{"title":"Ex vivo SIM-AFM measurements reveal the spatial correlation of stiffness and molecular distributions in 3D living tissue","authors":"Itsuki Shioka , Ritsuko Morita , Rei Yagasaki , Duligengaowa Wuergezhen , Tadahiro Yamashita , Hironobu Fujiwara , Satoru Okuda","doi":"10.1016/j.actbio.2024.09.023","DOIUrl":"10.1016/j.actbio.2024.09.023","url":null,"abstract":"<div><div>Living tissues each exhibit a distinct stiffness, which provides cells with key environmental cues that regulate their behaviors. Despite this significance, our understanding of the spatiotemporal dynamics and the biological roles of stiffness in three-dimensional tissues is currently limited due to a lack of appropriate measurement techniques. To address this issue, we propose a new method combining upright structured illumination microscopy (USIM) and atomic force microscopy (AFM) to obtain precisely coordinated stiffness maps and biomolecular fluorescence images of thick living tissue slices. Using mouse embryonic and adult skin as a representative tissue with mechanically heterogeneous structures inside, we validate the measurement principle of USIM-AFM. Live measurement of tissue stiffness distributions revealed the highly heterogeneous mechanical nature of skin, including nucleated/enucleated epithelium, mesenchyme, and hair follicle, as well as the role of collagens in maintaining its integrity. Furthermore, quantitative analysis comparing stiffness distributions in live tissue samples with those in preserved tissues, including formalin-fixed and cryopreserved tissue samples, unveiled the distinct impacts of preservation processes on tissue stiffness patterns. This series of experiments highlights the importance of live mechanical testing of tissue-scale samples to accurately capture the true spatiotemporal variations in mechanical properties. Our USIM-AFM technique provides a new methodology to reveal the dynamic nature of tissue stiffness and its correlation with biomolecular distributions in live tissues and thus could serve as a technical basis for exploring tissue-scale mechanobiology.</div></div><div><h3>Statement of significance</h3><div>Stiffness, a simple mechanical parameter, has drawn attention in understanding the mechanobiological principles underlying the homeostasis and pathology of living tissues. To explore tissue-scale mechanobiology, we propose a technique integrating an upright structured illumination microscope and an atomic force microscope. This technique enables live measurements of stiffness distribution and fluorescent observation of thick living tissue slices. Experiments revealed the highly heterogeneous mechanical nature of mouse embryonic and adult skin in three dimensions and the previously unnoticed influences of preservation techniques on the mechanical properties of tissue at microscopic resolution. This study provides a new technical platform for live stiffness measurement and biomolecular observation of tissue-scale samples with micron-scale resolution, thus contributing to future studies of tissue- and organ-scale mechanobiology.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"189 ","pages":"Pages 351-365"},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142395905","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}
Acta BiomaterialiaPub Date : 2024-11-01DOI: 10.1016/j.actbio.2024.07.049
{"title":"Frederick J. Schoen, 2025 Acta Biomaterialia Gold Medal Award Recipient","authors":"","doi":"10.1016/j.actbio.2024.07.049","DOIUrl":"10.1016/j.actbio.2024.07.049","url":null,"abstract":"","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"189 ","pages":"Page 671"},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142657330","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}
Acta BiomaterialiaPub Date : 2024-11-01DOI: 10.1016/j.actbio.2024.08.044
Yunyun Xue , Chuyao Wang , Yu Zhao , Zihao Zhao , Ronglu Cui , Bin Du , Lifeng Fang , Jianyu Wang , Baoku Zhu
{"title":"Mixed-charge hyperbranched polymer nanoparticles with selective antibacterial action for fighting antimicrobial resistance","authors":"Yunyun Xue , Chuyao Wang , Yu Zhao , Zihao Zhao , Ronglu Cui , Bin Du , Lifeng Fang , Jianyu Wang , Baoku Zhu","doi":"10.1016/j.actbio.2024.08.044","DOIUrl":"10.1016/j.actbio.2024.08.044","url":null,"abstract":"<div><div>The escalating menace of antimicrobial resistance (AMR) presents a profound global threat to life and assets. However, the incapacity of metal ions/reactive oxygen species (ROS) or the indiscriminate intrinsic interaction of cationic groups to distinguish between bacteria and mammalian cells undermines the essential selectivity required in these nanomaterials for an ideal antimicrobial agent. Hence, we devised and synthesized a range of biocompatible mixed-charge hyperbranched polymer nanoparticles (MCHPNs) incorporating cationic, anionic, and neutral alkyl groups to effectively combat multidrug-resistant bacteria and mitigate AMR. This outcome stemmed from the structural, antibacterial activity, and biocompatibility analysis of seven