Anders Runge Walther , Nicholas Ditzel , Moustapha Kassem , Morten Østergaard Andersen , Martin Aage Barsøe Hedegaard
{"title":"In vivo non-invasive monitoring of tissue development in 3D printed subcutaneous bone scaffolds using fibre-optic Raman spectroscopy","authors":"Anders Runge Walther , Nicholas Ditzel , Moustapha Kassem , Morten Østergaard Andersen , Martin Aage Barsøe Hedegaard","doi":"10.1016/j.bbiosy.2022.100059","DOIUrl":"10.1016/j.bbiosy.2022.100059","url":null,"abstract":"<div><p>The development of novel biomaterials for regenerative therapy relies on the ability to assess tissue development, quality, and similarity with native tissue types in <em>in vivo</em> experiments. Non-invasive imaging modalities such as X-ray computed tomography offer high spatial resolution but limited biochemical information while histology and biochemical assays are destructive. Raman spectroscopy is a non-invasive, label-free and non-destructive technique widely applied for biochemical characterization. Here we demonstrate the use of fibre-optic Raman spectroscopy for <em>in vivo</em> quantitative monitoring of tissue development in subcutaneous calcium phosphate scaffolds in mice over 16 weeks. Raman spectroscopy was able to quantify the time dependency of different tissue components related to the presence, absence, and quantity of mesenchymal stem cells. Scaffolds seeded with stem cells produced 3–5 times higher amount of collagen-rich extracellular matrix after 16 weeks implantation compared to scaffolds without. These however, showed a 2.5 times higher amount of lipid-rich tissue compared to implants with stem cells. <em>Ex vivo</em> micro-computed tomography and histology showed stem cell mediated collagen and bone development. Histological measures of collagen correlated well with Raman derived quantifications (correlation coefficient <em>in vivo</em> 0.74, <em>ex vivo</em> 0.93). In the absence of stem cells, the scaffolds were largely occupied by adipocytes. The technique developed here could potentially be adapted for a range of small animal experiments for assessing tissue engineering strategies at the biochemical level.</p></div>","PeriodicalId":72379,"journal":{"name":"Biomaterials and biosystems","volume":"7 ","pages":"Article 100059"},"PeriodicalIF":0.0,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/4e/60/main.PMC9934492.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10774018","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}
Zehong Xiang , Xinghua Guan , Zhifang Ma , Qiang Shi , Mikhail Panteleev , Fazly I. Ataullakhanov
{"title":"Bioactive engineered scaffolds based on PCL-PEG-PCL and tumor cell-derived exosomes to minimize the foreign body reaction","authors":"Zehong Xiang , Xinghua Guan , Zhifang Ma , Qiang Shi , Mikhail Panteleev , Fazly I. Ataullakhanov","doi":"10.1016/j.bbiosy.2022.100055","DOIUrl":"10.1016/j.bbiosy.2022.100055","url":null,"abstract":"<div><p>Long-term presence of M1 macrophages causes serious foreign body reaction (FBR), which is the main reason for the failure of biological scaffold integration. Inducing M2 polarization of macrophages near scaffolds to reduce foreign body response has been widely researched. In this work, inspired by the special capability of tumor exosomes in macrophages M2 polarization, we integrate tumor-derived exosomes into biological scaffolds to minimize the FBR. In brief, breast cancer cell-derived exosomes are loaded into polycaprolactone-b-polyethylene glycol-b-polycaprolactone (PCL-PEG-PCL) fiber scaffold through physical adsorption and entrapment to constructed bioactive engineered scaffold. In cellular experiments, we demonstrate bioactive engineered scaffold based on PCL-PEG-PCL and exosomes can promote the transformation of macrophages from M1 to M2 through the PI3K/Akt signaling pathway. In addition, the exosomes release gradually from scaffolds and act on the macrophages around the scaffolds to reduce FBR in a subcutaneous implant mouse model. Compared with PCL-PEG-PCL scaffolds without exosomes, bioactive engineered scaffolds reduce significantly inflammation and fibrosis of tissues around the scaffolds. Therefore, cancer cell-derived exosomes show the potential for constructing engineered scaffolds in inhibiting the excessive inflammation and facilitating tissue formation.</p></div>","PeriodicalId":72379,"journal":{"name":"Biomaterials and biosystems","volume":"7 ","pages":"Article 100055"},"PeriodicalIF":0.0,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/8d/6c/main.PMC9934494.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10762305","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}
Marie P.F. Corradi , Alyanne M. de Haan , Bernard Staumont , Aldert H. Piersma , Liesbet Geris , Raymond H.H. Pieters , Cyrille A.M. Krul , Marc A.T. Teunis
