Bioactive MaterialsPub Date : 2025-04-23DOI: 10.1016/j.bioactmat.2025.04.021
Yanjiao Li , Bin Jiang , Zhen Wu , Zhaoxia Ma , Lihua Qiu , Wen Cui , Yunhui Zhao , Jinghe Yan , Daiping Ma , Xingfei Wu , Shu Liang , Sitao Wang , Yanqun Zhao , Mengting Wang , Min Hu
{"title":"Engineering fibroblast with reprogramming and spheronization for bone defect repair","authors":"Yanjiao Li , Bin Jiang , Zhen Wu , Zhaoxia Ma , Lihua Qiu , Wen Cui , Yunhui Zhao , Jinghe Yan , Daiping Ma , Xingfei Wu , Shu Liang , Sitao Wang , Yanqun Zhao , Mengting Wang , Min Hu","doi":"10.1016/j.bioactmat.2025.04.021","DOIUrl":"10.1016/j.bioactmat.2025.04.021","url":null,"abstract":"<div><div>Bone diseases profoundly affect patients, particularly the elderly, leading to severe health complications and disabilities. Osteoblasts play a crucial role in bone formation and are ideal candidates for treating bone diseases and engineering living materials. However, the stem and progenitor cells that give rise to osteoblasts, as well as osteoblasts themselves, exhibit dysfunction with aging. Although chemical reprogramming of fibroblasts into osteoblasts has been achieved, effective cell-based therapies or living materials have not been established in clinical practice. Here, we present a method to engineer fibroblasts through small molecule reprogramming and spheronization, achieving functional osteoblastic materials across all age groups. By primarily targeting the WNT signaling pathway and modularizing small molecules based on their effects on stage-specific genes, we optimized the temporal regulation of small molecules during reprogramming, acquiring a large number of healthy induced osteoblasts (iOBs). These iOBs with traits of functional native osteoblasts are ideal for forming transplantable tissue spheroids. As innovative living materials, the iOB spheroids (iOB-Sps) have demonstrated improved survival, significant self-bone formation, reduced ROS levels in the defect microenvironment, and accelerated endogenous osteogenesis and angiogenesis in vivo, promoting effective healing of bone defects. These material-free iOB-Sps function as self-scaffolding building blocks for biofunctional constructs, offering a promising avenue for clinical autologous bone defect repair, especially for the elderly.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"50 ","pages":"Pages 414-431"},"PeriodicalIF":18.0,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143863484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bioactive MaterialsPub Date : 2025-04-22DOI: 10.1016/j.bioactmat.2025.04.011
Maoyu Cai , Haiping Zhong , Xindi Wang , Liangpin Li , Xueyan Zhou , Yan Wang , Xia Hua , Shutao Guo , Xiaoyong Yuan
{"title":"Pathology-inspired collagen-binding thermosensitive micelle drops enable prolonged and efficient treatment of fungal keratitis","authors":"Maoyu Cai , Haiping Zhong , Xindi Wang , Liangpin Li , Xueyan Zhou , Yan Wang , Xia Hua , Shutao Guo , Xiaoyong Yuan","doi":"10.1016/j.bioactmat.2025.04.011","DOIUrl":"10.1016/j.bioactmat.2025.04.011","url":null,"abstract":"<div><div>Fungal keratitis (FK) is a challenging-to-manage blinding corneal infectious disease that often leads to severe sequelae, such as corneal leukoplakia regardless of curative care. Moreover, the unique anatomical structure and tear turnover of the eye significantly limit the bioavailability and therapeutic efficacy of traditional eye drops. Inspired by the unique pathological features of corneal ulcers, we report a thermosensitive multifunctional eye drop, designated PX-TA, based on a poloxamer (PX) and a collagen-adhesive tannic acid (TA), for prolonged and efficient treatment of FK. PX-TA transforms into a gel at body temperature and adheres to exposed collagen at the ulcer site; this significantly improves the corneal retention time and bioavailability. PX-TA maintains corneal retention for at least 90 min, substantially exceeding both the 15-min limit