MCHPNs, among which MCHPN7, with a ratio of cationic groups, anionic groups, and long alkyl chains at 27:59:14, emerged as the lead candidate. Importantly, owing to inherent differences in membrane potential among diverse species, alongside its nano-size (6–15 nm) and high hydrophilicity (<em>K<sub>ow</sub></em> = 0.04), MCHPN7 exhibited exceptional selective bactericidal effects over mammalian cells (selectivity index > 564) in vitro and in vivo. By inducing physical membrane disruption, MCHPN7 effectively eradicated antibiotic-resistant bacteria and significantly delayed the emergence of bacterial resistance. Utilized as a coating, MCHPN7 endowed initially inert surfaces with the ability to impede biofilm formation and mitigate infection-related immune responses in mouse models. This research heralds the advent of biocompatible polymer nanoparticles and harbors significant implications in our ongoing combat against AMR.</div></div><div><h3>Statement of significance</h3><div>The escalating prevalence of antimicrobial resistance (AMR) has been acknowledged as one of the most significant threats to global health.</div><div>Therefore, a series of mixed-charge hyperbranched polymer nanoparticles (MCHPNs) with selective antibacterial action were designed and synthesized. Owing to inherent differences in membrane potential among diverse species and high hydrophilicity (<em>K<sub>ow</sub></em> = 0.04), the optimal nanoparticles exhibited exceptional selective bactericidal effects over mammalian cells (selectivity index >564) and significantly delayed the emergence of bacterial resistance. Importantly, they endowed surfaces with the ability to impede biofilm formation and mitigate infection-related immune responses.</div><div>Furthermore, the above findings focus on addressing the problem of AMR in Post-Pandemic, which will for sure attract attention from both academic and industry research.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"189 ","pages":"Pages 545-558"},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142121304","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}
Acta BiomaterialiaPub Date : 2024-11-01DOI: 10.1016/j.actbio.2024.09.013
Changsheng Cai, Jun Shen
{"title":"The roles of migrasomes in immunity, barriers, and diseases","authors":"Changsheng Cai, Jun Shen","doi":"10.1016/j.actbio.2024.09.013","DOIUrl":"10.1016/j.actbio.2024.09.013","url":null,"abstract":"<div><div>Migrasomes are recently identified extracellular vesicles and organelles formed in conjunction with cell migration. They are situated at the rear of migrating cells, exhibit a circular or elliptical membrane-enclosed structure, and function as a new organelle. Migrasomes selectively sort intercellular components, mediating a cell migration-dependent release mechanism known as migracytosis and modulating cell–cell communication. Accumulated evidence clarifies migrasome formation processes and indicates their diverse functional roles. Migrasomes may also be potentially correlated with the occurrence, progression, and prognosis of certain diseases. Migrasomes’ involvement in physiological and pathological processes highlights their potential for expanding our understanding of biological procedures and as a target in clinical therapy. However, the precise mechanisms and full extent of their involvement in immunity, barriers, and diseases remain unclear. This review aimed to provide a comprehensive overview of the roles of migrasomes in human immunity and barriers, in addition to providing insights into their impact on human diseases.</div></div><div><h3>Statement of significance</h3><div>Migrasomes, newly identified extracellular vesicles and organelles, form during cell migration and are located at the rear of migrating cells. These circular or elliptical structures mediate migracytosis, selectively sorting intercellular components and modulating cell–cell communication. Evidence suggests diverse functional roles for migrasomes, including potential links to disease occurrence, progression, and prognosis. Their involvement in physiological and pathological processes highlights their significance in understanding biological procedures and potential clinical therapies. However, their exact mechanisms in immunity, barriers, and diseases remain unclear. This review provides an overview of migrasomes' roles in human immunity and barriers, and their impact on diseases.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"189 ","pages":"Pages 88-102"},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303141","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}
Acta BiomaterialiaPub Date : 2024-11-01DOI: 10.1016/j.actbio.2024.09.034
Xiongbo Song , Jinwen Xiao , Xiaojun Ai , Yankun Li , Li Sun , Long Chen
