Acta biomaterialia最新文献

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BaTiO3-based piezoelectric wireless neuromodulation: From molecular mechanisms to clinical translation challenges. 基于batio3的压电无线神经调节:从分子机制到临床翻译挑战。
IF 9.6
Acta biomaterialia Pub Date : 2026-10-02 DOI: 10.1016/j.actbio.2026.10.003
Xuetong Xu, Tianhui Wu, Yan Huang, Tianyu Sun, Yuxi Li, Weiwei Cao, Chaoya Xue, Miao Zhang
{"title":"BaTiO<sub>3</sub>-based piezoelectric wireless neuromodulation: From molecular mechanisms to clinical translation challenges.","authors":"Xuetong Xu, Tianhui Wu, Yan Huang, Tianyu Sun, Yuxi Li, Weiwei Cao, Chaoya Xue, Miao Zhang","doi":"10.1016/j.actbio.2026.10.003","DOIUrl":"https://doi.org/10.1016/j.actbio.2026.10.003","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Neurological injuries remain difficult to treat due to the complex microenvironment and the limited intrinsic regenerative capacity of neural tissues. Recently, wireless neuromodulation based on piezoelectric nanomaterials, particularly barium titanate (BaTiO&lt;sub&gt;3&lt;/sub&gt;), has emerged as a promising alternative to conventional implantable electrical stimulation. Polar BaTiO&lt;sub&gt;3&lt;/sub&gt; ceramics generally have higher piezoelectric charge coefficients than conventional Polyvinylidene Fluoride (PVDF) and Poly(vinylidene fluoride-co-trifluoroethylene) (P(VDF-TrFE)) films, are more resistant to degradation than ZnO, and are lead-free unlike Lead Zirconate Titanate (PZT), although their rigidity and potential persistence in tissue complicate soft-tissue integration and post-treatment clearance. This review systematically summarizes recent advances in BaTiO&lt;sub&gt;3&lt;/sub&gt;-enabled piezoelectric neuromodulation and further outline preclinical applications in pain management and metabolic regulation across multiple neurological disorders, including traumatic brain injury (TBI), spinal cord injury (SCI), peripheral nerve injury (PNI), and post-traumatic epilepsy (PTE). We subsequently analyze the underlying mechanisms for neural repair, highlighting modulation of voltage-gated ion channels (e.g., Ca&lt;sup&gt;2+&lt;/sup&gt; and Na&lt;sup&gt;+&lt;/sup&gt;) to regulate neuronal excitability and stem cell differentiation, mitochondrial targeting to influence metabolism and immune polarization, and controlled intracellular ion release (e.g., Zn&lt;sup&gt;2+&lt;/sup&gt;) to modulate gene transcription. To enhance electromechanical-biological coupling in vivo, interface engineering strategies for BaTiO&lt;sub&gt;3&lt;/sub&gt; are also discussed, with emphasis on surface modification approaches such as polydopamine functionalization and integration with conductive hydrogels to improve biomechanical compatibility. Finally, key challenges for clinical translation, including the lack of standardized stimulation parameters, are addressed, providing insights for the development of next-generation neuromodulation-based therapies. STATEMENT OF SIGNIFICANCE: Neurological injuries and diseases represent some of the most formidable clinical challenges because neural tissues have limited regenerative capacity, whereas conventional wired electrical stimulation is invasive. Although BaTiO&lt;sub&gt;3&lt;/sub&gt;-based piezoelectric nanomaterials have emerged as important wireless transducers for neuromodulation, the field still lacks a systematic framework linking the fundamental electromechanical properties of BaTiO&lt;sub&gt;3&lt;/sub&gt; to disease-relevant therapeutic mechanisms and barriers to clinical translation. This review provides a systematic, mechanism-oriented assessment of BaTiO&lt;sub&gt;3&lt;/sub&gt;-based wireless neuromodulation by outlining its crystallographic basis and multiscale structural engineering and examining how localized electrical potentials may modulate voltage-gated ion channels, the neuroimmune microenvironment, and stem-c","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149119977","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}
引用次数: 0
Proteolysis-programmed reopening of bilayer hydrogel actuators. 蛋白水解-双层水凝胶驱动器的程序化重开。
IF 9.6
