Pub Date : 2024-12-01DOI: 10.1016/j.bioactmat.2024.11.017
Jian Wang , Dongyang Zhou , Ruiyang Li , Shihao Sheng , Guangfeng Li , Yue Sun , Peng Wang , Yulin Mo , Han Liu , Xiao Chen , Zhen Geng , Qin Zhang , Yingying Jing , Long Bai , Ke Xu , Jiacan Su
Bone organoids are emerging as powerful tools for studying bone development and related diseases. However, the simplified design of current methods somewhat limits their application potential, as these methods produce single-tissue organoids that fail to replicate the bone microarchitecture or achieve effective mineralization. To address this issue, we propose a three-dimensional (3D) construction strategy for generating mineralized bone structures using bone marrow-derived mesenchymal stem cells (BMSCs). By mixing BMSCs with hydrogel to create a bone matrix-mimicking bioink and employing projection-based light-curing 3D printing technology, we constructed 3D-printed structures, which were then implanted subcutaneously into nude mice, away from the native bone microenvironment. Even without external stimulation, these implants spontaneously formed mineralized bone domains. With long-term culture, these structures gradually matured into fully differentiated bone tissue, completing both mineralization and vascularization. This in vivo bone organoid model offers a novel platform for studying bone development, exploring congenital diseases, testing drugs, and developing therapeutic applications.
{"title":"Protocol for engineering bone organoids from mesenchymal stem cells","authors":"Jian Wang , Dongyang Zhou , Ruiyang Li , Shihao Sheng , Guangfeng Li , Yue Sun , Peng Wang , Yulin Mo , Han Liu , Xiao Chen , Zhen Geng , Qin Zhang , Yingying Jing , Long Bai , Ke Xu , Jiacan Su","doi":"10.1016/j.bioactmat.2024.11.017","DOIUrl":"10.1016/j.bioactmat.2024.11.017","url":null,"abstract":"<div><div>Bone organoids are emerging as powerful tools for studying bone development and related diseases. However, the simplified design of current methods somewhat limits their application potential, as these methods produce single-tissue organoids that fail to replicate the bone microarchitecture or achieve effective mineralization. To address this issue, we propose a three-dimensional (3D) construction strategy for generating mineralized bone structures using bone marrow-derived mesenchymal stem cells (BMSCs). By mixing BMSCs with hydrogel to create a bone matrix-mimicking bioink and employing projection-based light-curing 3D printing technology, we constructed 3D-printed structures, which were then implanted subcutaneously into nude mice, away from the native bone microenvironment. Even without external stimulation, these implants spontaneously formed mineralized bone domains. With long-term culture, these structures gradually matured into fully differentiated bone tissue, completing both mineralization and vascularization. This <em>in vivo</em> bone organoid model offers a novel platform for studying bone development, exploring congenital diseases, testing drugs, and developing therapeutic applications.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"45 ","pages":"Pages 388-400"},"PeriodicalIF":18.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142757627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-30DOI: 10.1016/j.bioactmat.2024.11.020
Jua Kim , Jeremy L. Gilbert , William W. Lv , Ping Du , Haobo Pan
Magnesium (Mg) alloys are popular biodegradable metals studied for orthopedic and cardiovascular applications, mainly because Mg ions are essential trace elements known to promote angiogenesis and osteogenesis. However, Mg corrosion consists of oxidation and reduction reactions that produce by-products, such as hydrogen gas, reactive oxygen species, and hydroxides. It is still unclear how all these by-products and Mg ions concomitantly alter the microenvironment and cell behaviors spatially and temporally. This study shows that Mg corrosion can enhance cell proliferation by reducing intracellular ROS. However, Mg cannot decrease ROS and promote cell proliferation in simulated inflammatory conditions, meaning the microenvironment is critical. Furthermore, cells may respond to Mg ions differently in chronic or acute alkaline pH or oxidative stress. Depending on the corrosion rate, Mg modulates HIF1α and many signaling pathways like PI3K/AKT/mTOR, mitophagy, cell cycle, and oxidative phosphorylation. Therefore, this study provides a fundamental insight into the importance of reduction reactions in Mg alloys.