{"title":"An injectable thermosensitive hydrogel delivering M2 macrophage-derived exosomes alleviates osteoarthritis by promoting synovial lymphangiogenesis","authors":"Xiongbo Song , Jinwen Xiao , Xiaojun Ai , Yankun Li , Li Sun , Long Chen","doi":"10.1016/j.actbio.2024.09.034","DOIUrl":"10.1016/j.actbio.2024.09.034","url":null,"abstract":"<div><div>Osteoarthritis (OA) is a prevalent chronic degenerative disease affecting millions worldwide, with current treatment measures lacking efficacy in slowing disease progression. The synovial lymphatic system (SLS) has emerged as a crucial player in OA pathogenesis, with compromised drainage function contributing to disease advancement. Lymphatic endothelial cells (LECs) within the SLS are influenced by synovial macrophages, whose precise impact on LEC function remains unclear. Exosomes released by macrophages may serve as mediators of this interaction, with potential implications for OA progression. Here, we propose that polarized macrophages modulate LEC activity via exosome release in synovial tissue, with M2 macrophage-derived exosomes (M2<sup>Exo</sup>) promoting LEC proliferation, migration, and lymphangiogenesis, potentially offering a therapeutic avenue for OA. Moreover, we developed an injectable thermosensitive hydrogel with the characteristic of sustained release of M2<sup>Exo</sup> for alleviating OA. The hydrogel was prepared by dynamically linking hyaluronic acid (HA) and Pluronic F-127 and loading M2<sup>Exo</sup>, termed as M2<sup>Exo</sup> loaded HP hydrogel. The <em>in vitro</em> and <em>in vivo</em> experiments showed that M2<sup>Exo</sup> loaded HP hydrogel exhibits a controlled release profile of exosomes, thereby efficaciously fostering synovial lymphangiogenesis and enhancing synovial lymphatic drainage functionality under OA conditions, thus alleviating OA progression, and providing promising insights into OA therapeutic strategies.</div></div><div><h3>Statement of significance</h3><div>Osteoarthritis (OA) is a widespread degenerative disease with limited effective treatments to halt its progression. This research highlights the critical role of the synovial lymphatic system (SLS) in OA, focusing on how macrophage-derived exosomes influence lymphatic endothelial cell (LEC) function. We propose that M2 macrophage-derived exosomes (M2<sup>Exo</sup>) enhance LEC activity, promoting lymphangiogenesis, and offering a therapeutic approach for OA. Furthermore, we developed an injectable thermosensitive hydrogel (M2<sup>Exo</sup> loaded HP hydrogel) for sustained M2<sup>Exo</sup> release. Our <em>in vitro</em> and <em>in vivo</em> experiments demonstrate that this hydrogel supports synovial lymphangiogenesis and improves lymphatic drainage, effectively alleviating OA progression. This study presents significant advancements in OA therapy, offering new insights into its management.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"189 ","pages":"Pages 130-142"},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334134","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}
Acta BiomaterialiaPub Date : 2024-11-01DOI: 10.1016/j.actbio.2024.09.049
Mohammad Mehri , Hossein Sharifi , Charles K. Mann , Alexus L. Rockward , Kenneth S. Campbell , Lik Chuan Lee , Jonathan F. Wenk
{"title":"Multiscale fiber remodeling in the infarcted left ventricle using a stress-based reorientation law","authors":"Mohammad Mehri , Hossein Sharifi , Charles K. Mann , Alexus L. Rockward , Kenneth S. Campbell , Lik Chuan Lee , Jonathan F. Wenk","doi":"10.1016/j.actbio.2024.09.049","DOIUrl":"10.1016/j.actbio.2024.09.049","url":null,"abstract":"<div><div>The organization of myofibers and extra cellular matrix within the myocardium plays a significant role in defining cardiac function. When pathological events occur, such as myocardial infarction (MI), this organization can become disrupted, leading to degraded pumping performance. The current study proposes a multiscale finite element (FE) framework to determine realistic fiber distributions in the left ventricle (LV). This is achieved by implementing a stress-based fiber reorientation law, which seeks to align the fibers with local traction vectors, such that contractile force and load bearing capabilities are maximized. By utilizing the total stress (passive and active), both myofibers and collagen fibers are reoriented. Simulations are conducted to predict the baseline fiber configuration in a normal LV as well as the adverse fiber reorientation that occurs due to different size MIs. The baseline model successfully captures the transmural variation of helical fiber angles within the LV wall, as well as the transverse fiber angle variation from base to apex. In the models of MI, the patterns of fiber reorientation in the infarct, border zone, and remote regions closely align with previous experimental findings, with a significant increase in fibers oriented in a left-handed helical configuration and increased dispersion in the infarct region. Furthermore, the severity of fiber reorientation and impairment of pumping performance both showed a correlation with the size of the infarct. The proposed multiscale modeling framework allows for the effective prediction of adverse remodeling and offers the potential for assessing the effectiveness of therapeutic interventions in the future.