{"title":"Advanced non-fluoride approaches to dental enamel remineralization: The next level in enamel repair management","authors":"Bernd Grohe , Silvia Mittler","doi":"10.1016/j.bbiosy.2021.100029","DOIUrl":"10.1016/j.bbiosy.2021.100029","url":null,"abstract":"<div><p>In modern dentistry, a minimally invasive management of early caries lesions or early-stage erosive tooth wear (ETW) with synthetic remineralization systems has become indispensable. In addition to fluoride, which is still the non-plus-ultra in these early caries/ETW treatments, a number of new developments are in the test phase or have already been commercialized. Some of these systems claim that they are comparable or even superior to fluoride in terms of their ability to remineralize enamel. Besides, their use can help avoid some of the risks associated with fluoride and support treatments of patients with a high risk of caries. Two individual non-fluoride systems can be distinguished; intrinsic and extrinsic remineralization approaches. Intrinsic (protein/peptide) systems adsorb to hydroxyapatite crystals/organics located within enamel prisms and accumulate endogenous calcium and phosphate ions from saliva, which ultimately leads to the re-growth of enamel crystals. Extrinsic remineralization systems function on the basis of the external (non-saliva) supply of calcium and phosphate to the crystals to be re-grown. This article, following an introduction into enamel (re)mineralization and fluoride-assisted remineralization, discusses the requirements for non-fluoride remineralization systems, particularly their mechanisms and challenges, and summarizes the findings that underpin the most promising advances in enamel remineralization therapy.</p></div>","PeriodicalId":72379,"journal":{"name":"Biomaterials and biosystems","volume":"4 ","pages":"Article 100029"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9934497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9336298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Michael A. Bellio , Cassie Bennett , Alissa Arango , Aisha Khan , Xiumin Xu , Cesar Barrera , Vincent Friedewald , Maria Ines Mitrani
{"title":"Proof-of-concept trial of an amniotic fluid-derived extracellular vesicle biologic for treating high risk patients with mild-to-moderate acute COVID-19 infection","authors":"Michael A. Bellio , Cassie Bennett , Alissa Arango , Aisha Khan , Xiumin Xu , Cesar Barrera , Vincent Friedewald , Maria Ines Mitrani","doi":"10.1016/j.bbiosy.2021.100031","DOIUrl":"10.1016/j.bbiosy.2021.100031","url":null,"abstract":"<div><p>A pandemic brought on by COVID-19 has created a scalable health crisis. The search to help alleviate COVID-19-related complications through therapeutics has become a necessity. Zofin is an investigational, acellular biologic derived from full-term perinatal amniotic fluid that contains extracellular vesicles. Extracellular nanoparticles as such have been studied for their immunomodulatory benefits via cellular therapeutics and, if applied to COVID-19-related inflammation, could benefit patient outcome. Subjects (<em>n</em> = 8) experiencing mild-to-moderate COVID-19 symptoms were treated with the experimental intervention. Complete blood count, complete metabolic panel, inflammatory biomarkers, and absolute lymphocyte counts were recorded prior to and on days 4, 8, 14, 21, and 30 as markers of disease progression. Additionally, chest x-rays were taken of the patients prior to and on days 8 and 30. Patients experienced no serious adverse events. All COVID-19-associated symptoms resolved or became stable with no indication of disease worsening as found by patient and chest x-ray reports. Inflammatory biomarkers (CRP, IL-6, TNF-<span><math><mi>α</mi></math></span>) and absolute lymphocyte counts improved throughout the study period. Findings from a proof-of-concept, expanded access trial for COVID-19 patients prove the acellular biologic is safe and potentially effective to prevent disease progression in a high-risk COVID-19 population with mild-to-moderate symptoms.</p></div>","PeriodicalId":72379,"journal":{"name":"Biomaterials and biosystems","volume":"4 ","pages":"Article 100031"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/be/7c/main.PMC8611818.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10741832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Olivia R.M. Bagshaw , Fereshteh Moradi , Christopher S. Moffatt , Hillary A. Hettwer , Ping Liang , Jeremy Goldman , Jaroslaw W. Drelich , Jeffrey A. Stuart