{"title":"Reduction reactions dominate the interactions between Mg alloys and cells: Understanding the mechanisms","authors":"Jua Kim , Jeremy L. Gilbert , William W. Lv , Ping Du , Haobo Pan","doi":"10.1016/j.bioactmat.2024.11.020","DOIUrl":"10.1016/j.bioactmat.2024.11.020","url":null,"abstract":"<div><div>Magnesium (Mg) alloys are popular biodegradable metals studied for orthopedic and cardiovascular applications, mainly because Mg ions are essential trace elements known to promote angiogenesis and osteogenesis. However, Mg corrosion consists of oxidation and reduction reactions that produce by-products, such as hydrogen gas, reactive oxygen species, and hydroxides. It is still unclear how all these by-products and Mg ions concomitantly alter the microenvironment and cell behaviors spatially and temporally. This study shows that Mg corrosion can enhance cell proliferation by reducing intracellular ROS. However, Mg cannot decrease ROS and promote cell proliferation in simulated inflammatory conditions, meaning the microenvironment is critical. Furthermore, cells may respond to Mg ions differently in chronic or acute alkaline pH or oxidative stress. Depending on the corrosion rate, Mg modulates HIF1α and many signaling pathways like PI3K/AKT/mTOR, mitophagy, cell cycle, and oxidative phosphorylation. Therefore, this study provides a fundamental insight into the importance of reduction reactions in Mg alloys.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"45 ","pages":"Pages 363-387"},"PeriodicalIF":18.0,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142757628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-27DOI: 10.1016/j.bioactmat.2024.11.026
Sayan Deb Dutta , Jeong Man An , Jin Hexiu , Aayushi Randhawa , Keya Ganguly , Tejal V. Patil , Thavasyappan Thambi , Jangho Kim , Yong-kyu Lee , Ki-Taek Lim
Biomaterial composition and surface charge play a critical role in macrophage polarization, providing a molecular cue for immunomodulation and tissue regeneration. In this study, we developed bifunctional hydrogel inks for accelerating M2 macrophage polarization and exosome (Exo) cultivation for wound healing applications. For this, we first fabricated polyamine-modified three-dimensional (3D) printable hydrogels consisting of alginate/gelatin/polydopamine nanospheres (AG/NSPs) to boost M2-exosome (M2-Exo) secretion. The cultivated M2-Exo were finally encapsulated into a biocompatible collagen/decellularized extracellular matrix (COL@d-ECM) bioink for studying angiogenesis and in vivo wound healing study. Our findings show that 3D-printed AGP hydrogel promoted M2 macrophage polarization by Janus kinase/signal transducer of activation (JAK/STAT), peroxisome proliferator-activated receptor (PPAR) signaling pathways and facilitated the M2-Exo secretion. Moreover, the COL@d-ECM/M2-Exo was found to be biocompatible with skin cells. Transcriptomic (RNA-Seq) and real-time PCR (qRT-PCR) study revealed that co-culture of fibroblast/keratinocyte/stem cells/endothelial cells in a 3D bioprinted COL@d-ECM/M2-Exo hydrogel upregulated the skin-associated signature biomarkers through various regulatory pathways during epidermis remodeling and downregulated the mitogen-activated protein kinase (MAPK) signaling pathway after 7 days. In a subcutaneous wound model, the 3D bioprinted COL@d-ECM/M2-Exo hydrogel displayed robust wound remodeling and hair follicle (HF) induction while reducing canonical pro-inflammatory activation after 14 days, presenting a viable therapeutic strategy for skin-related disorders.