</div></div><div><h3>Statement of Significance</h3><div>The organization of muscle and collagen fibers within the heart plays a significant role in defining cardiac function. This organization can become disrupted after a heart attack, leading to degraded pumping performance. In the current study, we implemented a stress-based fiber reorientation law into a computer model of the heart, which seeks to realign the fibers such that contractile force and load bearing capabilities are maximized. The primary goal was to evaluate the effects of different sized heart attacks. We observed substantial fiber remodeling in the heart, which matched experimental observations. The proposed computational framework allows for the effective prediction of adverse remodeling and offers the potential for assessing the effectiveness of therapeutic interventions in the future.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"189 ","pages":"Pages 337-350"},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142373680","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}
Acta BiomaterialiaPub Date : 2024-11-01DOI: 10.1016/j.actbio.2024.09.043
Giuseppe Sciumè , Karine Guevorkian , Pierre Nassoy
{"title":"A bi-component model to assess the rheology of soft cellular aggregates probed using the micropipette aspiration technique","authors":"Giuseppe Sciumè , Karine Guevorkian , Pierre Nassoy","doi":"10.1016/j.actbio.2024.09.043","DOIUrl":"10.1016/j.actbio.2024.09.043","url":null,"abstract":"<div><div>The micro-pipette aspiration technique is a classical experiment used to characterize the physical properties of inert fluids and biological soft materials such as cellular aggregates. The physical parameters of the fluid, as viscosity and interfacial tension, are obtained by studying how the fluid enters the pipette when the suction pressure is increased and how it relaxes when the suction pressure is put to zero. A mathematical model representative of the experiment is needed to extrapolate the physical parameters of the fluid-like matter; however, for biological materials as cells or cell aggregates mathematical models are always based on strong starting hypotheses that impact the significance of the identified parameters. In this article, starting from the bi-constituent nature of the cell aggregate, we derive a general mathematical model based of a Cahn–Hilliard–Navier–Stokes set of equations. The model is applied to describe quantitatively the aspiration-retraction dynamics of a cell-aggregate into and out of a pipette. We demonstrate the predictive capability of the model and highlight the impact of the assumptions made on the identified parameters by studying two cases: one with a non-wetting condition between the cells and the wall of the pipette (classical assumption in the literature) and the second one, which is more realistic, with a partial wetting condition (contact angle <em>θ<sub>s</sub></em> = 150°). Furthermore, our results provide a purely physical explanation to the asymmetry between the aspiration and retraction responses which is alternative to the proposed hypothesis of an mechano-responsive alteration of the surface tension of the cell aggregate.</div></div><div><h3>Statement of significance</h3><div>Our study introduces a general mathematical model, based on the Cahn-Hilliard-Navier-Stokes equations, tailored to model micro-pipette aspiration of cell aggregates. The model accounts for the multi-component structure of the cell aggregate and its intrinsic viscoelastic rheology. By challenging prevailing assumptions, particularly regarding perfect non-wetting conditions and the mechano-responsive alteration of cell surface tension, we demonstrate the reliability of the mathematical model and elucidate the mechanisms at play, offering a purely physical explanation for observed asymmetries between the aspiration and retraction stages of the experiment.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"189 ","pages":"Pages 449-460"},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142373745","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}
Acta BiomaterialiaPub Date : 2024-11-01DOI: 10.1016/j.actbio.2024.10.021
Patrick C. Ralph , Sung-Woo Choi , Min Jung Baek , Sang Jin Lee
{"title":"Regenerative medicine approaches for the treatment of spinal cord injuries: Progress and challenges","authors":"Patrick C. Ralph , Sung-Woo Choi , Min Jung Baek , Sang Jin Lee","doi":"10.1016/j.actbio.2024.10.021","DOIUrl":"10.1016/j.actbio.2024.10.021","url":null,"abstract":"<div><div>Spinal cord injury (SCI) is a profound medical condition that significantly hampers motor function, imposing substantial limitations on daily activities and exerting a considerable financial burden on patients and their families. The constrained regenerative capacity of endogenous spinal cord tissue, exacerbated by the inflammatory response following the initial trauma, poses a formidable obstacle to effective therapy. Recent advancements in the field, stem cells, biomaterials, and molecular therapy, show promising outcomes. This review provides a comprehensive analysis of tissue engineering and regenerative medicine approaches for SCI treatment, including cell transplantation, tissue-engineered construct implantation, and other potential therapeutic strategies. Additionally, it sheds light on preclinical animal studies and recent clinical trials incorporating these modalities, providing a glimpse into the evolving landscape of SCI management.