of commercial mucoadhesive eye drops and the 30-min threshold of conventional in situ gels. When loaded with amphotericin B (AmB), once-daily PX-TA-AmB administration effectively suppresses inflammation and corneal scarring, demonstrating superior efficacy over six-times-daily free AmB drops and a good safety profile. Mechanistic investigations reveal that PX-TA-AmB mediates its therapeutic effects through the MAPK6/PI3K/AKT signaling pathway. Moreover, the metal-chelating properties of TA inhibit the copper-dependent enzyme lysyl oxidase (LOX), resulting in reduced matrix fibrosis. Overall, the use of PX-TA-AmB drops represents a simplified yet effective strategy for the potential clinical management of FK, inspiring the design of eye drop formulations.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"50 ","pages":"Pages 396-413"},"PeriodicalIF":18.0,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143859976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bioactive MaterialsPub Date : 2025-04-22DOI: 10.1016/j.bioactmat.2025.04.013
Zhen Zhang , Ye Huang , Xu Hu , Yulei Mu , Huiqun Zhou , Liang Ma , Bangheng Liu , Hang Yao , Xieyuan Jiang , Dong-An Wang
{"title":"In situ implantation of type II collagen-based double-layer scaffolds for Articular Osteochondral Regeneration comprising hyaline cartilage and vascularized subchondral bones","authors":"Zhen Zhang , Ye Huang , Xu Hu , Yulei Mu , Huiqun Zhou , Liang Ma , Bangheng Liu , Hang Yao , Xieyuan Jiang , Dong-An Wang","doi":"10.1016/j.bioactmat.2025.04.013","DOIUrl":"10.1016/j.bioactmat.2025.04.013","url":null,"abstract":"<div><div>The articular osteochondral injury involves the repair of hyaline cartilage, subchondral bone plate, and cancellous bone. Due to the weak regeneration ability of chondrocytes and the complex structure of the bone-cartilage junction, there is currently no excellent repair method. The challenge of hyaline cartilage repair is to avoid fibrosis and hypertrophy, which has been solved to some extent after the advent of type II collagen scaffolds; the difficulty of the subchondral bone plate and cancellous bone repair lies in the repair of the complex transition structure of cartilage tidemark, calcified cartilage, subchondral bone plate, and cancellous bone. Inspired by developmental biology, the generation of this complex structure during development depends on endochondral ossification (ECO). ECO depends on some specific proteins, such as IHH, PTHrP, BMP, and WNT, and the receptors of these proteins. Studies have shown that polydopamine coating can promote the production of BMP and WNT proteins. We developed a type II collagen-based double-layer scaffold (Col II & Dopa-Col II) with type II collagen on the upper layer and polydopamine-coated type II collagen on the lower layer. Proteomics and RNA sequencing analysis have found that polydopamine coating can mobilize the proliferation and hypertrophy differentiation of chondrocytes, induce intra-chondral vascular nerve invasion, and promote ECO and bone remodeling by upregulating Parathyroid hormone signaling pathway, Hedgehog signaling pathway, VEGF signaling pathway, and Axon guidance. All the results indicate that Col II & Dopa-Col II can achieve hyaline cartilage and vascularized subchondral bone regeneration.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"50 ","pages":"Pages 364-381"},"PeriodicalIF":18.0,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143856030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bioactive MaterialsPub Date : 2025-04-22DOI: 10.1016/j.bioactmat.2025.04.022
Bicong Gao , Haifeng Ni , Junhong Lai , Ning Gao , Xinxin Luo , Ying Wang , Yani Chen , Jiaying Zhao , Zhou Yu , Jing Zhang , Wenjin Cai , Guoli Yang