Acta biomaterialia Pub Date : 2026-10-01 DOI: 10.1016/j.actbio.2026.09.055
Fan Mo, Gali Bar-Shalom, Tina Khairallah, Ehud Shimko Gozlan, Yuchen Liu, Alejandro Sosnik, Luai R Khoury
{"title":"Proteolysis-programmed reopening of bilayer hydrogel actuators.","authors":"Fan Mo, Gali Bar-Shalom, Tina Khairallah, Ehud Shimko Gozlan, Yuchen Liu, Alejandro Sosnik, Luai R Khoury","doi":"10.1016/j.actbio.2026.09.055","DOIUrl":"10.1016/j.actbio.2026.09.055","url":null,"abstract":"<p><p>Soft hydrogel actuators that interface with living tissues must combine reliable attachment with programmed disengagement after completing their function. Here, we introduce a programmed-reopening bilayer hydrogel actuator with an intrinsic material off-switch. Using multilayer digital light processing (DLP), we fabricate poly(N-isopropylacrylamide)/bovine serum albumin-poly(ethylene glycol) diacrylate(Trypsin) (PNIPAM/BSA-PEGDA(Trypsin)) bilayers in which the PNIPAM layer drives closure at physiological temperature (37 °C), while the trypsin-loaded BSA-PEGDA layer undergoes proteolysis-programmed softening. The progressive loss of stiffness relaxes curvature and reopens the device. We quantify print-parameter-dependent actuation, trypsin encapsulation and release, retained proteolytic activity, and time-dependent softening of the enzyme-programmed layer. Lap-shear testing and microscopy characterize the bonded bilayer interface. Mechanistic anchoring is visualized on a mucin-mimicking interface by microscopy and time-lapse imaging, and ex vivo tests on porcine small intestine demonstrate robust retention under controlled dynamic motion with millinewton-scale gripping forces. These findings establish a materials strategy for programming the functional lifetime and reopening of tissue-interfacing hydrogel actuators. STATEMENT OF SIGNIFICANCE: Tissue-interfacing hydrogel actuators are promising for gastrointestinal retention and local therapy, but most existing systems deform in one direction and lack an intrinsic mechanism for disengagement. We introduce a programmed-reopening bilayer actuator in which proteolysis-programmed mechanical relaxation acts as an internal off-switch. Multilayer digital light processing (DLP) produces poly(N-isopropylacrylamide)/bovine serum albumin-poly (ethylene glycol) diacrylate (Trypsin) (PNIPAM/BSA-PEGDA(Trypsin)) bilayers that close at physiological temperature, release active trypsin, and progressively reopen as the protein-polymer layer softens. The study integrates release, mechanical relaxation, preliminary cytocompatibility, mucin-mimicking interface anchoring, and ex vivo retention on porcine small intestine. It establishes a materials design principle for programming actuator lifetime and termination, advancing autonomous and transient soft biomedical devices.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149120107","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}
引用次数: 0
Spatio-temporal mechanosensitive phagocytic response of retinal pigment epithelial cells to reversible changes in substrate stiffness. 视网膜色素上皮细胞对基质硬度可逆变化的时空机械敏感性吞噬反应。
IF 9.6
Acta biomaterialia Pub Date : 2026-10-01 DOI: 10.1016/j.actbio.2026.09.053
Colleen M Simmerly, Mohammad Aminul Islam, Adam P Williamson, Elise A Corbin
{"title":"Spatio-temporal mechanosensitive phagocytic response of retinal pigment epithelial cells to reversible changes in substrate stiffness.","authors":"Colleen M Simmerly, Mohammad Aminul Islam, Adam P Williamson, Elise A Corbin","doi":"10.1016/j.actbio.2026.09.053","DOIUrl":"10.1016/j.actbio.2026.09.053","url":null,"abstract":"<p><p>In aging and diseased retina, Bruch's membrane (BrM) stiffens heterogeneously, impairing phagocytic clearance of photoreceptor outer segments by the overlying retinal pigment epithelial (RPE) monolayer and contributing to retinal degeneration. While substrate stiffness is known to influence RPE phagocytosis, conventional assays lack the spatial resolution to capture how mechanical cues coordinate behavior across the monolayer over time. Here, dynamic magnetorheological elastomer (MRE) substrates are combined with an automated machine-learning image-analysis pipeline to