{"title":"Bioabsorbable metal zinc differentially affects mitochondria in vascular endothelial and smooth muscle cells","authors":"Olivia R.M. Bagshaw , Fereshteh Moradi , Christopher S. Moffatt , Hillary A. Hettwer , Ping Liang , Jeremy Goldman , Jaroslaw W. Drelich , Jeffrey A. Stuart","doi":"10.1016/j.bbiosy.2021.100027","DOIUrl":"10.1016/j.bbiosy.2021.100027","url":null,"abstract":"<div><p>Zinc is an essential trace element having various structural, catalytic and regulatory interactions with an estimated 3000 proteins. Zinc has drawn recent attention for its use, both as pure metal and alloyed, in arterial stents due to its biodegradability, biocompatibility, and low corrosion rates. Previous studies have demonstrated that zinc metal implants prevent the development of neointimal hyperplasia, which is a common cause of restenosis following coronary intervention. This suppression appears to be smooth muscle cell-specific, as reendothelization of the neointima is not inhibited. To better understand the basis of zinc's differential effects on rat aortic smooth muscle (RASMC) versus endothelial (RAENDO) cells, we conducted a transcriptomic analysis of both cell types following one-week continuous treatment with 5 µM or 50 µM zinc. This analysis indicated that genes whose protein products regulate mitochondrial functions, including oxidative phosphorylation and fusion/fission, are differentially affected by zinc in the two cell types. To better understand this, we performed Seahorse metabolic flux assays and quantitative imaging of mitochondrial networks in both cell types. Zinc treatment differently affected energy metabolism and mitochondrial structure/function in the two cell types. For example, both basal and maximal oxygen consumption rates were increased by zinc in RASMC but not in RAENDO. Zinc treatment increased apparent mitochondrial fusion in RASMC cells but increased mitochondrial fission in RAENDO cells. These results provide some insight into the mechanisms by which zinc treatment differently affects the two cell types and this information is important for understanding the role of zinc treatment in vascular cells and improving its use in biodegradable metal implants.</p></div>","PeriodicalId":72379,"journal":{"name":"Biomaterials and biosystems","volume":"4 ","pages":"Article 100027"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbiosy.2021.100027","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9336300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mitochondria-targeted nanoparticles (mitoNANO): An emerging therapeutic shortcut for cancer","authors":"Tanveer A. Tabish , Michael R. Hamblin","doi":"10.1016/j.bbiosy.2021.100023","DOIUrl":"10.1016/j.bbiosy.2021.100023","url":null,"abstract":"<div><p>The early understanding of mitochondria posited that they were ‘innocent organelles’ solely devoted to energy production and utilisation. Intriguingly, recent findings have outlined in detail the ‘modern-day’ view that mitochondria are an important but underappreciated drug target. Mitochondria have been implicated in the pathophysiology of many human diseases, ranging from neurodegenerative disorders and cardiovascular diseases to infections and cancer. It is now clear that normal mitochondrial function involves the building blocks of a cell to generate lipids, proteins and nucleic acids thereby facilitating cell growth. On the other hand, mitochondrial dysfunction reprograms crucial cellular functions into pathological pathways, and is considered as an integral hallmark of cancer. Therefore, strategies to target mitochondria can provide a wealth of new therapeutic approaches in the fight against cancer, by overcoming a number of problems associated with conventional pharmaceutical drugs, including low solubility, poor bioavailability and non-selective biodistribution. The combination of nanoparticles with ‘classical’ chemotherapeutic drugs to create biocompatible, multifunctional mitochondria-targeted nanoplatforms has been recently studied. This approach is now rapidly expanding for targeted drug delivery systems, and for hybrid nanostructures that can be activated with light (photodynamic and/or photothermal therapy). The selective delivery of nanoparticles to mitochondria is an elegant shortcut to more selective, targeted, and safer cancer treatment. We propose that the use of nanoparticles to target mitochondria be termed “mitoNANO”. The present minireview sheds light on the design and application of mitoNANO as advanced cancer therapeutics, that may overcome drug resistance and show fewer side effects.</p></div>","PeriodicalId":72379,"journal":{"name":"Biomaterials and biosystems","volume":"3 ","pages":"Article 100023"},"PeriodicalIF":0.0,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbiosy.2021.100023","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9336271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ehsan Akbari , Griffin B. Spychalski , Miles M. Menyhert , Kaushik K. Rangharajan , Joseph W. Tinapple , Shaurya Prakash , Jonathan W. Song