{"title":"Macrophage response to fibrin structure mediated by Tgm2-dependent mitochondrial mechanosensing","authors":"Bicong Gao , Haifeng Ni , Junhong Lai , Ning Gao , Xinxin Luo , Ying Wang , Yani Chen , Jiaying Zhao , Zhou Yu , Jing Zhang , Wenjin Cai , Guoli Yang","doi":"10.1016/j.bioactmat.2025.04.022","DOIUrl":"10.1016/j.bioactmat.2025.04.022","url":null,"abstract":"<div><div>Following an injury at the implantation position, blood-material interactions form a fibrin architecture, which serves as the initial activator of foreign body response (FBR). However, there is limited knowledge regarding how the topography of fibrin architectures regulates macrophage behavior in mitigating FBR. Mechanical cues of the microenvironment have been reported to shape immune cell functions. Here, we investigated macrophage mechanobiology at the organelle level by constructing heterogeneous fibrin networks. Based on findings <em>in vivo</em>, we demonstrated that adhesion-mediated differentiation of mitochondrial function modulated macrophage polarization. The finite activation of integrin signaling upregulated transglutaminase 2 (Tgm2) in a trans-manner, augments PGC1α-mediated mitochondrial biogenesis. Our study highlighted the previously overlooked spatial structures of host proteins adsorbed on material surfaces, advocating for a paradigm shift in material design strategies, from focusing solely on physical properties to considering the modification of host proteins.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"50 ","pages":"Pages 382-395"},"PeriodicalIF":18.0,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143856007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bioactive MaterialsPub Date : 2025-04-18DOI: 10.1016/j.bioactmat.2025.04.009
Yu-Bao Liu , Xu Liu , Xiao-Fei Li , Liang Qiao , Hao-Liang Wang , Yue-Fu Dong , Feng Zhang , Yang Liu , Hao-Yang Liu , Ming-Liang Ji , Lan Li , Qing Jiang , Jun Lu
{"title":"Multifunctional piezoelectric hydrogels under ultrasound stimulation boost chondrogenesis by recruiting autologous stem cells and activating the Ca2+/CaM/CaN signaling pathway","authors":"Yu-Bao Liu , Xu Liu , Xiao-Fei Li , Liang Qiao , Hao-Liang Wang , Yue-Fu Dong , Feng Zhang , Yang Liu , Hao-Yang Liu , Ming-Liang Ji , Lan Li , Qing Jiang , Jun Lu","doi":"10.1016/j.bioactmat.2025.04.009","DOIUrl":"10.1016/j.bioactmat.2025.04.009","url":null,"abstract":"<div><div>Articular cartilage, owing to the lack of undifferentiated stem cells after injury, faces significant challenges in reconstruction and repair, making it a major clinical challenge. Therefore, there is an urgent need to design a multifunctional hydrogels capable of recruiting autologous stem cells to achieve <em>in situ</em> cartilage regeneration. Here, our study investigated the potential of a piezoelectric hydrogel (Hyd<sub>6</sub>) for enhancing cartilage regeneration through ultrasound (US) stimulation. Hyd<sub>6</sub> has multiple properties including injectability, self-healing capabilities, and piezoelectric characteristics. These properties synergistically promote stem cell chondrogenesis. The fabrication and characterization of Hyd<sub>6</sub> revealed its excellent biocompatibility, biodegradability, and electromechanical conversion capabilities. <em>In vitro</em> and <em>in vivo</em> experiments revealed that Hyd<sub>6</sub>, when combined with US stimulation, significantly promotes the recruitment of autologous stem cells and enhances chondrogenesis by generating electrical signals that promote the influx of Ca<sup>2+</sup>, activating downstream CaM/CaN signaling pathways and accelerating cartilage formation. An <em>in vivo</em> study in a rabbit model of chondral defects revealed that Hyd<sub>6</sub> combined with US treatment significantly improved cartilage regeneration, as evidenced by better integration of the regenerated tissue with the surrounding cartilage, greater collagen type II expression, and improved mechanical properties. The results highlight the potential of Hyd<sub>6</sub> as a novel therapeutic approach for treating cartilage injuries, offering a self-powered, noninvasive, and effective strategy for tissue engineering and regenerative medicine.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"50 ","pages":"Pages 344-363"},"PeriodicalIF":18.0,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143844525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bioactive MaterialsPub Date : 2025-04-16DOI: 10.1016/j.bioactmat.2025.04.012
