Acta biomaterialia最新文献

{"title":"MXene-chitosan photo-responsive conduit for wireless optogenetic stimulation to enhance neural regeneration and functional recovery after optic nerve injury.","authors":"Enoch Obeng, Zhenyuan Xie, Zhixing Li, Wenyi Zhang, Wei Wang, Yuanli Wang, Yan Zheng, Zhaorong Wang, Haojie Zhang, Lanfang Sun, Qingqing Yao, Wencan Wu","doi":"10.1016/j.actbio.2025.08.045","DOIUrl":"10.1016/j.actbio.2025.08.045","url":null,"abstract":"<p><p>Optic nerve injury triggers progressive degeneration of retinal ganglion cells (RGCs) and axonal loss, driven by inhibitory microenvironmental factors such as glial scarring, myelin debris, and growth-inhibitory signaling. Physical stimuli such as photothermal and photoelectric stimulations have gained attention, yet little is known about their potential on normal cells or the optic nerve due to setbacks from over-exposure. Photothermal stimulus presents photoelectric cues and, at the same time, energy conversion for heat generation. Herein, a bio-functional platform was designed by incorporating W_1.33C i-MXene into a chitosan solution, further crosslinked with Genipin to give a porous, interconnected, and biodegradable conduit. The photoelectric platform allowed neural differentiation of PC12 cells through a substantial effect on the Calcium (Ca²⁺) ion channel. Further, we used the optic nerve crush (ONC) model to investigate the photo-stimulation effect of the conduit after ONC. Light stimulation of the WMC conduit promoted the protection of RGC and improved the visual function by modulating neural-related proteins and the downstream signaling cascade for nerve regeneration through the l-type voltage-gated calcium channel (L-VGCC). This multifunctional platform synergistically combines MXene's photoconductivity with chitosan's biocompatibility, establishing a scalable strategy for wireless neural stimulation and tissue engineering-mediated functional recovery after central nervous system injury. STATEMENT OF SIGNIFICANCE: The objective of this study was to design and fabricate a bio-functional, porous, and biodegradable platform by incorporating MXene into chitosan. This new conduit was expected to act as a photoelectric platform, allowing neural differentiation through a substantial effect on the calcium ion channel. W_1.33C i-MXene-chitosan (WMC) was the representative platform under a photothermal stimulus characterized by photoelectric cue and energy conversion to generate heat. In a rat optic nerve crush model, the conduit induced the protection of RGC and improved visual function by modulating neural-related proteins and the downstream signaling cascade for nerve regeneration through the l-type voltage-gated calcium channel (L-VGCC). This multifunctional platform synergistically combines MXenes' photoconductivity with chitosan's biocompatibility, establishing a scalable strategy for wireless neural stimulation.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144982077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tunable photoinitiated hydrogel microspheres for quantifying cell-generated forces in complex three-dimensional environments.","authors":"Antoni Garcia-Herreros, Yi-Ting Yeh, Yunpeng Tu, Adithan Kandasamy, Juan C Del Alamo, Ernesto Criado-Hidalgo","doi":"10.1016/j.actbio.2025.08.041","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.08.041","url":null,"abstract":"<p><p>We present a high-throughput method using standard laboratory equipment and microfluidics to produce cellular force microscopy probes with controlled size and elastic modulus. Mechanical forces play crucial roles in cell biology but quantifying these forces in physiologically relevant systems remains challenging due to the complexity of the native cell environment. Polymerized hydrogel microspheres offer great promise for interrogating the mechanics of processes inaccessible to classic force microscopy methods. However, despite significant recent advances, their small size and large surface-to-volume ratio impede the high-yield production of probes with tunable, monodisperse distributions of size and mechanical properties. To overcome these limitations, we use a flow-focusing microfluidic device to generate large quantities of droplets with highly reproducible, adjustable radii. These droplets contain acrylamide gel precursor and the photoinitiator Lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP) as a source of free radicals. LAP provides fine control over microsphere polymerization due to its high molar absorptivity at UV wavelengths and moderate water solubility. The polymerized microspheres can be functionalized with different conjugated extracellular matrix proteins and embedded with fluorescent nanobeads to promote cell attachment