{"title":"Endothelial barrier function is co-regulated at vessel bifurcations by fluid forces and sphingosine-1-phosphate","authors":"Ehsan Akbari , Griffin B. Spychalski , Miles M. Menyhert , Kaushik K. Rangharajan , Joseph W. Tinapple , Shaurya Prakash , Jonathan W. Song","doi":"10.1016/j.bbiosy.2021.100020","DOIUrl":"10.1016/j.bbiosy.2021.100020","url":null,"abstract":"<div><p>Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid mediator of endothelial barrier function. Prior studies have implicated mechanical stimulation due to intravascular laminar shear stress in co-regulating S1P signaling in endothelial cells (ECs). Yet, vascular networks in vivo consist of vessel bifurcations, and this geometry generates hemodynamic forces at the bifurcation point distinct from laminar shear stress. However, the role of these forces at vessel bifurcations in regulating S1P-dependent endothelial barrier function is not known. In this study, we implemented a microfluidic platform that recapitulates the flow dynamics of vessel bifurcations with in situ quantification of the permeability of microvessel analogues. Co-application of S1P with impinging bifurcated fluid flow, which is characterized by approximately zero shear stress and 38 dyn•cm<sup>−2</sup> stagnation pressure at the vessel bifurcation point, promotes vessel stabilization. Similarly, co-treatment of S1P with 3 dyn•cm<sup>−2</sup> laminar shear stress is also protective of endothelial barrier function. Moreover, it is shown that vessel stabilization due to bifurcated fluid flow and laminar shear stress is dependent on S1P receptor 1 or 2 signaling. Collectively, these findings demonstrate the endothelium-protective function of fluid forces at vessel bifurcations and their involvement in coordinating S1P-dependent regulation of vessel permeability.</p></div>","PeriodicalId":72379,"journal":{"name":"Biomaterials and biosystems","volume":"3 ","pages":"Article 100020"},"PeriodicalIF":0.0,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbiosy.2021.100020","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10758973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Biodegradable nanoparticulate co-delivery of flavonoid and doxorubicin: Mechanistic exploration and evaluation of anticancer effect in vitro and in vivo","authors":"Iliyas Khan , Bibekananda Sarkar , Gaurav Joshi , Kartik T. Nakhate , Ajazuddin , Anil K. Mantha , Raj Kumar , Ankur Kaul , Shubhra Chaturvedi , Anil K. Mishra , Umesh Gupta","doi":"10.1016/j.bbiosy.2021.100022","DOIUrl":"10.1016/j.bbiosy.2021.100022","url":null,"abstract":"<div><p>The proposed study involves delivering drug/bioactive using a single nanoplatform based on poly lactic-co-glycolic acid (PLGA) for better efficacy, synergistic effect, and reduced toxicity. PLGA was conjugated to doxorubicin (D1), and this conjugate was used for encapsulation of naringenin (D2) to develop naringenin loaded PLGA-doxorubicin nanoparticles (PDNG). The PDNG NPs were 165.4 ± 4.27 nm in size, having 0.112 ± 0.035 PDI, with -10.1 ± 2.74 zeta potential. The surface morphology was confirmed through transmission electron microscopy (TEM) and atomic force microscopy (AFM). The <em>in vitro</em> studies revealed that PDNG NPs exhibited selective anticancer potential in breast cancer cells, and induced apoptosis with S-phase inhibition <em>via</em> an increase in intrinsic reactive oxygen species (ROS) and altering the mitochondrial potential. The results also signified the efficient uptake of nanoparticles encapsulated drugs by cells besides elevating the caspase level suggesting programmed cell death induction upon treatment. <em>In vivo</em> studies results revealed better half-life (27.35 ± 1.58 and 11.98 ± 1.21 h for doxorubicin and naringenin) with higher plasma drug concentration. <em>In vivo</em> biodistribution study was also in accordance with the <em>in vitro</em> studies and in line with the <em>in vivo</em> pharmacokinetic. <em>In vivo</em> tumor regression assay portrayed that the formulation PDNG halts the tumor growth and lessen the tumor volume with the stable bodyweight of the mice. Conclusively, the dual delivery approach was beneficial and highly effective against tumor-induced mice.</p></div>","PeriodicalId":72379,"journal":{"name":"Biomaterials and biosystems","volume":"3 ","pages":"Article 100022"},"PeriodicalIF":0.0,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbiosy.2021.100022","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9336276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Daniel Nisakar Meenakshi Sundaram , Cezary Kucharski , Remant Bahadur KC , Ibrahim Oğuzhan Tarman , Hasan Uludağ
{"title":"Polymeric siRNA delivery targeting integrin-β1 could reduce interactions of leukemic cells with bone marrow microenvironment","authors":"Daniel Nisakar Meenakshi Sundaram , Cezary Kucharski , Remant Bahadur KC , Ibrahim Oğuzhan Tarman , Hasan Uludağ","doi":"10.1016/j.bbiosy.2021.100021","DOIUrl":"10.1016/j.bbiosy.2021.100021","url":null,"abstract":"<div><p>Uncontrolled proliferation of the myeloid cells due to <em>BCR-ABL</em> fusion has been successfully treated with tyrosine kinase inhibitors (TKIs), which improved the survival rate of Chronic Myeloid Leukemia (CML) patients. However, due to interactions of CML cells with bone marrow microenvironment, sub-populations of CML cells could become resistant to TKI treatment. Since integrins are major cell surface molecules involved in such interactions, the potential of silencing integrin-β1 on CML cell line K562 cells was explored using