simultaneously quantify particle engagement kinetics, cell morphology, and spatial organization at single-cell resolution. This combination enables spatiotemporal observation of RPE mechanosensitivity inaccessible to population-level assays. Substrate stiffness shaped particle engagement kinetics, modulating engagement rate and maximum particle capacity. Soft substrates additionally increased cell area and eccentricity, suggesting stiffness-dependent cytoskeletal remodeling. Strikingly, cells with increased levels of particle engagement form spatially localized clusters whose organization was sensitive to substrate stiffness, revealing that mechanical cues coordinate engagement behavior at the tissue level rather than acting on cells independently. This work reveals how dynamic BrM stiffening drives coupled changes in particle engagement kinetics, cell morphology, and spatial coordination, highlighting the tissue-level complexity of RPE mechanosensitivity. Together, these findings reframe RPE particle engagement as a spatially coordinated, mechanosensitive process, providing new insight into how dynamic alterations in extracellular mechanical environments regulate cellular function. STATEMENT OF SIGNIFICANCE: The retinal pigment epithelium (RPE) clears cellular debris daily to maintain vision, a process that falters as the underlying tissue stiffens with age, a hallmark of macular degeneration. Existing tools capture only population averages on static surfaces, obscuring both the timing and spatial organization of the response. This study combines dynamically tunable substrates with automated machine-learning image analysis to quantify receptor-mediated particle engagement at single-cell resolution across time and space. Mechanical transitions, not stiffness magnitude alone, accelerate engagement rate while reducing total capacity. Cell shape predicts particle engagement activity in a stiffness-dependent manner, and highly active cells cluster spatially in patterns governed by the mechanical environment. These findings reframe RPE dysfunction as a spatially coordinated, mechanosensitive process with direct implications for early AMD.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13674358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149120032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cooperative poly(ethylene glycol) dehydration and ion-dependent electrostatic interactions drive thermally irreversible polyion complex flower micelle hydrogels. 协同聚乙二醇脱水和离子依赖的静电相互作用驱动热不可逆多离子复合物花胶束水凝胶。
IF 9.6
Acta biomaterialia Pub Date : 2026-10-01 DOI: 10.1016/j.actbio.2026.09.056
Sho Sakaue, Aiki Marushima, Yukio Nagasaki
{"title":"Cooperative poly(ethylene glycol) dehydration and ion-dependent electrostatic interactions drive thermally irreversible polyion complex flower micelle hydrogels.","authors":"Sho Sakaue, Aiki Marushima, Yukio Nagasaki","doi":"10.1016/j.actbio.2026.09.056","DOIUrl":"https://doi.org/10.1016/j.actbio.2026.09.056","url":null,"abstract":"<p><p>Thermoresponsive hydrogels based on flower-micelle assemblies that undergo gelation upon heating are attractive as injectable soft materials. We previously reported that Redox Injectable Gels (RIGs), formed from polyion complex (PIC) flower micelles, exhibit unusually high stiffness together with thermally irreversible gelation. Here, we investigate the physicochemical basis of this distinctive behavior by systematically examining the effects of phosphate buffer concentration and salt species on gelation dynamics, micellar structure, and segmental mobility. Rheological analyses showed that gelation accelerated with increasing buffer concentration, whereas the maximum storage modulus exhibited a nonmonotonic dependence, reaching a minimum at intermediate ionic conditions. Salt addition further modulated gel stiffness in an ion- and concentration-dependent manner, consistent with an ionic window in which moderate electrostatic screening alters electrostatic complexation within PIC cores and may facilitate micellar reorganization, whereas excessive screening at higher ionic strengths suppresses network reinforcement. Complementary