and track microsphere deformation. As proof of concept, we measure the mechanical forces generated by a monolayer of vascular endothelial cells engulfing functionalized microspheres. Individual nanobead motions are tracked and analyzed to determine 3D traction forces via direct computation of stress from measured strain. These results reveal that the cell monolayer collectively exerts strong radial compression on the encapsulated probe, suggesting new biomechanical functions of endothelial cells that could modulate diapedesis or pathogen internalization. STATEMENT OF SIGNIFICANCE: Mechanical forces are crucial to many cell biology processes but quantifying them in complex native environments remains challenging. We address this by introducing linearly elastic probes with known mechanical properties, whose deformations can be accurately measured to infer local stresses. Specifically, we present a high-throughput method for producing polyacrylamide (PAAm) hydrogel microspheres embedded with fluorescent nanoparticles. To measure cell-generated forces in physiologically relevant systems, the probes are tracked using a 3D coherent point drift algorithm, yielding high-resolution deformation data with minimal computational cost. This method overcomes key barriers in PAAm microsphere fabrication by ensuring monodisperse size, tunable stiffness, and simple, reproducible processes suitable for most cell biology labs-making it a powerful tool for studying cellular mechanobiology.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144982148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanical and structural changes to the annulus fibrosus in response to Sub-failure cyclic loading.","authors":"Jack Seifert, Lance L Frazer, Dennis Maiman, Alok Shah, Sarah K Shaffer, Narayan Yoganandan, James B Sheehy, Timothy Bentley, Daniel P Nicolella, Brian D Stemper","doi":"10.1016/j.actbio.2025.08.047","DOIUrl":"10.1016/j.actbio.2025.08.047","url":null,"abstract":"<p><p>This study aimed to quantify how repetitive tensile loading alters the mechanical and structural properties of the annulus fibrosus (AF). Mechanical changes were evaluated through a three-step protocol involving pre-damage characterization of dynamic and viscoelastic properties, damage induction using predetermined loading cycles (n=400, 1600, 6400, 12,800) to a specified strain magnitude (11 %, 20 %, 28 %, 44 %), and post-damage characterization of the same properties. Structural changes were assessed by subjecting tissue to damage cycles and staining with hematoxylin and eosin or fluorescing collagen hybridizing peptides (F-CHP). The results showed that damage cycles induced dose-dependent changes in the elastic and viscoelastic responses of the AF, decreasing the tissue's response nearly 100 % of the pre-damage values. Quasi-static distraction to failure revealed that damage cycles influenced the transition strain magnitude, which ranged from 0.11 to 0.31, but did not alter the tissue's ultimate properties. Structural analysis demonstrated cleft formation and collagen fiber uncrimping within the matrix, correlating with the magnitude of loading. However, F-CHP staining revealed no significant differences in denatured collagen fibers between damage groups. Overall, increasing damage parameters significantly decreased the dynamic and viscoelastic properties but did not affect the ultimate properties of the AF. Structural changes indicated disruption of elastic fibers within the AF microstructure without evidence of collagen fiber fractures. These findings provide new insights into the mechanics of healthy and damaged AF tissue, offering a foundational dataset for understanding AF degeneration and injury. STATEMENT OF SIGNIFICANCE: This study investigated the dose-dependent mechanical and structural changes in the annulus fibrosus under sub-failure cyclic loading, addressing a gap in the literature regarding how such loading alters annulus fibrosus properties. By systematically varying strain magnitudes and cycle counts, the work identifies dose-dependent changes in the AF's elastic and viscoelastic behavior, along with structural alterations such as cleft formation and collagen fiber uncrimping. The integration of mechanical testing with histological analysis provides a comprehensive assessment of damage mechanisms in isolated AF tissue. These findings advance the current understanding of AF degradation and fatigue behavior, offering valuable insights for researchers studying spine biomechanics, injury prevention, and interventions aimed at mitigating spinal degeneration.