short interfering RNA (siRNA) delivered through lipid-modified polyethyleneimine (PEI) polymers. Reduction of integrin-β1 in K562 cells decreased cell adhesion towards human bone marrow stromal cells and to fibronectin, a major extracellular matrix protein for which integrin-β1 is a primary receptor. Interaction of K562 cells with fibronectin decreased the sensitivity of the cells to BCR-ABL siRNA treatment, but a combinational treatment with integrin-β1 and BCR-ABL siRNAs significantly reduced colony forming ability of the cells. Moreover, integrin-β1 silencing enhanced the detachment of K562 cells from hBMSC samples (2 out of 4 samples), which could make them more susceptible to TKIs. Therefore, the polymeric-siRNA delivery targeting integrin-β1 could be beneficial to reduce interactions with bone marrow microenvironment, aiding in the response of CML cells to therapeutic treatment.</p></div>","PeriodicalId":72379,"journal":{"name":"Biomaterials and biosystems","volume":"3 ","pages":"Article 100021"},"PeriodicalIF":0.0,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbiosy.2021.100021","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9321509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"How can molecular dynamics simulations assist with gene medicines?","authors":"Hasan Uludağ , Tian Tang","doi":"10.1016/j.bbiosy.2021.100014","DOIUrl":"10.1016/j.bbiosy.2021.100014","url":null,"abstract":"<div><p>Molecular Dynamics (MD) simulations can provide a glimpse of complex atomistic and molecular events at the interface of biomaterials and biosystems. Gene therapy efforts that deploy biomaterial mediated delivery of nucleic acids could benefit immensely from such MD simulations. These efforts most commonly employ supramolecular assembly whose structure is highly dynamic and influential in the final outcomes. By careful analysis of the behavior of constituting elements, one can visualize the assembly as it makes its way though biosystems. We highlight the beneficial information to be gained from MD studies in this short perspective and outline a vision for future activity in the field.</p></div>","PeriodicalId":72379,"journal":{"name":"Biomaterials and biosystems","volume":"2 ","pages":"Article 100014"},"PeriodicalIF":0.0,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbiosy.2021.100014","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9336308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stuart B. Goodman MD PhD , Stefan Zwingenberger MD
{"title":"Concentrated autologous bone marrow aspirate is not “stem cell” therapy in the repair of nonunions and bone defects","authors":"Stuart B. Goodman MD PhD , Stefan Zwingenberger MD","doi":"10.1016/j.bbiosy.2021.100017","DOIUrl":"10.1016/j.bbiosy.2021.100017","url":null,"abstract":"<div><p>Autogenous bone grafting is the gold standard for replacing large bone defects. Due to limitations in the quantity and quality of harvested bone from the iliac crest, and the potential associated morbidity, the technique of cell grafting has been developed. Autogenous bone marrow aspirate is concentrated (so called BMAC) and delivered locally to the intended site with minimally invasive techniques. However, there are only about 1 in 30,000 Colony Forming Unit-Fibroblast (CFU-F) progenitor cells in unconcentrated iliac crest aspirate. Current techniques for cell concentration only increase these numbers by about 5-fold. Thus, BMAC is not equivalent to “stem cell therapy”.</p></div>","PeriodicalId":72379,"journal":{"name":"Biomaterials and biosystems","volume":"2 ","pages":"Article 100017"},"PeriodicalIF":0.0,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbiosy.2021.100017","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9321541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cell engineering techniques improve pharmacology of cellular therapeutics","authors":"Kaini Liang, Yanan Du","doi":"10.1016/j.bbiosy.2021.100016","DOIUrl":"10.1016/j.bbiosy.2021.100016","url":null,"abstract":"<div><p>Despite the rapid growth of clinical trials for cellular therapy worldwide, their clinical success is still afflicted with formidable challenges demanding conceptual and technological overhaul. Pharmacology, which is conventionally divided into pharmacokinetics (PK) and pharmacodynamics (PD) in drug discovery have emerged as a prominent research direction to elucidate the cell fate and ensure the efficacy and safety of the therapeutic cells. Herein, we concisely present the dilemmas of cellular therapies, the concept of cell pharmacology, and the advances in cell engineering that leverage the cell formulation technologies to modulate cellular PK/PD for development of more cogent and versatile cell-based therapies.</p></div>","PeriodicalId":72379,"journal":{"name":"Biomaterials and biosystems","volume":"2 ","pages":"Article 100016"},"PeriodicalIF":0.0,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbiosy.2021.100016","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9321546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}