Li Yu , Hui Shi , Tingxin Gao , Wenrong Xu , Hui Qian , Jiajia Jiang , Xiao Yang , Xingdong Zhang
{"title":"Exomeres and supermeres: Current advances and perspectives","authors":"Li Yu , Hui Shi , Tingxin Gao , Wenrong Xu , Hui Qian , Jiajia Jiang , Xiao Yang , Xingdong Zhang","doi":"10.1016/j.bioactmat.2025.04.012","DOIUrl":"10.1016/j.bioactmat.2025.04.012","url":null,"abstract":"<div><div>Recent studies have revealed a great diversity and complexity in extracellular vesicles and particles (EVPs). The developments in techniques and the growing awareness of the particle heterogeneity have spurred active research on new particle subsets. Latest discoveries highlighted unique features and roles of non-vesicular extracellular nanoparticles (NVEPs) as promising biomarkers and targets for diseases. These nanoparticles are distinct from extracellular vesicles (EVs) in terms of their smaller particle sizes and lack of a bilayer membrane structure and they are enriched with diverse bioactive molecules particularly proteins and RNAs, which are widely reported to be delivered and packaged in exosomes. This review is focused on the two recently identified membraneless NVEPs, exomeres and supermeres, to provide an overview of their biogenesis and contents, particularly those bioactive substances linked to their bio-properties. This review also explains the concepts and characteristics of these nanoparticles, to compare them with other EVPs, especially EVs, as well as to discuss their isolation and identification methods, research interests, potential clinical applications and open questions.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"50 ","pages":"Pages 322-343"},"PeriodicalIF":18.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143834501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bioactive MaterialsPub Date : 2025-04-16DOI: 10.1016/j.bioactmat.2025.03.021
Mariagiulia Spazzapan , Silvia Pegoraro , Roman Vuerich , Gabriella Zito , Andrea Balduit , Elena Longo , Lorella Pascolo , Miriam Toffoli , Giorgia Meshini , Alessandro Mangogna , Gloria Ros , Francesca Buonomo , Federico Romano , Letizia Lombardelli , Giovanni Papa , Marie-Pierre Piccinni , Serena Zacchigna , Chiara Agostinis , Roberta Bulla , Giuseppe Ricci
{"title":"Endothelial cell supplementation promotes xenograft revascularization during short-term ovarian tissue transplantation","authors":"Mariagiulia Spazzapan , Silvia Pegoraro , Roman Vuerich , Gabriella Zito , Andrea Balduit , Elena Longo , Lorella Pascolo , Miriam Toffoli , Giorgia Meshini , Alessandro Mangogna , Gloria Ros , Francesca Buonomo , Federico Romano , Letizia Lombardelli , Giovanni Papa , Marie-Pierre Piccinni , Serena Zacchigna , Chiara Agostinis , Roberta Bulla , Giuseppe Ricci","doi":"10.1016/j.bioactmat.2025.03.021","DOIUrl":"10.1016/j.bioactmat.2025.03.021","url":null,"abstract":"<div><div>The ischemic/hypoxic window after Ovarian Tissue Transplantation (OTT) can be responsible for the loss of more than 60 % of follicles. The implantation of the tissue supplemented with endothelial cells (ECs) inside dermal substitutes represents a promising strategy for improving graft revascularization. Ovarian biopsies were partly cryopreserved and partly digested to isolate ovarian ECs (OVECs). Four dermal substitutes (Integra®, made of bovine collagen enriched with chondroitin 6-sulfate; PELNAC®, composed of porcine collagen; Myriad Matrix®, derived from decellularized ovine forestomach; and NovoSorb® BMT, a foam of polyurethane) were compared for their angiogenic bioactive properties.