{"title":"Natural language processing in toxicology: Delineating adverse outcome pathways and guiding the application of new approach methodologies","authors":"Marie P.F. Corradi , Alyanne M. de Haan , Bernard Staumont , Aldert H. Piersma , Liesbet Geris , Raymond H.H. Pieters , Cyrille A.M. Krul , Marc A.T. Teunis","doi":"10.1016/j.bbiosy.2022.100061","DOIUrl":"10.1016/j.bbiosy.2022.100061","url":null,"abstract":"<div><p>Adverse Outcome Pathways (AOPs) are conceptual frameworks that tie an initial perturbation (molecular initiating event) to a phenotypic toxicological manifestation (adverse outcome), through a series of steps (key events). They provide therefore a standardized way to map and organize toxicological mechanistic information. As such, AOPs inform on key events underlying toxicity, thus supporting the development of New Approach Methodologies (NAMs), which aim to reduce the use of animal testing for toxicology purposes.</p><p>However, the establishment of a novel AOP relies on the gathering of multiple streams of evidence and information, from available literature to knowledge databases. Often, this information is in the form of free text, also called unstructured text, which is not immediately digestible by a computer. This information is thus both tedious and increasingly time-consuming to process manually with the growing volume of data available. The advancement of machine learning provides alternative solutions to this challenge. To extract and organize information from relevant sources, it seems valuable to employ deep learning Natural Language Processing techniques.</p><p>We review here some of the recent progress in the NLP field, and show how these techniques have already demonstrated value in the biomedical and toxicology areas. We also propose an approach to efficiently and reliably extract and combine relevant toxicological information from text. This data can be used to map underlying mechanisms that lead to toxicological effects and start building quantitative models, in particular AOPs, ultimately allowing animal-free human-based hazard and risk assessment.</p></div>","PeriodicalId":72379,"journal":{"name":"Biomaterials and biosystems","volume":"7 ","pages":"Article 100061"},"PeriodicalIF":0.0,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9934466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10762307","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":"Developing a clinical grade human adipose decellularized biomaterial","authors":"Daniel J. Hayes , Jeffrey M Gimble","doi":"10.1016/j.bbiosy.2022.100053","DOIUrl":"10.1016/j.bbiosy.2022.100053","url":null,"abstract":"<div><p>While tissue engineering investigators have appreciated adipose tissue as a repository of stromal/stem cells, they are only now beginning to see its value as a decellularized tissue resource. Independent academic investigators have successfully extracted lipid, genomic DNA and proteins from human fat to create a decellularized extracellular matrix enriched in collagen, glycoproteins, and proteoglycans. Pre-clinical studies have validated its compatibility with stromal/stem cells and its ability to support adipogenesis <em>in vitro</em> and <em>in vivo</em> in both small (murine) and large (porcine) subcutaneous implant models. Furthermore, Phase I safety clinical trials have injected decellularized human adipose tissue scaffolds in human volunteers without incident for periods of up to 127 days. This commentary takes an opinionated look at the under-appreciated but potential benefits of obesity as an increasingly available biomaterial resource.</p></div>","PeriodicalId":72379,"journal":{"name":"Biomaterials and biosystems","volume":"7 ","pages":"Article 100053"},"PeriodicalIF":0.0,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6d/2c/main.PMC9934471.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10762302","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}
Ekaterina Smotrova, Simin Li, Vadim V. Silberschmidt
{"title":"Mechanoregulated trabecular bone adaptation: Progress report on in silico approaches","authors":"Ekaterina Smotrova, Simin Li, Vadim V. Silberschmidt","doi":"10.1016/j.bbiosy.2022.100058","DOIUrl":"https://doi.org/10.1016/j.bbiosy.2022.100058","url":null,"abstract":"<div><p><em>Adaptation</em> is the process by which bone responds to changes in loading environment and modulates its properties and spatial organization to meet the mechanical demands. Adaptation in trabecular bone is achieved through increase in bone mass and alignment of trabecular-bone morphology along the loading direction. This transformation of internal microstructure is governed by mechanical stimuli sensed by mechanosensory cells in the bone matrix. Realisation of