{"title":"3D bioprinting of engineered exosomes secreted from M2-polarized macrophages through immunomodulatory biomaterial promotes in vivo wound healing and angiogenesis","authors":"Sayan Deb Dutta , Jeong Man An , Jin Hexiu , Aayushi Randhawa , Keya Ganguly , Tejal V. Patil , Thavasyappan Thambi , Jangho Kim , Yong-kyu Lee , Ki-Taek Lim","doi":"10.1016/j.bioactmat.2024.11.026","DOIUrl":"10.1016/j.bioactmat.2024.11.026","url":null,"abstract":"<div><div>Biomaterial composition and surface charge play a critical role in macrophage polarization, providing a molecular cue for immunomodulation and tissue regeneration. In this study, we developed bifunctional hydrogel inks for accelerating M2 macrophage polarization and exosome (Exo) cultivation for wound healing applications. For this, we first fabricated polyamine-modified three-dimensional (3D) printable hydrogels consisting of alginate/gelatin/polydopamine nanospheres (AG/NSPs) to boost M2-exosome (M2-Exo) secretion. The cultivated M2-Exo were finally encapsulated into a biocompatible collagen/decellularized extracellular matrix (COL@d-ECM) bioink for studying angiogenesis and <em>in vivo</em> wound healing study. Our findings show that 3D-printed AGP hydrogel promoted M2 macrophage polarization by Janus kinase/signal transducer of activation (JAK/STAT), peroxisome proliferator-activated receptor (PPAR) signaling pathways and facilitated the M2-Exo secretion. Moreover, the COL@d-ECM/M2-Exo was found to be biocompatible with skin cells. Transcriptomic (RNA-Seq) and real-time PCR (qRT-PCR) study revealed that co-culture of fibroblast/keratinocyte/stem cells/endothelial cells in a 3D bioprinted COL@d-ECM/M2-Exo hydrogel upregulated the skin-associated signature biomarkers through various regulatory pathways during epidermis remodeling and downregulated the mitogen-activated protein kinase (MAPK) signaling pathway after 7 days. In a subcutaneous wound model, the 3D bioprinted COL@d-ECM/M2-Exo hydrogel displayed robust wound remodeling and hair follicle (HF) induction while reducing canonical pro-inflammatory activation after 14 days, presenting a viable therapeutic strategy for skin-related disorders.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"45 ","pages":"Pages 345-362"},"PeriodicalIF":18.0,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142722062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-27DOI: 10.1016/j.bioactmat.2024.11.028
Tao Zhang , Xin-Cao Zhong , Zi-Xuan Feng , Xiao-Ying Lin , Chun-Ye Chen , Xiao-Wei Wang , Kai Guo , Yi Wang , Jun Chen , Yong-Zhong Du , Ze-Ming Zhuang , Yong Wang , Wei-Qiang Tan
Achieving scar-free skin regeneration in clinical settings presents significant challenges. Key issues such as the imbalance in macrophage phenotype transition, delayed re-epithelialization, and excessive proliferation and differentiation of fibroblasts hinder wound healing and lead to fibrotic repair. To these, we developed an active shrinkage and antioxidative hydrogel with biomimetic mechanical functions (P&G@LMs) to reshape the healing microenvironment and effectively promote skin regeneration. The hydrogel's immediate hemostatic effect initiated sequential remodeling, the active shrinkage property sealed and contracted the wound at body temperature, and the antioxidative function eliminated ROS, promoting re-epithelialization. The spatiotemporal release of LMs (ACEI) during the inflammation phase regulated macrophage polarization towards the anti-inflammatory M2 phenotype, promoting progression to the proliferation phase. However, the profibrotic niche of macrophages induced a highly contractile α-SMA positive state in myofibroblasts, whereas the sustained LMs release could regulate this niche to control fibrosis and promote the correct biomechanical orientation of collagen. Notably, the biomimetic mechanics of the hydrogel mimicked the contraction characteristics of myofibroblasts, and the skin-like elastic modulus could accommodate the skin dynamic changes and restore the mechanical integrity of wound defect, partially substituting myofibroblasts' mechanical role in tissue repair. This study presents an innovative strategy for skin regeneration.