</div><div>OVECs cultured onto the scaffolds upregulated the expression of angiogenic factors, supporting their use in boosting revascularization. Adhesion and proliferation assays suggested that the most suitable scaffold was the bovine collagen one, which was chosen for further <em>in vivo</em> experiments. Cryopreserved tissue was transplanted onto the 3D scaffold in immunodeficient mice with or without cell supplementation, and after 14 days, it was analyzed by immunofluorescence (IF) and X-ray phase contrast microtomography. The revascularization area of OVECs-supplemented tissue was doubled (7.14 %) compared to the scaffold transplanted alone (3.67 %). Furthermore, tissue viability, evaluated by nuclear counting, was significantly higher (mean of 169.6 nuclei/field) in the tissue grafted with OVECs than in the tissue grafted alone (mean of 87.2 nuclei/field).</div><div>Overall, our findings suggest that the OVECs-supplementation shortens the ischemic interval and may significantly improve fertility preservation procedures.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"50 ","pages":"Pages 305-321"},"PeriodicalIF":18.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143834500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A biodegradable, microstructured, electroconductive and nano-integrated drug eluting patch (MENDEP) for myocardial tissue engineering","authors":"Caterina Cristallini , Daniela Rossin , Roberto Vanni , Niccoletta Barbani , Chiara Bulgheresi , Massimiliano Labardi , Sadia Perveen , Silvia Burchielli , Domiziana Terlizzi , Claudia Kusmic , Silvia Del Ry , Manuela Cabiati , Cheherazade Trouki , Dawid Rossino , Francesca Sergi , Anthea Villano , Giovanni D. Aquaro , Giorgia Scarpellino , Federico A. Ruffinatti , Sara Amorim , Claudia Giachino","doi":"10.1016/j.bioactmat.2025.04.008","DOIUrl":"10.1016/j.bioactmat.2025.04.008","url":null,"abstract":"<div><div>We produced a microstructured, electroconductive and nano-functionalized drug eluting cardiac patch (MENDEP) designed to attract endogenous precursor cells, favor their differentiation and counteract adverse ventricular remodeling <em>in situ</em>. MENDEP showed mechanical anisotropy and biaxial strength comparable to porcine myocardium, reduced impedance, controlled biodegradability, molecular recognition ability and controlled drug release activity. <em>In vitro</em>, cytocompatibility and cardioinductivity were demonstrated. Migration tests showed the chemoattractive capacity of the patches and conductivity assays showed unaltered cell-cell interactions and cell beating synchronicity. MENDEP was then epicardially implanted in a rat model of ischemia/reperfusion (I/R). Histological, immunofluorescence and biomarker analysis indicated that implantation did not cause damage to the healthy myocardium. After I/R, MENDEP recruited precursor cells into the damaged myocardium and triggered their differentiation towards the vascular lineage. Under the patch, the myocardial tissue appeared well preserved and cardiac gap junctions were correctly distributed at the level of the intercalated discs. The fibrotic area measured in the I/R group was partially reduced in the patch group.</div><div>Overall, these results demonstrate that MENDEP was fully retained on the epicardial surface of the left ventricle over 4-week implantation period, underwent progressive vascularization, did not perturb the healthy myocardium and showed great potential in repairing the infarcted area.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"50 ","pages":"Pages 246-272"},"PeriodicalIF":18.0,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143825449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bioactive MaterialsPub Date : 2025-04-14DOI: 10.1016/j.bioactmat.2025.04.007
Xin Zhang , Shufang Wang , Siyu Wang , Zeyi Long , Cong Lu , Jianlin Wang , Lijun Yang , Cancan Yao , Bin He , Xihua Chen , Taifeng Zhuang , Xiangbo Xu , Yufeng Zheng