dynamic light scattering (DLS), proton nuclear magnetic resonance (<sup>1</sup>H NMR), fluorescence quenching, and pyrene solvatochromism collectively indicate that poly(ethylene glycol) (PEG) dehydration-consistent with cloud-point depression under high ionic strength-together with ion-dependent modulation of electrostatic interactions contributes to micelle reorganization and network formation. Collectively, these findings support a cooperative mechanistic framework in which PEG dehydration and ion-dependent modulation of electrostatic interactions jointly contribute to the robust and thermally irreversible gelation of RIGs. This framework provides design principles for tuning ionic environments to engineer mechanically robust thermoresponsive injectable hydrogels for biomedical applications under physiologically relevant ionic conditions. STATEMENT OF SIGNIFICANCE: Thermoresponsive injectable hydrogels are attractive biomaterials, but conventional flower-micelle systems typically exhibit weak mechanical properties and thermoreversible gelation. This study clarifies why redox injectable gels (RIGs), formed from polyion complex flower micelles, exhibit unusually high stiffness together with thermally irreversible gelation. By systematically varying buffer concentration and salt species, we show that gelation is strongly influenced by poly(ethylene glycol) (PEG) dehydration and ion-dependent modulation of electrostatic interactions within PIC micelles. These findings support a cooperative mechanistic framework for understanding salt- and buffer-dependent gelation and provide design principles for developing mechanically robust injectable biomaterials under physiologically relevant ionic environments.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149119952","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}
引用次数: 0
Thermosensitive hydroxypropyl chitin-based hydrogel for trigeminal neuralgia: Rapid analgesia, myelin repair, and attenuation of gamma-band hyperactivity in the spinal trigeminal nucleus caudalis. 热敏羟丙基几丁质水凝胶治疗三叉神经痛:快速镇痛、髓鞘修复和减弱三叉脊髓尾核γ带亢进。
IF 9.6
Acta biomaterialia Pub Date : 2026-10-01 DOI: 10.1016/j.actbio.2026.09.051
Haoxin Liu, Xin Guo, Zhiqiang Li, Taotao Li, Wenjie Shi, Xiaoying Li, Yuyang Xiao, Ze Li, Xuan Dai, Bangkun Yang, Songshan Chai, Sen Ren, Yuankun Cai, Lei Pei, Nanxiang Xiong, Xulin Jiang
{"title":"Thermosensitive hydroxypropyl chitin-based hydrogel for trigeminal neuralgia: Rapid analgesia, myelin repair, and attenuation of gamma-band hyperactivity in the spinal trigeminal nucleus caudalis.","authors":"Haoxin Liu, Xin Guo, Zhiqiang Li, Taotao Li, Wenjie Shi, Xiaoying Li, Yuyang Xiao, Ze Li, Xuan Dai, Bangkun Yang, Songshan Chai, Sen Ren, Yuankun Cai, Lei Pei, Nanxiang Xiong, Xulin Jiang","doi":"10.1016/j.actbio.2026.09.051","DOIUrl":"https://doi.org/10.1016/j.actbio.2026.09.051","url":null,"abstract":"<p><p>Trigeminal neuralgia is a debilitating neuropathic disorder characterized by the complex interplay of peripheral demyelination and central sensitization. Current pharmacotherapies remain palliative, limited by systemic toxicity and an inability to reverse pathological microenvironments. Herein, an injectable hydrogel integrating analgesic and nerve-repair functions is engineered using thermosensitive hydroxypropyl chitin (HPCH) and oxidized chondroitin sulfate (OCS) to encapsulate microcrystalline carbamazepine (CBZ) for targeted neuro-restoration. Upon perineural injection, the hydrogel precursor undergoes a swift in situ sol-gel transition via dual-crosslinking network formation, intimately enveloping injured nerve fibers to create a stable, bioactive depot. This system executes a spatiotemporally coordinated biphasic intervention: rapid CBZ release provides immediate analgesia by blocking voltage-gated sodium channels, while the bioactive OCS matrix subsequently remodels the local inflammatory microenvironment, downregulating pro-inflammatory cytokines, and guides prolonged regeneration of compact myelin sheaths, which may help restore peripheral nerve insulation and reduce ephaptic transmission. Crucially, in vivo local field