{"title":"An active shrinkage and antioxidative hydrogel with biomimetic mechanics functions modulates inflammation and fibrosis to promote skin regeneration","authors":"Tao Zhang , Xin-Cao Zhong , Zi-Xuan Feng , Xiao-Ying Lin , Chun-Ye Chen , Xiao-Wei Wang , Kai Guo , Yi Wang , Jun Chen , Yong-Zhong Du , Ze-Ming Zhuang , Yong Wang , Wei-Qiang Tan","doi":"10.1016/j.bioactmat.2024.11.028","DOIUrl":"10.1016/j.bioactmat.2024.11.028","url":null,"abstract":"<div><div>Achieving scar-free skin regeneration in clinical settings presents significant challenges. Key issues such as the imbalance in macrophage phenotype transition, delayed re-epithelialization, and excessive proliferation and differentiation of fibroblasts hinder wound healing and lead to fibrotic repair. To these, we developed an active shrinkage and antioxidative hydrogel with biomimetic mechanical functions (P&G@LMs) to reshape the healing microenvironment and effectively promote skin regeneration. The hydrogel's immediate hemostatic effect initiated sequential remodeling, the active shrinkage property sealed and contracted the wound at body temperature, and the antioxidative function eliminated ROS, promoting re-epithelialization. The spatiotemporal release of LMs (ACEI) during the inflammation phase regulated macrophage polarization towards the anti-inflammatory M2 phenotype, promoting progression to the proliferation phase. However, the profibrotic niche of macrophages induced a highly contractile α-SMA positive state in myofibroblasts, whereas the sustained LMs release could regulate this niche to control fibrosis and promote the correct biomechanical orientation of collagen. Notably, the biomimetic mechanics of the hydrogel mimicked the contraction characteristics of myofibroblasts, and the skin-like elastic modulus could accommodate the skin dynamic changes and restore the mechanical integrity of wound defect, partially substituting myofibroblasts' mechanical role in tissue repair. This study presents an innovative strategy for skin regeneration.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"45 ","pages":"Pages 322-344"},"PeriodicalIF":18.0,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142722067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-27DOI: 10.1016/j.bioactmat.2024.11.029
Xiaoliang Qi , Yajing Xiang , Ying Li , Jiajia Wang , Yuxi Chen , Yulong Lan , Jinsong Liu , Jianliang Shen
Adenosine triphosphate (ATP)-activated prodrug approaches demonstrate potential in antibacterial uses. However, their efficacy frequently faces obstacles due to uncontrolled premature activation and spatiotemporal distribution differences under physiological circumstances. Herein, we present an endogenous ATP-activated prodrug system (termed ISD3) consisting of nanoparticles (indole-3-acetic acid/zeolitic imidazolate framework-8@polydopamine@platinum, IZPP) embedded in a silk fibroin-based hydrogel, aimed at treating multidrug-resistant (MDR) bacteria-infected pressure ulcers. Initially, an ultraviolet-triggered adhesive ISD3 barrier is formed over the pressure ulcer wound by a simple local injection. Subsequently, the bacteria-secreted ATP prompts the degradation of IZPP, allowing the loaded IAA prodrug and nanozyme to encounter spatiotemporally on a single carrier, thereby efficiently generating reactive oxygen species (ROS). Exposure to 808 nm near-infrared light enhances the catalytic reaction speed, boosting ROS levels for stronger antibacterial action. Once optimal antibacterial action is reached, ISD3 switches to a dormant state, halting any further ROS production. Moreover, the bioactive components in ISD3 can exert anti-inflammatory functions, aiding in pressure ulcer recovery. Overall, our research introduces a hydrogel prodrug strategy activated by bacterial endogenous ATP, which precisely manages ROS generation and accelerates the recovery of MDR bacteria-infected pressure ulcers.
由三磷酸腺苷（ATP）激活的原药方法在抗菌方面具有潜力。然而，由于过早活化不受控制以及生理情况下的时空分布差异，它们的功效经常面临障碍。在此，我们介绍一种内源性 ATP 激活原药系统（称为 ISD3），该系统由纳米颗粒（吲哚-3-乙酸/唑基咪唑啉框架-8@多巴胺@铂，IZPP）组成，嵌入丝纤维素基水凝胶中，旨在治疗耐多药（MDR）细菌感染的压疮。首先，通过简单的局部注射，在压疮伤口上形成一个紫外线触发的粘附性 ISD3 屏障。随后，细菌分泌的 ATP 促使 IZPP 降解，使负载的 IAA 原药和纳米酶在单一载体上时空相遇，从而有效地产生活性氧（ROS）。在 808 纳米近红外线的照射下，催化反应的速度会加快，从而提高 ROS 水平，加强抗菌作用。一旦达到最佳抗菌效果，ISD3 就会转入休眠状态，停止进一步产生 ROS。此外，ISD3 中的生物活性成分还具有抗炎功能，有助于压疮的恢复。总之，我们的研究引入了一种由细菌内源性 ATP 激活的水凝胶原药策略，它能精确管理 ROS 的产生，加速 MDR 细菌感染的压疮的恢复。