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144982136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biodegradable and anti-swelling peptide-based supermolecule hydrogel for eliminating ROS and inhibiting inflammation in acute spinal cord injury repair.","authors":"Xiaolin Zhou, Yanqiu Guo, Zhan Gao, Gan Lv, Xiangyang Wang, Mengpei Zhang, Yunlong Zhou","doi":"10.1016/j.actbio.2025.08.043","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.08.043","url":null,"abstract":"<p><p>The treatment of spinal cord injury (SCI) presents a significant global medical challenge, as the difficulties associated with neuronal regeneration are compounded by elevated levels of reactive oxygen species (ROS) and an inflammatory microenvironment that ensues following SCI. Peptide-based supramolecular hydrogels exhibit robust advantages in repairing SCI due to their natural amino acid composition and biomimetic extracellular matrix characteristics following self-assembly. However, the potential for sequence designability remains underexplored, presenting an opportunity to develop highly bioactive peptide-based biomaterials. In this study, the tripeptide GHK, which is naturally present in human plasma, was incorporated into the peptide sequence (FFFGHK) to self-assembled to injectable, biodegradable and anti-swelling supramolecular hydrogel, and concurrently, endowed the supramolecular hydrogel with powerful antioxidant and anti-inflammatory functions. In vitro experiments demonstrated that FFFGHK supramolecular hydrogel was capable to eliminating ROS, inhibiting inflammatory response, saving cell apoptosis, accelerating the adhesion and proliferation of neurons, and promoting the differentiation of neural stem cells into neurons. It is noteworthy that the FFFGHK hydrogel exhibits a promising therapeutic effect in the treatment of SCI in rats. This has been shown to significantly enhance the recovery of autonomic motor functions and signal transduction, as well as promote neuronal regeneration at the SCI site in these animals. This work presents a single-component peptide self-assembled supermolecular hydrogel system, incorporating the bioactive peptide GHK in conjunction with phenylalanine. It offers critical insights into the design of peptide-based supermolecular hydrogels for bioactive applications. STATEMENT OF SIGNIFICANCE.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144982022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanotherapy: Modulating immune cell function in tissue regeneration and fibrosis.","authors":"Niamh A Ward, Hannah Prendeville, Eimear J Wallace, Parand Shokrani, Lesley Trask, Rachael Dillon, Rachel Beatty, Ellen T Roche, Garry P Duffy, Eimear B Dolan","doi":"10.1016/j.actbio.2025.08.048","DOIUrl":"10.1016/j.actbio.2025.08.048","url":null,"abstract":"<p><p>Mechanotherapy - therapy which uses mechanical forces to produce a remedial or prophylactic effect - has great potential to improve therapeutic outcomes in the fields of regenerative medicine and drug delivery due to its adaptable and tunable nature. In particular, numerous in vivo studies have demonstrated the ability of mechanotherapies to improve functional muscle regeneration and modulate fibrosis. However, the cellular interactions that underlie these tissue level responses are poorly understood. To further harness the potential of mechanotherapies and inform their design and development, a more comprehensive understanding of immune cell responses to mechanical loading is required. Here, we review findings from preclinical investigations of mechanotherapies as both a treatment for muscular injury and as an immunomodulating component of medical implants. We then discuss the mechanosensitive nature of immune cells, emphasizing how mechanical loading and microenvironmental stresses can influence immune signalling pathways in the context of tissue regeneration and fibrosis. Finally, we offer our perspective on the future of the field, including the challenges facing mechanotherapeutic device development and the potential to further broaden the therapeutic targets of mechanotherapies. STATEMENT OF SIGNIFICANCE: Tissue regeneration following injury requires precise regulation of the innate and adaptive immune responses to restore tissue function and prevent fibrosis. Fibrotic tissue alters mechanical properties and impairs physiological function, making fibrosis a critical barrier to effective healing. Mechanotherapy, which uses mechanical forces for therapeutic effect, offers a promising approach to modulate immune responses and improve regenerative outcomes. Emerging evidence suggests that mechanical stimulation can attenuate fibrosis, yet the immune response to mechanical loading is highly dependent on loading parameters such as magnitude, frequency, and duration. Understanding how these parameters influence healing remains a key challenge. This review explores the relationship between mechanotherapy, immune modulation, and fibrosis, highlighting the potential for mechanotherapy to guide wound healing and improve clinical outcomes.