</div></div><div><h3>Statement of Significance</h3><div>The investigation into spinal cord injury (SCI) treatments focuses on reducing long-term impacts by targeting scar inhibition and enhancing regeneration through stem cells, with or without growth factors. Induced pluripotent stem cells (iPSCs) show promise for autologous use, with clinical trials confirming their safety. Challenges include low cell viability and difficulty in targeted differentiation. Biomaterial scaffolds hold potential for improving cell viability and integration, and extracellular vesicles (EVs) are emerging as a novel therapy. While EV research is in its early stages, stem cell trials demonstrate safety and potential recovery. Advancing tissue engineering approaches with biomaterial scaffolds is crucial for human trials.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"189 ","pages":"Pages 57-72"},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482767","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}
Acta BiomaterialiaPub Date : 2024-11-01DOI: 10.1016/j.actbio.2024.09.056
Xiaoqing Zhang , Guangtao Zhao , Tianyi Ma , Craig A. Simmons , J Paul Santerre
{"title":"A critical review on advances and challenges of bioprinted cardiac patches","authors":"Xiaoqing Zhang , Guangtao Zhao , Tianyi Ma , Craig A. Simmons , J Paul Santerre","doi":"10.1016/j.actbio.2024.09.056","DOIUrl":"10.1016/j.actbio.2024.09.056","url":null,"abstract":"<div><div>Myocardial infarction (MI), which causes irreversible myocardium necrosis, affects 0.25 billion people globally and has become one of the most significant epidemics of our time. Over the past few years, bioprinting has moved beyond a concept of simply incorporating cells into biomaterials, to strategically defining the microenvironment (e.g., architecture, biomolecular signalling, mechanical stimuli, etc.) within which the cells are printed. Among the different bioprinting applications, myocardial repair is a field that has seen some of the most significant advances towards the management of the repaired tissue microenvironment. This review critically assesses the most recent biomedical innovations being carried out in cardiac patch bioprinting, with specific considerations given to the biomaterial design parameters, growth factors/cytokines, biomechanical and bioelectrical conditioning, as well as innovative biomaterial-based “4D” bioprinting (3D scaffold structure + temporal morphology changes) of myocardial tissues, immunomodulation and sustained delivery systems used in myocardium bioprinting. Key challenges include the ability to generate large quantities of cardiac cells, achieve high-density capillary networks, establish biomaterial designs that are comparable to native cardiac extracellular matrix, and manage the sophisticated systems needed for combining cardiac tissue microenvironmental cues while simultaneously establishing bioprinting technologies yielding both high-speed and precision. This must be achieved while considering quality assurance towards enabling reproducibility and clinical translation. Moreover, this manuscript thoroughly discussed the current clinical translational hurdles and regulatory issues associated with the post-bioprinting evaluation, storage, delivery and implantation of the bioprinted myocardial patches. Overall, this paper provides insights into how the clinical feasibility and important regulatory concerns may influence the design of the bioink (biomaterials, cell sources), fabrication and post-fabrication processes associated with bioprinting of the cardiac patches. This paper emphasizes that cardiac patch bioprinting requires extensive collaborations from imaging and 3D modelling technical experts, biomaterial scientists, additive manufacturing experts and healthcare professionals. Further, the work can also guide the field of cardiac patch bioprinting moving forward, by shedding light on the potential use of robotics and automation to increase productivity, reduce financial cost, and enable standardization and true commercialization of bioprinted cardiac patches.</div></div><div><h3>Statement of significance</h3><div>The manuscript provides a critical review of important themes currently pursued for heart patch bioprinting, including critical biomaterial design parameters, physiologically-relevant cardiac tissue stimulations, and newly emerging cardiac tissue bioprinting strategies. This revie","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"189 ","pages":"Pages 1-24"},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142395893","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}