{"title":"An ATP-activated spatiotemporally controlled hydrogel prodrug system for treating multidrug-resistant bacteria-infected pressure ulcers","authors":"Xiaoliang Qi , Yajing Xiang , Ying Li , Jiajia Wang , Yuxi Chen , Yulong Lan , Jinsong Liu , Jianliang Shen","doi":"10.1016/j.bioactmat.2024.11.029","DOIUrl":"10.1016/j.bioactmat.2024.11.029","url":null,"abstract":"<div><div>Adenosine triphosphate (ATP)-activated prodrug approaches demonstrate potential in antibacterial uses. However, their efficacy frequently faces obstacles due to uncontrolled premature activation and spatiotemporal distribution differences under physiological circumstances. Herein, we present an endogenous ATP-activated prodrug system (termed ISD3) consisting of nanoparticles (indole-3-acetic acid/zeolitic imidazolate framework-8@polydopamine@platinum, IZPP) embedded in a silk fibroin-based hydrogel, aimed at treating multidrug-resistant (MDR) bacteria-infected pressure ulcers. Initially, an ultraviolet-triggered adhesive ISD3 barrier is formed over the pressure ulcer wound by a simple local injection. Subsequently, the bacteria-secreted ATP prompts the degradation of IZPP, allowing the loaded IAA prodrug and nanozyme to encounter spatiotemporally on a single carrier, thereby efficiently generating reactive oxygen species (ROS). Exposure to 808 nm near-infrared light enhances the catalytic reaction speed, boosting ROS levels for stronger antibacterial action. Once optimal antibacterial action is reached, ISD3 switches to a dormant state, halting any further ROS production. Moreover, the bioactive components in ISD3 can exert anti-inflammatory functions, aiding in pressure ulcer recovery. Overall, our research introduces a hydrogel prodrug strategy activated by bacterial endogenous ATP, which precisely manages ROS generation and accelerates the recovery of MDR bacteria-infected pressure ulcers.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"45 ","pages":"Pages 301-321"},"PeriodicalIF":18.0,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142722068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-26DOI: 10.1016/j.bioactmat.2024.11.027
Tingting Peng , Yangyan Chen , Xuanyu Luan , Wanshan Hu , Wentao Wu , Bing Guo , Chao Lu , Chuanbin Wu , Xin Pan
Skin infections caused by microbes such as bacteria, fungi, and viruses often lead to aberrant skin functions and appearance, eventually evolving into a significant risk to human health. Among different drug administration paradigms for skin infections, microneedles (MNs) have demonstrated superiority mainly because of their merits in enhancing drug delivery efficiency and reducing microbial resistance. Also, integrating biosensing functionality to MNs offers point-of-care wearable medical devices for analyzing specific pathogens, disease status, and drug pharmacokinetics, thus providing personalized therapy for skin infections. Herein, we do a timely update on the development of MN technology in skin infection management, with a special focus on how to devise MNs for personalized antimicrobial therapy. Notably, the advantages of state-of-the-art MNs for treating skin infections are pointed out, which include hijacking sequential drug transport barriers to enhance drug delivery efficiency and delivering various therapeutics (e.g., antibiotics, antimicrobial peptides, photosensitizers, metals, sonosensitizers, nanoenzyme, living bacteria, poly ionic liquid, and nanomoter). In addition, the nanoenzyme-based multimodal antimicrobial therapy is highlighted in addressing intractable infectious wounds. Furthermore, the MN-based biosensors used to identify pathogen types, track disease status, and quantify antibiotic concentrations are summarized. The limitations of antimicrobial MNs toward clinical translation are offered regarding large-scale production, quality control, and policy guidance. Finally, the future development of biosensing MNs with easy-to-use and intelligent properties and MN-based wearable drug delivery for home-based therapy are prospected. We hope this review will provide valuable guidance for future development in MN-mediated topical treatment of skin infections.