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144982139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of scaffold material choice on osteosarcoma phenotype and drug responses in 3D.","authors":"Callan E Monette, Jeehee Lee, Abena Peasah, Leanne C Sayles, Michelle Tai, E Alejandro Sweet-Cordero, Fan Yang","doi":"10.1016/j.actbio.2025.08.046","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.08.046","url":null,"abstract":"<p><p>Biomaterials-based 3D models have emerged as new cancer research tools for studying osteosarcoma (OS). However, the impact of scaffold material choice on OS phenotype and drug responses in 3D remains largely unknown, as previous studies used different biomaterials as scaffolds without direct comparison. In this study, we systematically compared four biomaterials: Gelatin methacrylate (GelMA), Gelatin microribbons (Gel µRB), Collagen I hydrogel (Col1), and Poly(DL-lactide-co-glycolide) (PLGA). All have previously been applied for either 3D OS culture or bone tissue engineering. To mimic the mineral component of bone, hydroxyapatite mineral nanoparticles (HAnp) were incorporated into all scaffolds. We assessed key clinically relevant OS phenotypes including cell proliferation, extracellular matrix (ECM) deposition, and responses to multiple chemotherapeutic agents. Our results demonstrate that scaffold material significantly influences OS phenotype and drug resistance. Notably, PLGA results in the lowest cell proliferation, GelMA promotes drug resistance and tumor ECM deposition, and Gel µRB better mimics OS signaling of orthotopic tumor xenografts in vivo. The findings from this comparative study underscore the impact of scaffold choice on OS phenotype and drug response. It also provides valuable insights for guiding the selection of appropriate scaffold materials to better mimic the desirable OS phenotype to advance OS therapeutic discovery. STATEMENT OF SIGNIFICANCE: Osteosarcoma (OS), a highly aggressive bone cancer, has seen a stagnant survival rate for over three decades. This study addresses a critical knowledge gap by comparing four widely used bone tissue engineering scaffolds for 3D OS culture. Unlike previous studies, this work provides a comprehensive analysis of how scaffold choice influences OS proliferation, signaling, extracellular matrix deposition, and drug resistance. These findings underscore the critical role of biomaterials choice in modulating OS behavior and will guide the choice of 3D scaffolds for more effective OS disease modeling and improving therapeutic discovery.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144981998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Label-free structural and mechanical characterization of rat uterosacral ligaments.","authors":"Joseph Thomas, Kandace Donaldson, Clara Gimenez, Monique Vaughan, Yizheng Zhu, Raffaella De Vita","doi":"10.1016/j.actbio.2025.08.009","DOIUrl":"10.1016/j.actbio.2025.08.009","url":null,"abstract":"<p><p>This study presents quantitative applications of label-free imaging methods to characterize the structure of the uterosacral ligaments (USLs) before, during, and after loading. Rat USLs (n=14) were excised with their spinal and cervical attachments, clamped at these attachment sites, and pulled uniaxially in a custom-built tensile testing machine along their main in vivo loading direction. During uniaxial testing, optical coherence tomography (OCT) images were recorded, revealing the re-arrangement and failure of the structural components of the USLs. Before and after uniaxial testing, second harmonic generation (SHG) microscopy was also used to image collagen and smooth muscle within the proximal, intermediate, and distal regions of the USLs. From the OCT images, two metrics, the global depth variation (GDV) and the bundle energy projection (BEP), were extracted to quantify morphological changes as a function of the applied load and displacement. The GDV metric measured the heterogeneity of the USLs, while the BEP metric quantified the re-orientation of fiber bundles under uniaxial testing. SHG images showed that the rat USLs have a complex microstructure with wavy collagen fibers interwoven with smooth muscle bundles. These findings on the structure-function relationship of USLs may have implications for developing non-invasive, label-free imaging modalities suitable for diagnosing conditions such as pelvic organ prolapse (POP) by evaluating the structural integrity of USLs. Novelty and Significance Statement: The uterosacral ligaments (USLs), often compromised in pelvic organ prolapse (POP), are the primary