potential recordings in the spinal trigeminal nucleus caudalis demonstrate that CBZ@HPCH/OCS treatment attenuated injury-associated gamma-band (30-80 Hz) hyperactivity. This multimodal paradigm integrates rapid pharmacological inhibition with sustained biological repair to effectively alleviate neuropathic pain with no obvious treatment-associated histopathological abnormalities observed in the examined major organs at 14 days post-treatment. STATEMENT OF SIGNIFICANCE: Trigeminal neuralgia causes excruciating facial pain, yet current oral treatments often provide only temporary relief while causing significant systemic toxicity. This study introduces an injectable hydrogel integrating analgesic and nerve-repair functions that transitions from liquid to solid at body temperature for targeted therapy. Unlike traditional drugs that merely mask symptoms, this dual-action system delivers immediate analgesia while actively repairing damaged myelin sheaths. This structural restoration effectively attenuated injury-associated gamma-band hyperactivity and alleviated neuropathic pain. By integrating rapid pharmacological action with long-term biological repair, this work offers a localized, low-toxicity paradigm for chronic pain management, representing a significant advance for researchers in biomaterials, neuroscience, and clinical pain therapy.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149120070","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}
引用次数: 0
An injectable hydrogel sustains low-dose intra-articular glucocorticoid exposure to protect cartilage in osteoarthritis. 一种可注射的水凝胶维持低剂量的关节内糖皮质激素暴露以保护骨关节炎的软骨。
IF 9.6
Acta biomaterialia Pub Date : 2026-09-30 DOI: 10.1016/j.actbio.2026.09.049
Xiaoyue Li, Dong Zhu, Jingyu Zhang, Jing Lyu, Chunyu Zhao, Lucy Boyi Wang, Peisheng Jin, Rijian Song, Qiang Li, Wenxin Wang
{"title":"An injectable hydrogel sustains low-dose intra-articular glucocorticoid exposure to protect cartilage in osteoarthritis.","authors":"Xiaoyue Li, Dong Zhu, Jingyu Zhang, Jing Lyu, Chunyu Zhao, Lucy Boyi Wang, Peisheng Jin, Rijian Song, Qiang Li, Wenxin Wang","doi":"10.1016/j.actbio.2026.09.049","DOIUrl":"https://doi.org/10.1016/j.actbio.2026.09.049","url":null,"abstract":"<p><p>Intra-articular glucocorticoid (GC) injections provide rapid symptomatic relief in osteoarthritis (OA). However, repeated administration of conventional triamcinolone acetonide (TA) suspensions can generate recurrent high local drug exposure, which may contribute to cartilage degeneration. Although extended-release TA formulations have been developed to reduce burst exposure, achieving prolonged and stable intra-articular drug retention while preserving cartilage structure remains challenging. Here we report an injectable hyaluronic acid (HA) hydrogel that forms a stable intra-articular depot to sustain delivery of TA and control local GC exposure kinetics. Sustained low-dose GC exposure modulates macrophage-associated inflammatory responses, suppresses pro-inflammatory cytokine production, and preserves chondrocyte mitochondrial homeostasis under inflammatory stress. In both murine and load-bearing large animal goat OA models, TA-loaded HA hydrogel treatment improves functional performance, reduces synovial inflammation, and preserves cartilage structure and matrix integrity, as demonstrated by enhanced gait or mechanical pain thresholds and higher MRI-based MOCART 2.0 scores. Our findings indicate that tuning intra-articular GC pharmacokinetics can enhance therapeutic durability while promoting structural joint preservation in OA. STATEMENT OF SIGNIFICANCE: Intra-articular glucocorticoids are widely used in osteoarthritis, yet their clinical value is limited by rapid clearance, repeated dosing, and harmful peak exposure. This work introduces an injectable hyaluronic acid hydrogel that transforms glucocorticoid therapy from a short-lived anti-inflammatory injection into a controlled, cartilage-protective treatment. By establishing a stable intra-articular drug depot, the hydrogel reshapes local glucocorticoid exposure, suppresses destructive joint inflammation, promotes a reparative microenvironment, and preserves chondrocyte and matrix homeostasis. Importantly, these benefits were demonstrated not only in mice but also in a load-bearing goat model, highlighting a clinically relevant biomaterial strategy for safer and more durable structure-modifying osteoarthritis therapy.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149119985","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}