{"title":"Microneedle technology for enhanced topical treatment of skin infections","authors":"Tingting Peng , Yangyan Chen , Xuanyu Luan , Wanshan Hu , Wentao Wu , Bing Guo , Chao Lu , Chuanbin Wu , Xin Pan","doi":"10.1016/j.bioactmat.2024.11.027","DOIUrl":"10.1016/j.bioactmat.2024.11.027","url":null,"abstract":"<div><div>Skin infections caused by microbes such as bacteria, fungi, and viruses often lead to aberrant skin functions and appearance, eventually evolving into a significant risk to human health. Among different drug administration paradigms for skin infections, microneedles (MNs) have demonstrated superiority mainly because of their merits in enhancing drug delivery efficiency and reducing microbial resistance. Also, integrating biosensing functionality to MNs offers point-of-care wearable medical devices for analyzing specific pathogens, disease status, and drug pharmacokinetics, thus providing personalized therapy for skin infections. Herein, we do a timely update on the development of MN technology in skin infection management, with a special focus on how to devise MNs for personalized antimicrobial therapy. Notably, the advantages of state-of-the-art MNs for treating skin infections are pointed out, which include hijacking sequential drug transport barriers to enhance drug delivery efficiency and delivering various therapeutics (<em>e.g.</em>, antibiotics, antimicrobial peptides, photosensitizers, metals, sonosensitizers, nanoenzyme, living bacteria, poly ionic liquid, and nanomoter). In addition, the nanoenzyme-based multimodal antimicrobial therapy is highlighted in addressing intractable infectious wounds. Furthermore, the MN-based biosensors used to identify pathogen types, track disease status, and quantify antibiotic concentrations are summarized. The limitations of antimicrobial MNs toward clinical translation are offered regarding large-scale production, quality control, and policy guidance. Finally, the future development of biosensing MNs with easy-to-use and intelligent properties and MN-based wearable drug delivery for home-based therapy are prospected. We hope this review will provide valuable guidance for future development in MN-mediated topical treatment of skin infections.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"45 ","pages":"Pages 274-300"},"PeriodicalIF":18.0,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142699199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-26DOI: 10.1016/j.bioactmat.2024.11.025
Emma Steijvers , Yunshong Shi , Hong Lu , Weixin Zhang , Yitian Zhang , Feihu Zhao , Baichuan Wang , Louise Hughes , Jake E. Barralet , Giulia Degli-Alessandrini , Igor Kraev , Richard Johnston , Zengwu Shao , Frank H. Ebetino , James T. Triffitt , R. Graham G. Russell , Davide Deganello , Xu Cao , Zhidao Xia
Biomaterials are widely used as orthopaedic implants and bone graft substitutes. We aimed to develop a rapid osteogenic assessment method using a murine tibial periosteal ossification model to evaluate the bone formation/remodelling potential of a biomaterial within 2–4 weeks. A novel hydroxyapatite/aragonite (HAA) biomaterial was implanted into C57BL/6 mice juxtaskeletally between the tibia and tibialis anterior muscle. Rapid intramembranous bone formation was observed at 14 days, with 4- to 8-fold increases in bone thickness and callus volume in comparison with sham-operated animals (p < 0.0001), followed by bone remodelling and a new layer of cortical bone formation by 28 days after implantation. The addition of zoledronate, a clinically-utilised bisphosphonate, to HAA, promoted significantly more new bone formation than HAA alone over 28 days (p < 0.01). The osteogenic potential of HAA was further confirmed by implanting into a 3.5 mm diameter femoral cancellous bone defect in rats and a 5 mm diameter femoral cortical bone defect in minipigs. To understand the biodegradation and the cellular activity at the cell/biomaterial interfaces, non-decalcified specimens were resin embedded and sections subjected to combined scanning electron microscopy (SEM)/electron backscatter diffraction (EBSD)/energy dispersive X-ray spectrometry (EDS) analysis. We conclude that murine tibial periosteal ossification is a novel method for rapid assessment of the interaction of bioactive materials with osteogenic tissues. This study also highlights that combining calcium carbonate with hydroxyapatite enhances biodegradation and osteogenesis.
{"title":"Rapid assessment of the osteogenic capacity of hydroxyapatite/aragonite using a murine tibial periosteal ossification model","authors":"Emma Steijvers , Yunshong Shi , Hong Lu , Weixin Zhang , Yitian Zhang , Feihu Zhao , Baichuan Wang , Louise Hughes , Jake E. Barralet , Giulia Degli-Alessandrini , Igor Kraev , Richard Johnston , Zengwu Shao , Frank H. Ebetino , James T. Triffitt , R. Graham G. Russell , Davide Deganello , Xu Cao , Zhidao Xia","doi":"10.1016/j.bioactmat.2024.11.025","DOIUrl":"10.1016/j.bioactmat.2024.11.025","url":null,"abstract":"<div><div>Biomaterials are widely used as orthopaedic implants and bone graft substitutes. We aimed to develop a rapid osteogenic assessment method using a murine tibial periosteal ossification model to evaluate the bone formation/remodelling potential of a biomaterial within 2–4 weeks. A novel hydroxyapatite/aragonite (HAA) biomaterial was implanted into C57BL/6 mice juxtaskeletally between the tibia and tibialis anterior muscle. Rapid intramembranous bone formation was observed at 14 