support to the uterus and vagina, yet surgeries to restore their function frequently have poor outcomes. Non-invasive diagnostic tools are needed to assess the integrity of the USLs for treatment planning and monitoring. This study examines how the morphology of the USLs changes under mechanical loading, using optical coherence tomography (OCT) for detailed three-dimensional imaging and quantitative optical parameters that correlate morphology with load. Complementary second harmonic generation (SHG) microscopy reveals the organization of smooth muscle and collagen within the tissue structure. These label-free imaging techniques may enable the real-time, noninvasive assessment of tissue integrity and hold potential for future applications in improving the diagnosis and treatment of POP.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144982089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Invasive cancer cells soften collagen networks and disrupt stress-stiffening via volume exclusion, contractility and adhesion.","authors":"Irène Nagle, Margherita Tavasso, Ankur D Bordoloi, Iain A A Muntz, Gijsje H Koenderink, Pouyan E Boukany","doi":"10.1016/j.actbio.2025.08.036","DOIUrl":"10.1016/j.actbio.2025.08.036","url":null,"abstract":"<p><p>Collagen networks form the structural backbone of the extracellular matrix in both healthy and cancerous tissues, exhibiting nonlinear mechanical properties that crucially regulate tissue mechanics and cell behavior. Here, we investigate how the presence of invasive breast cancer cells (MDA-MB-231) influences the polymerization kinetics and mechanics of collagen networks using bulk shear rheology and rheo-confocal microscopy. We show that embedded cancer cells delay the onset of collagen polymerization due to volume exclusion effects. During polymerization, the cells (at 4% volume fraction) cause an unexpected time-dependent softening of the network. We show that this softening effect arises from active remodeling via adhesion and contractility rather than from proteolytic degradation. At higher cell volume fractions, the dominant effect of the cells shifts to volume exclusion, causing a two-fold reduction of network stiffness. Additionally, we demonstrate that cancer cells suppress the characteristic stress-stiffening response of collagen. This effect (partially) disappears when cell adhesion and contractility are inhibited, and it is absent when the cells are replaced by passive hydrogel particles. These findings provide new insights into how active inclusions modify the mechanics of fibrous networks, contributing to a better understanding of the role of cells in the mechanics of healthy and diseased tissues like invasive tumors. STATEMENT OF SIGNIFICANCE: Understanding how cells influence tissue mechanics is crucial to unravel disease progression. While fibroblasts are known to stiffen tissues, the role of invasive cancer cells is less clear. Using collagen-based tissue models, we reveal that cancer cells unexpectedly soften the collagen matrix and disrupt its stress-stiffening response. By comparing active cells to passive particles and selectively blocking cell functions, we show that volume exclusion, adhesion, and contractility each play distinct roles in shaping tissue mechanics. This work sheds light on the physical impact of cancer cells on their environment, advancing our understanding on how cells dynamically alter the mechanical properties of tissues.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144982066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toward preclinical evaluation of a thermosensitive PEG-poly(_L-alanine) hydrogel: A study on sterilization, storage stability, and in vivo performance.","authors":"Xin Wang, Zhiyong Chen, Zixuan Wang, Liwei Zhang, Jiandong Ding, Lin Yu","doi":"10.1016/j.actbio.2025.08.042","DOIUrl":"10.1016/j.actbio.2025.08.042","url":null,"abstract":"<p><p>Poly(amino acid)-based thermosensitive hydrogels hold great potential for clinical translation. Herein, we employ a thermosensitive methoxy poly(ethylene glycol)-block-poly(_L-alanine) (mPEG-PAla) hydrogel that undergoes a sol-to-gel transition upon heating as the model system to systematically evaluates its sterilizability, storage stability, in vivo degradation and in vivo drug release profiles-critical factors for clinical translation. mPEG-PAla copolymers are synthesized via ring-opening polymerization using the optimized amount of crown ether as the catalyst, ensuring controlled polymerization while minimizing catalyst usage. The powder form of the synthesized polymer facilitates efficient UV irradiation sterilization, and its aqueous solution can be rapidly prepared within 15 min. When pre-loaded into syringes, the mPEG-PAla hydrogel demonstrates