{"title":"A double network composite hydrogel with enhanced transdermal delivery by ultrasound for endometrial injury repair and fertility recovery","authors":"Xin Zhang , Shufang Wang , Siyu Wang , Zeyi Long , Cong Lu , Jianlin Wang , Lijun Yang , Cancan Yao , Bin He , Xihua Chen , Taifeng Zhuang , Xiangbo Xu , Yufeng Zheng","doi":"10.1016/j.bioactmat.2025.04.007","DOIUrl":"10.1016/j.bioactmat.2025.04.007","url":null,"abstract":"<div><div>Endometrial injury and resulting female infertility pose significant clinical challenges due to the notable shortcomings of traditional treatments. Herein, we proposed a double network composite hydrogel, CSMA-RC-Zn-PNS, which forms a physical barrier on damaged tissue through photo-crosslinking while enabling sustained release of the active ingredient PNS. Based on this, we developed a combined strategy to enhance transdermal delivery efficiency using ultrasound cavitation. <em>In vitro</em> experiments demonstrated that CSMA-RC-Zn-PNS exhibits excellent biosafety, biodegradability, and promotes cell proliferation, migration, and tube formation, along with antioxidant and antibacterial properties. In a rat endometrial injury model, the ultrasound cavitation effect was demonstrated to enhance transdermal delivery efficiency, and the ability of CSMA-RC-Zn-PNS to promote endometrial regeneration, anti-fibrosis and fertility restoration was verified. Overall, this strategy combining CSMA-RC-Zn-PNS hydrogel and ultrasound treatment shows promising applications in endometrial regeneration and female reproductive health.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"50 ","pages":"Pages 273-286"},"PeriodicalIF":18.0,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143825450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bioactive MaterialsPub Date : 2025-04-14DOI: 10.1016/j.bioactmat.2025.04.002
Shuo Liu , Lu Song , Shuwen Huang , Zhanhong Liu , Yang Xu , Zhiyuan Wang , He Qiu , Jing Wang , Zhiru Chen , Yumei Xiao , Hang Wang , Xiangdong Zhu , Kai Zhang , Xingdong Zhang , Hai Lin
{"title":"Hydroxyapatite microspheres encapsulated within hybrid hydrogel promote skin regeneration through the activation of Calcium Signaling and Motor Protein pathway","authors":"Shuo Liu , Lu Song , Shuwen Huang , Zhanhong Liu , Yang Xu , Zhiyuan Wang , He Qiu , Jing Wang , Zhiru Chen , Yumei Xiao , Hang Wang , Xiangdong Zhu , Kai Zhang , Xingdong Zhang , Hai Lin","doi":"10.1016/j.bioactmat.2025.04.002","DOIUrl":"10.1016/j.bioactmat.2025.04.002","url":null,"abstract":"<div><div>Hydroxyapatite (HAp), traditionally recognized for its efficacy in bone regeneration, has rarely been explored for skin regeneration applications. This investigation explored HAp microspheres with distinct physicochemical properties tailored away from conventional bone regeneration parameters, and the capacity promoting skin regeneration and mitigating the aging process were investigated when encapsulated in hyaluronate hydrogels. By benchmarking against well-established dermal fillers like PMMA and PLLA, it was revealed the specific attributes of HAp that were conducive to skin regeneration, providing initial insights into the underlying mechanism. HAp enhanced the fibroblast functionality by triggering minimal adaptive immune responses and enhancing the Calcium Signaling and Motor Protein Signaling pathways. This modulation supported the production of normal collagen fibers, essential for ECM maturation and skin structural integrity. The significant ECM regeneration and remodeling capabilities exhibited by the HAp-encapsulated hybrid hydrogels suggested promising application in facial rejuvenation procedures, potentially making a breakthrough in aesthetic and reconstructive surgery.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"50 ","pages":"Pages 287-304"},"PeriodicalIF":18.0,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143829246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}