{"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}
{"title":"Current good manufacturing practice considerations for mesenchymal stromal cells as therapeutic agents","authors":"Clara Sanz-Nogués, Timothy O'Brien","doi":"10.1016/j.bbiosy.2021.100018","DOIUrl":"10.1016/j.bbiosy.2021.100018","url":null,"abstract":"<div><p>Producing human mesenchymal stromal cells (MSCs) for clinical use requires adherence to current good manufacturing practice (cGMP) standards. This is necessary for ensuring standardization and reproducibility through the manufacturing process, but also, for product quality and safety. However, the large-scale production of clinical-grade MSCs possesses unique regulatory challenges and hurdles related to the heterogeneous nature of MSC cultures as well as the complex manufacturing process. Following is a compilation of the major issues encountered in the manufacturing of MSCs for clinical use, and our views on the optimal characteristics of the final MSC product.</p></div>","PeriodicalId":72379,"journal":{"name":"Biomaterials and biosystems","volume":"2 ","pages":"Article 100018"},"PeriodicalIF":0.0,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbiosy.2021.100018","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9321543","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":"Current interpretations on the in vivo response of bone to additively manufactured metallic porous scaffolds: A review","authors":"Joseph Deering , Kathryn Grandfield","doi":"10.1016/j.bbiosy.2021.100013","DOIUrl":"10.1016/j.bbiosy.2021.100013","url":null,"abstract":"<div><p>Recent advances in the field of metallic additive manufacturing have expanded production capabilities for bone implants to include porous lattice structures. While traditional models of <em>de novo</em> bone formation can be applied to fully dense implant materials, their applicability to the interior of porous materials has not been well-characterized. Unlike other reviews that focus on materials and mechanical properties of lattice structures, this review compiles biological performance from <em>in vivo</em> studies in pre-clinical models only. First, we introduce the most common lattice geometry designs employed <em>in vivo</em> and discuss some of their fabrication advantages and limitations. Then lattice geometry is correlated to quantitative (histomorphometric) and qualitative (histological) assessments of osseointegration. We group studies according to two common implant variables: pore size and percent porosity, and explore the extent of osseointegration using common measures, including bone-implant contact (BIC), bone area (BA), bone volume/total volume (BV/TV) and biomechanical stability, for various animal models and implantation times. Based on this, trends related to <em>in vivo</em> bone formation on the interior of lattice structures are presented. Common challenges with lattice structures are highlighted, including nonuniformity of bone growth through the entirety of the lattice structure due to occlusion effects and avascularity. This review paper identifies a lack of systematic <em>in vivo</em> studies on porous AM implants to target optimum geometric design, including pore shape, size, and percent porosity in controlled animal models and critical-sized defects. Further work focusing on surface modification strategies and systematic geometric studies to homogenize <em>in vivo</em> bone growth through the scaffold interior are recommended to increase implant stability in the early stages of osseointegration.</p></div>","PeriodicalId":72379,"journal":{"name":"Biomaterials and biosystems","volume":"2 ","pages":"Article 100013"},"PeriodicalIF":0.0,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbiosy.2021.100013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9321542","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":"Chemical modification strategies to prepare advanced protein-based biomaterials","authors":"Maria C. Gomes, João F. Mano","doi":"10.1016/j.bbiosy.2021.100010","DOIUrl":"10.1016/j.bbiosy.2021.100010","url":null,"abstract":"<div><p>Nature is a superb source of inspiration when it comes to the development of biomaterials. Proteins, an exquisite asset virtually involved in all biological functions, are envisioned as a biomaterial due to their ability to be chemically modified. Owing to the rich chemical repertoire provided by the side chains and C-/N-terminus present in their backbone, scientists are pursuing chemical ways to upgrade isolated proteins, while maintaining their biological activity or relevant structural properties. By inserting chemical motifs, the crosslinking capability of proteins and capability to attach biochemical and molecular groups can be controlled yielding nano to macro constructs and hydrogels with improved physicochemical and mechanical properties. These cutting-edge approaches elevate the potential use of proteins as promising biomaterials for biotechnology and biomedicine.