days, with 4- to 8-fold increases in bone thickness and callus volume in comparison with sham-operated animals (<em>p</em> < 0.0001), followed by bone remodelling and a new layer of cortical bone formation by 28 days after implantation. The addition of zoledronate, a clinically-utilised bisphosphonate, to HAA, promoted significantly more new bone formation than HAA alone over 28 days (<em>p</em> < 0.01). The osteogenic potential of HAA was further confirmed by implanting into a 3.5 mm diameter femoral cancellous bone defect in rats and a 5 mm diameter femoral cortical bone defect in minipigs. To understand the biodegradation and the cellular activity at the cell/biomaterial interfaces, non-decalcified specimens were resin embedded and sections subjected to combined scanning electron microscopy (SEM)/electron backscatter diffraction (EBSD)/energy dispersive X-ray spectrometry (EDS) analysis. We conclude that murine tibial periosteal ossification is a novel method for rapid assessment of the interaction of bioactive materials with osteogenic tissues. This study also highlights that combining calcium carbonate with hydroxyapatite enhances biodegradation and osteogenesis.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"45 ","pages":"Pages 257-273"},"PeriodicalIF":18.0,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142699198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-25DOI: 10.1016/j.bioactmat.2024.11.022
Yi Qian , Yan Chen , Jimiao Jiang , Jia Pei , Junfei Li , Jialin Niu , Jinzhou Zhu , Guangyin Yuan
In this study, biodegradable Zn-Cu-Mn alloy stents were implanted into porcine coronary artery for 18 months, and the in vivo biosafety and efficacy as well as the degradation behavior were systematically studied. Results showed a rapid endothelialization of the target vessel was achieved at 1 month post-implantation. Although the lumen diameter loss and local inflammation were observed at the early stage, the stented blood vessel could gradually recover with time. The lumen diameter was already close to normal range at 12 months, indicating good bioefficacy of the stent. No adverse effect on blood indexes or local accumulation of Zn, Cu or Mn elements were found after implantation, neither the malapposition and thrombosis were observed, which exhibited good biosafety of the stents. The stent could maintain the basic structure and mechanical integrity at 6 months, and remained only approximately 26 % of the stent volume at 18 months, suggesting a desirable degradation rate. In general, the Zn-Cu-Mn alloy stent showed great advantages and prospects in clinical application.
{"title":"Biosafety and efficacy evaluation of a biodegradable Zn-Cu-Mn stent: A long-term study in porcine coronary artery","authors":"Yi Qian , Yan Chen , Jimiao Jiang , Jia Pei , Junfei Li , Jialin Niu , Jinzhou Zhu , Guangyin Yuan","doi":"10.1016/j.bioactmat.2024.11.022","DOIUrl":"10.1016/j.bioactmat.2024.11.022","url":null,"abstract":"<div><div>In this study, biodegradable Zn-Cu-Mn alloy stents were implanted into porcine coronary artery for 18 months, and the in vivo biosafety and efficacy as well as the degradation behavior were systematically studied. Results showed a rapid endothelialization of the target vessel was achieved at 1 month post-implantation. Although the lumen diameter loss and local inflammation were observed at the early stage, the stented blood vessel could gradually recover with time. The lumen diameter was already close to normal range at 12 months, indicating good bioefficacy of the stent. No adverse effect on blood indexes or local accumulation of Zn, Cu or Mn elements were found after implantation, neither the malapposition and thrombosis were observed, which exhibited good biosafety of the stents. The stent could maintain the basic structure and mechanical integrity at 6 months, and remained only approximately 26 % of the stent volume at 18 months, suggesting a desirable degradation rate. In general, the Zn-Cu-Mn alloy stent showed great advantages and prospects in clinical application.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"45 ","pages":"Pages 231-245"},"PeriodicalIF":18.0,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142699196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-25DOI: 10.1016/j.bioactmat.2024.11.030
Hun Jin Jeong, Lan Anh P. Hoang, Neeve Chen, Elen Zhu, Albert Wang, Bozhi Chen, Emma Y. Wang, Christopher L. Ricupero, Chang H. Lee
The interface between soft and hard tissues is constituted by a gradient change of cell types and matrix compositions that are optimally designed for proper load transmission and injury protection. In the musculoskeletal system, the soft-hard tissue interfaces at tendon-bone, ligament-bone, and meniscus-bone have been extensively researched as regenerative targets. Similarly, extensive research efforts have been made to guide the regeneration of multi-tissue complexes in periodontium. However, the other soft-hard tissue interfaces in the dental and craniofacial system have been somewhat neglected. This review discusses the clinical significance of developing regenerative strategies for soft-hard tissue interfaces in the dental and craniofacial system. It also discusses the research progress in the field focused on bioengineering approaches using 3D scaffolds equipped with spatially controlled bioactivities. The remaining challenges, future perspectives, and considerations for the clinical translation of bioactive scaffolds are also discussed.