引用次数: 0
Flowable and microporous granular grafts made from decellularized extracellular matrix microgels for tissue repair. 由脱细胞细胞外基质微凝胶制成的可流动和微孔颗粒移植物,用于组织修复。
IF 9.6
Acta biomaterialia Pub Date : 2026-09-29 DOI: 10.1016/j.actbio.2026.09.047
Muhammad Maaz Khurram, Keira Vesy, Jun Kim, Tuba Marjan, Mihika Desai, Dean Stornello, Taimoor H Qazi
{"title":"Flowable and microporous granular grafts made from decellularized extracellular matrix microgels for tissue repair.","authors":"Muhammad Maaz Khurram, Keira Vesy, Jun Kim, Tuba Marjan, Mihika Desai, Dean Stornello, Taimoor H Qazi","doi":"10.1016/j.actbio.2026.09.047","DOIUrl":"10.1016/j.actbio.2026.09.047","url":null,"abstract":"<p><p>Decellularized extracellular matrix (dECM) scaffolds are widely used in tissue engineering, primarily due to their inherent bioactivity and cell-instructive properties. ECM scaffolds are conventionally prepared as monolithic and rigid sheet-like constructs and while these form factors are generally sutured at the defect site, it can be challenging to achieve even filling of the defect volume, where flowable scaffolds may be beneficial. Although infusible and injectable dECM formulations have been developed, optimizing for high mechanical strength and a porous microstructure that permits integration with host tissue remains difficult. Here, we report the fabrication of granular dECMs, which are flowable and microporous biomaterials that are assembled through the packing of crosslinked dECM microgels. A feature of these dECM microgels is their crosslinking through dityrosine photochemistry, which circumvents the need for chemical modification of the dECM with synthetic functional groups. Granular dECMs show tunable porosity through optimization of microgel packing, and shear-responsive rheological behaviors that impart extrudability from syringe needles. When tested in a mouse model of volumetric muscle loss and compared against no treatment negative controls, bioinert granular controls made with poly(ethylene glycol) diacrylate, and bulk dECM implants, granular dECMs showed improved wound healing properties and support robust angiogenesis and myogenesis at a structural level. Data from longitudinal muscle force measurements carried out over 12 weeks showed comparable levels of functional recovery across all groups. Collectively, these results showcase the potential promise of dityrosine crosslinked granular dECMs as acellular injectable grafts for reconstructive surgery and wound healing applications. STATEMENT OF SIGNIFICANCE: Acellular biomaterial grafts made with decellularized tissues are commercially available and clinically used for reconstructive and wound healing applications. Their rigid design and low malleability has motivated the development of injectable and infusible dECM hydrogels. However, it has remained challenging to co-optimize their mechanical properties and microporosity for tissue repair applications. This work presents a granular dECM graft technology that uses light-activated crosslinking of tyrosine groups naturally present in protein-rich tissues to fabricate dECM microgels that are then assembled into microporous scaffolds that flow under strain and can be extruded via syringe into irregularly shaped tissue defects. Using a clinically relevant mouse model of muscle injury, we highlight the regenerative potential of granular dECM grafts in supporting rapid vascularization and myogenesis at the defect site. This advanced design of injectable and flowable dECM biomaterials is likely to find broad utility in reconstructive surgery and tissue engineering applications.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149083187","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}