</p></div>","PeriodicalId":72379,"journal":{"name":"Biomaterials and biosystems","volume":"1 ","pages":"Article 100010"},"PeriodicalIF":0.0,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbiosy.2021.100010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9322012","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":"The convergence of high-tech emerging technologies into the next stage of organ-on-a-chips","authors":"Alessandro Polini , Lorenzo Moroni","doi":"10.1016/j.bbiosy.2021.100012","DOIUrl":"10.1016/j.bbiosy.2021.100012","url":null,"abstract":"<div><p>Recently, organ-on-a-chips (OoCs) have been proposed as highly innovative, truly predictive tools with limitless potential for organ function modelling, drug discovery and testing. By mimicking human key organ functions <em>in vitro</em>, they are proposed as models for studying physiological processes as well as disease-related mechanisms to elucidate pathological pathways and test the safety and efficacy of potential drug candidates, with unprecedented degree of physiological and clinical relevance. Despite the numerous efforts from biology and engineering, we expect that OoC will reach the next level by benefitting from high-tech technologies such as biofabrication, artificial intelligence (AI), robotics and automation.</p></div>","PeriodicalId":72379,"journal":{"name":"Biomaterials and biosystems","volume":"1 ","pages":"Article 100012"},"PeriodicalIF":0.0,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbiosy.2021.100012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9336326","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}
Dimitrios Tsiapalis , Stephen Kearns , Jack L. Kelly , Dimitrios I. Zeugolis
{"title":"Growth factor and macromolecular crowding supplementation in human tenocyte culture","authors":"Dimitrios Tsiapalis , Stephen Kearns , Jack L. Kelly , Dimitrios I. Zeugolis","doi":"10.1016/j.bbiosy.2021.100009","DOIUrl":"10.1016/j.bbiosy.2021.100009","url":null,"abstract":"<div><p>Cell-assembled tissue engineering strategies hold great potential in regenerative medicine, as three-dimensional tissue-like modules can be produced, even from a patient's own cells. However, the development of such implantable devices requires prolonged <em>in vitro</em> culture time, which is associated with cell phenotypic drift. Considering that the cells <em>in vivo</em> are subjected to numerous stimuli, multifactorial approaches are continuously gaining pace towards controlling cell fate during <em>in vitro</em> expansion. Herein, we assessed the synergistic effect of simultaneous and serial growth factor supplementation (insulin growth factor-1, platelet-derived growth factor <em>ββ,</em> growth differentiation factor 5 and transforming growth factor <em>β</em>3) to macromolecular crowding (carrageenan) in human tenocyte function; collagen synthesis and deposition; and gene expression. TGF<em>β</em>3 supplementation (without/with carrageenan) induced the highest (among all groups) DNA content. In all cases, tenocyte proliferation was significantly increased as a function of time in culture, whilst metabolic activity was not affected. Carrageenan supplementation induced significantly higher collagen deposition than groups without carrageenan (without/with any growth factor). Of all the growth factors used, TGF<em>β</em>3 induced the highest collagen deposition when used together with carrageenan in both simultaneous and serial fashion. At day 13, gene expression analysis revealed that TGF<em>β</em>3 in serial supplementation to carrageenan upregulated the most and downregulated the least collagen- and tendon- related genes and upregulated the least and downregulated the most osteo-, chondro-, fibrosis- and adipose- related trans-differentiation genes. Collectively, these data clearly advocate the beneficial effects of multifactorial approaches (in this case, growth factor and macromolecular crowding supplementation) in the development of functional cell-assembled tissue surrogates.</p></div>","PeriodicalId":72379,"journal":{"name":"Biomaterials and biosystems","volume":"1 ","pages":"Article 100009"},"PeriodicalIF":0.0,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbiosy.2021.100009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9336328","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}