and nanohydroxyapatite (nHA). By adjusting the crosslinking time, methacrylation degree, and nHA concentration, the cryogels showed porous microstructures with different pore sizes ranging from 93 to 360 μm. Compressive mechanical testing, swelling measurements, and <i>in vitro</i>/<i>in vivo</i> biodegradation assays confirmed that the methacrylation of gelatin increased the compressive modulus to 29.02 MPa (<i>p</i> = 0.0002), reduced the swelling ratio to 714% (<i>p</i> = 0.002), and slowed the degradation rate to 41.2% after 48 hours (<i>p</i> = 0.002). Incorporating nHA further enhanced the mechanical properties and extended the degradation time. GelMA and nHA-GelMA cryogels exhibited excellent biocompatibility and promoted osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), particularly in the nHA-GelMA cryogel with large pore sizes. We selected a GelMA cryogel with the smallest pore size for optimal barrier function and an nHA-GelMA cryogel with the highest osteogenic potential to construct the double-layer GBR membrane. In a rat calvarial defect model, this novel membrane significantly enhanced bone regeneration, demonstrating markedly improved bone volume/tissue volume (BV/TV) and bone mineral density (BMD) compared to the control group (<i>p</i> = 0.0042 and <i>p</i> = 0.0088, respectively), with efficacy comparable to that of a commercial GBR membrane. These findings demonstrate the promising potential of this simple, tunable double-layer GelMA/nHA cryogel membrane as a superior alternative for GBR applications.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144673391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Justyna Swieton, Thu Thao Pham, Anna Gromotowicz-Poplawska, Krzysztof Szczubialka, Dariusz Pawlak, Andrzej Mogielnicki, Shin-Ichi Yusa, Bartlomiej Kalaska
{"title":"Evaluation of the anticoagulant activity and safety of PMPC-PSSS and PMPC-PVBTAC block copolymers.","authors":"Justyna Swieton, Thu Thao Pham, Anna Gromotowicz-Poplawska, Krzysztof Szczubialka, Dariusz Pawlak, Andrzej Mogielnicki, Shin-Ichi Yusa, Bartlomiej Kalaska","doi":"10.1039/d5bm00406c","DOIUrl":"https://doi.org/10.1039/d5bm00406c","url":null,"abstract":"<p><p>Unfractionated heparin (UFH) remains a widely used anticoagulant; however, its use is associated with several limitations, including an elevated risk of bleeding, the potential for heparin-induced thrombocytopenia, and the necessity for frequent monitoring. Alternative anticoagulants with a lower risk of adverse effects and more predictable pharmacokinetics are currently under investigation. This study evaluates the anticoagulant activity and safety of poly(2-methacryloyloxyethyl phosphorylcholine)-poly(sodium styrenesulfonate) (PMPC<sub>20</sub>-PSSS<sub><i>x</i></sub>, <i>x</i> = 83 and 198) anionic block copolymers and poly(2-methacryloyloxyethyl phosphorylcholine)-poly(vinylbenzyl trimethylammonium chloride) (PMPC<sub>20</sub>-PVBTAC<sub><i>y</i></sub>, <i>y</i> = 92 and 196) cationic block copolymers. PVBTAC-based cationic block copolymers exhibited stronger <i>in vitro</i> anticoagulant activity in whole blood than PSSS-based anionic block copolymers but caused adverse effects on blood cells. The PMPC<sub>20</sub>-PSSS<sub>83</sub> anionic block copolymer affected the <i>in vitro</i> activity of factors II, V, VIII, IX, X, and XII and exhibited potent anticoagulant effects in a rat model, without significant changes in haemolysis, platelet count, or cardiorespiratory parameters. Due to its high biocompatibility and strong anticoagulant effect, PMPC<sub>20</sub>-PSSS<sub>83</sub> is a promising candidate with notable therapeutic potential in clinical applications.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144673392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Grace Felciya Sekar Jeyakumar, Poornima Velswamy, Deebasuganya Gunasekaran, Alexandar Vincent Paulraj, Nivethitha Paneerselvam Manimegalai, Uma Tiruchirappalli Sivagnanam
{"title":"Injectable hybrid hydrogel-mediated calcium-sensing receptor (CaSR) activation for enhanced osteogenesis and bone remodeling.","authors":"Grace Felciya Sekar Jeyakumar, Poornima Velswamy, Deebasuganya Gunasekaran, Alexandar Vincent Paulraj, Nivethitha Paneerselvam Manimegalai, Uma Tiruchirappalli Sivagnanam","doi":"10.1039/d5bm00349k","DOIUrl":"https://doi.org/10.1039/d5bm00349k","url":null,"abstract":"<p><p>Injectable hydrogels have transfigured bone tissue engineering by offering minimally invasive solutions for treating irregularly shaped critical-size bone defects. Unlike traditional fixed-shaped bone grafts that require invasive surgeries and precise defect matching, injectable hydrogels adapt to defect geometries and accelerate healing. The hydrogels mimic the extracellular matrix with their porous, interconnected 3D architecture, promoting cell adhesion, proliferation, differentiation, vascularization, and nutrient flow, which are essential for effective bone regeneration and affirm the osteoconductivity. Chitosan-alginate hydrogels are particularly promising due to their mechanical stability, biodegradability, and ability to deliver bioactive compounds sustainably. To enhance its osteoinductive properties, bioinorganic ions such as strontium (Sr<sup>2+</sup>)-based hybrid nanocomposites have been explored. Strontium has garnered attention for its ability to activate the calcium-sensing receptor (CaSR)-mediated signaling pathways by regulating bone resorption and bone formation by various bone matrix proteins, thereby promoting bone homeostasis and regeneration. Strontium's ionic similarity to calcium enables it to act as a robust activator of CaSR, triggering pathways that enhance bone regeneration. Building on this, we developed an innovative hybrid material hydrogel by reinforcing the chitosan-alginate hydrogels with a Sr-Fe-TQ (strontium-iron-thymoquinone) nanocomposite. This bioengineered hydrogel system demonstrated excellent hemocompatibility (in human RBCs), cytocompatibility, biocompatibility, and enhanced efficiency <i>in vitro</i> in MG-63 osteoblast-like cells. <i>In vivo</i> studies using a rabbit critical-size defect model showed accelerated bone remodeling, achieving better defect closure and superior bone volume restoration (∼99%) compared to the controls. This study underscores the transformative potential of the Sr-Fe-TQ hydrogel as an injectable, osteoconductive, and osteoinductive scaffolds for critical-size defect repair. By combining minimally invasive delivery, sustained bioactive release, and superior regenerative outcomes, this hydrogel system addresses key challenges in bone tissue engineering, paving the way for next-generation biomaterials in regenerative medicine.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144673394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}