引用次数: 0
Multifunctional ROS-responsive bioprosthetic heart valves armored with a puerarin-loaded artificial-plasma hydrogel coating for concurrent thromboresistance and immunomodulation. 用葛根素负载的人工血浆水凝胶涂层包膜的多功能ros反应生物假心脏瓣膜,用于并发血栓抵抗和免疫调节。
IF 9.6
Acta biomaterialia Pub Date : 2026-09-29 DOI: 10.1016/j.actbio.2026.09.046
Yanchang Feng, Daisong Jiang, Lepeng Chen, Xueyu Huang, Cheng Zheng, Yunbing Wang
{"title":"Multifunctional ROS-responsive bioprosthetic heart valves armored with a puerarin-loaded artificial-plasma hydrogel coating for concurrent thromboresistance and immunomodulation.","authors":"Yanchang Feng, Daisong Jiang, Lepeng Chen, Xueyu Huang, Cheng Zheng, Yunbing Wang","doi":"10.1016/j.actbio.2026.09.046","DOIUrl":"10.1016/j.actbio.2026.09.046","url":null,"abstract":"&lt;p&gt;&lt;p&gt;The advent of minimally invasive transcatheter heart valve replacement has provided a low-risk therapeutic option for valvular heart disease, while driving the escalated clinical demand for bioprosthetic heart valves (BHVs). However, BHVs are susceptible to thrombosis, immunoinflammatory responses, and calcification owing to exposure of the prothrombotic and xenogeneic collagenous matrix and its interactions with the host immune system; these factors collectively accelerate degeneration and severely limit their clinical durability. Herein, a reactive oxygen species (ROS)-responsive artificial-plasma hydroxyethyl starch (HES) layer armored BHV (PUE@HES-GAPP) was constructed. A hydrophilic artificial-plasma coating based on HES was anchored on glutaraldehyde (GA)-crosslinked porcine pericardium substrate via photo-initiated radical polymerization. This artificial-plasma coating serves as a biocompatible physical barrier to shield the thrombogenic collagenous matrix and effectively inhibit platelet aggregation and nonspecific protein adhesion, significantly enhancing the BHVs' hemocompatibility and antithrombotic capacity. Meanwhile, it also served as a scaffold for endothelial cell adhesion and proliferation, improving the endothelialization potential of BHVs. Anti-inflammatory molecule puerarin (PUE) was further loaded onto the artificial-plasma layer surface via dynamic borate ester bonds, thereby achieving the on-demand release of PUE in the inflammatory microenvironment. PUE inhibits the NOD-like receptor, JAK-STAT, and NF-κ B signaling pathways, allowing for precise regulation of the immunoinflammatory responses on BHVs. Subcutaneous implantation experiments in rats confirmed that PUE@HES-GAPP exhibited superior anti-calcification performance at 12 weeks post-implantation. Collectively, the proposed ROS-responsive artificial-plasma modification strategy synergistically enhances the antithrombotic, immunoinflammatory modulation, anti-calcification, and pro-endothelialization properties of BHVs, which provides an innovative material design solution to address the structural degeneration risk of BHVs, holding significant potential for prolonging the lifespan of BHVs. STATEMENT OF SIGNIFICANCE: The clinical durability of BHVs is critically compromised by thrombosis, immunoinflammatory reactions, and pathological calcification, mainly attributed to the interactions between the exposed xenogeneic collagen matrix and the blood. A ROSresponsive artificial-plasma coating was covalently anchored onto the xenogeneic collagen matrix of BHVs to address these challenges. This artificial plasma-based coating serves as a blood-compatible barrier that significantly suppressed calcification, inhibited platelet adhesion and thrombosis, and supported endothelial cell adhesion and proliferation. Puerarin was loaded via ROS-responsive phenylboronic acid ester to achieve microenvironment-responsive on-demand release specifically under inflammatory conditions, ","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149083199","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}
引用次数: 0
Retraction notice to "Cobalt-mediated multi-functional dressings promote bacteria-infected wound healing" [Acta Biomaterialia 86 (2019) 465-479]. 关于“钴介导多功能敷料促进细菌感染伤口愈合”的撤回通知[生物材料学报86(2019)465-479]。
IF 9.6