storage stability for over 6 months. After subcutaneous injection into mice, traditional anatomic observation combined with nondestructive fluorescence imaging and magnetic resonance imaging (MRI) confirms that the mPEG-PAla hydrogel exhibits a stable in vivo degradation pattern, persisting for over 1.5 months, and its degradation products are metabolized primarily by the liver and kidneys. Histological analysis and MRI further validate the good biocompatibility of hydrogel. Fluorescence imaging reveals that the in vivo release profiles of three distinct fluorescent molecules, used as model drugs, present significant differences but follow the first-order release kinetics. STATEMENT OF SIGNIFICANCE: Intelligent hydrogels have garnered significant attention for various biomedical applications. Nevertheless, few have entered clinical practice, and their successful clinical translation depends on fundamental research related to effective sterilization, long-term storage stability, and in vivo fate estimation. In this study, we systematically evaluated the translation potential of an injectable and thermosensitive mPEG-PAla hydrogel by optimizing the synthesis of mPEG-PAla copolymer and validating its sterilization efficacy, convenience of preparation, storage stability, in vivo degradation and in vivo drug release profiles. This study enhances the understanding of PEG-poly(amino acid) hydrogels and provides valuable insights for their preclinical studies and future applications.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144982215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro and in vivo degradation behavior of an assembled magnesium alloy suture anchor for ligament-bone reconstruction.","authors":"Delin Ma, Zhaotong Sun, Qichao Zhao, Yuan Zhang, Wancheng Li, Jie Wang, Yijing Chen, Minghui Zhao, Jun Wang, Junfei Huang, Wenxiang Li, Shijie Zhu, Liguo Wang, Xiaochao Wu, Shaokang Guan","doi":"10.1016/j.actbio.2025.08.019","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.08.019","url":null,"abstract":"<p><p>Biodegradable magnesium alloys suture anchors face rapid anchor eyelet degradation, compromising mechanical strength. In this study, an assembled-structure magnesium alloy suture anchor was proposed to mitigate the fast failure of anchor eyelet. In vitro and in vivo experiments were conducted to evaluate the degradation behavior and biomechanical performance of assembled ZE21C magnesium alloy suture anchors. In vitro, mechanical tests revealed stable fixation with a pull-out force of 123.1 ± 5.9 N and fracture strength of 213.3 ± 3.6 N, ensuring no risk of anchor breakage under physiological loads. Immersion in Hanks' solution demonstrated the screw and tail regions degraded progressively over 14 days, while the anchor eyelet retained structural integrity. The in vivo degradation behavior mirrored in vitro findings and suture anchor maintained its mechanical integrity for 12 weeks post-surgery. Micro-CT and histological analyses confirmed successful functional recovery and fibrocartilage regeneration at the ligament-bone interface. Gas cavities observed post-implantation resolved by week 12 without anchor dislocation. The rapid degradation of threaded region released magnesium ions to facilitate osteogenesis, while the slower degradation of anchor eyelet maintained structural integrity for stable fixation. The gradual decline in fracture force of eyelet parts remained higher than the initial pull-out force within 12 weeks implantation. Furthermore, progressive integration occurred in the connection of assembled anchor further highlighted its reliable fixation performance. This study offers a framework for further design and research of biodegradable magnesium alloy suture anchors for clinical applications. STATEMENT OF SIGNIFICANCE: Achieving clinical efficacy for biodegradable magnesium alloy anchors requires maintaining long-term mechanical stability post-surgery. Delaying degradation at suture-contact anchor eyelet can prolong service life. In this study, we designed an assembled anchor with external full threads to enhance fixation strength while preventing body fluid infiltration into internal anchor eyelet to retard its degradation. Multi-scale in vitro/vivo studies revealed that rapid degradation of external threads promoted bone-tissue integration, whereas slower-degrading anchor eyelet preserved structural stability. Notably, the fracture strength at 12 weeks post-implantation remained superior to the initial pull-out strength. These findings demonstrate the potential for broadening clinical applications of magnesium alloy anchors in future trials.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144981962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}