{"title":"Engineering soft-hard tissue interfaces in dental and craniofacial system by spatially controlled bioactivities","authors":"Hun Jin Jeong, Lan Anh P. Hoang, Neeve Chen, Elen Zhu, Albert Wang, Bozhi Chen, Emma Y. Wang, Christopher L. Ricupero, Chang H. Lee","doi":"10.1016/j.bioactmat.2024.11.030","DOIUrl":"10.1016/j.bioactmat.2024.11.030","url":null,"abstract":"<div><div>The interface between soft and hard tissues is constituted by a gradient change of cell types and matrix compositions that are optimally designed for proper load transmission and injury protection. In the musculoskeletal system, the soft-hard tissue interfaces at tendon-bone, ligament-bone, and meniscus-bone have been extensively researched as regenerative targets. Similarly, extensive research efforts have been made to guide the regeneration of multi-tissue complexes in periodontium. However, the other soft-hard tissue interfaces in the dental and craniofacial system have been somewhat neglected. This review discusses the clinical significance of developing regenerative strategies for soft-hard tissue interfaces in the dental and craniofacial system. It also discusses the research progress in the field focused on bioengineering approaches using 3D scaffolds equipped with spatially controlled bioactivities. The remaining challenges, future perspectives, and considerations for the clinical translation of bioactive scaffolds are also discussed.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"45 ","pages":"Pages 246-256"},"PeriodicalIF":18.0,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142699197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In recent decades, 3D bioprinting has garnered significant research attention due to its ability to manipulate biomaterials and cells to create complex structures precisely. However, due to technological and cost constraints, the clinical translation of 3D bioprinted products (BPPs) from bench to bedside has been hindered by challenges in terms of personalization of design and scaling up of production. Recently, the emerging applications of artificial intelligence (AI) technologies have significantly improved the performance of 3D bioprinting. However, the existing literature remains deficient in a methodological exploration of AI technologies' potential to overcome these challenges in advancing 3D bioprinting toward clinical application. This paper aims to present a systematic methodology for AI-driven 3D bioprinting, structured within the theoretical framework of Quality by Design (QbD). This paper commences by introducing the QbD theory into 3D bioprinting, followed by summarizing the technology roadmap of AI integration in 3D bioprinting, including multi-scale and multi-modal sensing, data-driven design, and in-line process control. This paper further describes specific AI applications in 3D bioprinting's key elements, including bioink formulation, model structure, printing process, and function regulation. Finally, the paper discusses current prospects and challenges associated with AI technologies to further advance the clinical translation of 3D bioprinting.
{"title":"AI-driven 3D bioprinting for regenerative medicine: From bench to bedside","authors":"Zhenrui Zhang , Xianhao Zhou , Yongcong Fang , Zhuo Xiong , Ting Zhang","doi":"10.1016/j.bioactmat.2024.11.021","DOIUrl":"10.1016/j.bioactmat.2024.11.021","url":null,"abstract":"<div><div>In recent decades, 3D bioprinting has garnered significant research attention due to its ability to manipulate biomaterials and cells to create complex structures precisely. However, due to technological and cost constraints, the clinical translation of 3D bioprinted products (BPPs) from bench to bedside has been hindered by challenges in terms of personalization of design and scaling up of production. Recently, the emerging applications of artificial intelligence (AI) technologies have significantly improved the performance of 3D bioprinting. However, the existing literature remains deficient in a methodological exploration of AI technologies' potential to overcome these challenges in advancing 3D bioprinting toward clinical application. This paper aims to present a systematic methodology for AI-driven 3D bioprinting, structured within the theoretical framework of Quality by Design (QbD). This paper commences by introducing the QbD theory into 3D bioprinting, followed by summarizing the technology roadmap of AI integration in 3D bioprinting, including multi-scale and multi-modal sensing, data-driven design, and in-line process control. This paper further describes specific AI applications in 3D bioprinting's key elements, including bioink formulation, model structure, printing process, and function regulation. Finally, the paper discusses current prospects and challenges associated with AI technologies to further advance the clinical translation of 3D bioprinting.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"45 ","pages":"Pages 201-230"},"PeriodicalIF":18.0,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142699194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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