Acta biomaterialia Pub Date : 2026-09-28 DOI: 10.1016/j.actbio.2026.09.036
Qingying Shi, Xin Luo, Ziqi Huang, Adam C Midgley, Bo Wang, Ruihua Liu, Dengke Zhi, Tingting Wei, Xin Zhou, Mingqiang Qiao, Jun Zhang, Deling Kong, Kai Wang
{"title":"Retraction notice to \"Cobalt-mediated multi-functional dressings promote bacteria-infected wound healing\" [Acta Biomaterialia 86 (2019) 465-479].","authors":"Qingying Shi, Xin Luo, Ziqi Huang, Adam C Midgley, Bo Wang, Ruihua Liu, Dengke Zhi, Tingting Wei, Xin Zhou, Mingqiang Qiao, Jun Zhang, Deling Kong, Kai Wang","doi":"10.1016/j.actbio.2026.09.036","DOIUrl":"10.1016/j.actbio.2026.09.036","url":null,"abstract":"","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149076960","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}
引用次数: 0
Stiffness by design in biological fibers: The influence of microstructure and temperature. 生物纤维设计的刚度:微观结构和温度的影响。
IF 9.6
Acta biomaterialia Pub Date : 2026-09-27 DOI: 10.1016/j.actbio.2026.09.037
Eli Yovel, Noy Cohen
{"title":"Stiffness by design in biological fibers: The influence of microstructure and temperature.","authors":"Eli Yovel, Noy Cohen","doi":"10.1016/j.actbio.2026.09.037","DOIUrl":"10.1016/j.actbio.2026.09.037","url":null,"abstract":"<p><p>Silk fibers exhibit unique mechanical properties such as high stiffness, toughness, and elasticity. The stiffness of silk fibers is governed by a hierarchical microstructure that is highly sensitive to the extraction method, post-processing, and environmental factors such as temperature. Commonly, the microstructure features an amorphous matrix comprising polypeptide chains that interact through weak intermolecular bonds and interconnect via crystalline domains. In this work, we develop a microscopically motivated energy-based model that provides fundamental insights into the underlying mechanisms governing the stiffness of silk fibers. The initial deformation is driven by (1) the entropic extension of polypeptide chains, (2) the elastic stretching and rotation of rigid crystalline domains, and (3) the distortion of weak intermolecular interactions, which lead to the relative sliding of polypeptide chains. The model quantitatively captures the influence of key physical microstructural quantities such as chain alignment, initial chain stretch, intermolecular bond strength, and crystallite size on the overall stiffness. The merit of the model is demonstrated through a comparison to spider silk and cocoon silk fibers. We also employ the model to better understand the influence of the reeling speed during the extraction of spider silk fibers on the microstructure and, consequently, on the stiffness. We follow with a parametric analysis that studies the influence of different microstructural quantities on the fiber stiffness. Lastly, the framework is extended to account for thermally-induced microstructural changes and the model predictions are compared to experimental data on the stiffness of cocoon silk fibers as a function of temperature. The findings from this work delineate the role of microstructure on the overall stiffness and offer a pathway for the efficient design of tunable and optimized biomimetic fibers for target applications. Statement of Significance: This work addresses a critical gap in the engineering of biological fibers by introducing a microscopically motivated, energy-based model that sheds light on the influence of key microstructural parameters on stiffness. By explicitly incorporating localized deformation kinematics and thermal effects, the model is used to capture the stiffness of diverse protein-based fibers, such as spider and cocoon silk, under different processing conditions and temperature regimes. This framework provides new insights into the role of key microstructural quantities on the overall stiffness, thereby paving the way to the design of tunable and optimized biomimetic fibers with targeted mechanical profiles that can be used in various applications.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149070759","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}
引用次数: 0
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