adaptation in the form of local bone-resorption and -formation activities as a function of mechanical stimuli is still debated. <em>In silico</em> modelling is a useful tool for simulation of various scenarios that cannot be investigated <em>in vivo</em> and particularly well suited for prediction of trabecular bone adaptation. This progress report presents the recent advances in <em>in silico</em> modelling of mechanoregulated adaptation at the scale of trabecular bone tissue. Four well-established bone-adaptation models are reviewed in terms of their recent improvements and validation. They consider various mechanical factors: (i) strain energy density, (ii) strain and damage, (iii) stress nonuniformity and (iv) daily stress. Contradictions of these models are discussed and their ability to describe adequately a real-life mechanoregulation process in bone is compared.</p></div>","PeriodicalId":72379,"journal":{"name":"Biomaterials and biosystems","volume":"7 ","pages":"Article 100058"},"PeriodicalIF":0.0,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666534422000204/pdfft?md5=1414a6bd202e29c844a5774b6c4c5b2e&pid=1-s2.0-S2666534422000204-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91957678","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}
Samineh Barmaki , Ahmed Al-Samadi , Katarzyna Leskinen , Wafa Wahbi , Ville Jokinen , Sanna Vuoristo , Tuula Salo , Juha Kere , Satu Wedenoja , Päivi Saavalainen
{"title":"Transcriptomic Profiling of JEG-3 cells using human leiomyoma derived matrix","authors":"Samineh Barmaki , Ahmed Al-Samadi , Katarzyna Leskinen , Wafa Wahbi , Ville Jokinen , Sanna Vuoristo , Tuula Salo , Juha Kere , Satu Wedenoja , Päivi Saavalainen","doi":"10.1016/j.bbiosy.2022.100056","DOIUrl":"10.1016/j.bbiosy.2022.100056","url":null,"abstract":"<div><p>Oxygen tension varies during placental and fetal development. Although hypoxia drives early trophoblast invasion, low placental oxygen levels during pregnancy show association with pregnancy complications including fetal growth restriction and preeclampsia. JEG-3 cells are often used as a trophoblast model. We studied transcriptional changes of JEG-3 cells on a uterine leiomyoma derived matrix Myogel. This might be the closest condition to the real uterine environment that we can get for an in vitro model. We observed that culturing JEG-3 cells on the leiomyoma matrix leads to strong stimulation of ribosomal pathways, energy metabolism, and ATP production. Furthermore, Myogel improved JEG-3 cell adherence in comparison to tissue culture treated plastic. We also included PDMS microchip hypoxia creation, and observed changes in oxidative phosphorylation, oxygen related genes and several hypoxia genes. Our study highlights the effects of Myogel matrix on growing JEG-3 cells, especially on mitochondria, energy metabolism, and protein synthesis.</p></div>","PeriodicalId":72379,"journal":{"name":"Biomaterials and biosystems","volume":"7 ","pages":"Article 100056"},"PeriodicalIF":0.0,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9934486/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10774017","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}
A.G. Ibrahim , A. Ciullo , C. Li , G. Garcia , K. Peck , K. Miyamoto , V. Arumugaswami , E. Marbán
{"title":"Engineered extracellular vesicles antagonize SARS-CoV-2 infection by inhibiting mTOR signaling","authors":"A.G. Ibrahim , A. Ciullo , C. Li , G. Garcia , K. Peck , K. Miyamoto , V. Arumugaswami , E. Marbán","doi":"10.1016/j.bbiosy.2022.100042","DOIUrl":"10.1016/j.bbiosy.2022.100042","url":null,"abstract":"<div><p>Effective treatment approaches for patients with COVID-19 remain limited and are neither curative nor widely applicable. Activated specialized tissue effector extracellular vesicles (ASTEX) derived from genetically-enhanced skin fibroblasts, exert disease-modifying bioactivity <em>in vivo</em> in models of heart and lung injury. Here we report that ASTEX antagonizes SARS-CoV-2 infection and its pathogenic sequelae. In human lung epithelial cells exposed to SARS-CoV-2, ASTEX is cytoprotective and antiviral. Transcriptomic analysis implicated the mammalian target of rapamycin (mTOR) pathway, as infected cells upregulated mTOR signaling and pre-exposure to ASTEX attenuated it. The implication of mTOR signaling was further confirmed using mTOR inhibition and activation, which increased and decreased viral load, respectively. Dissection of ASTEX cargo identifies miRs including miR-16 as potential inhibitors of mTOR signaling. The findings reveal a novel, dual mechanism of action for ASTEX as a therapeutic candidate for COVID-19, with synergistic antiviral and cytoprotective benefits.</p></div>","PeriodicalId":72379,"journal":{"name":"Biomaterials and biosystems","volume":"6 ","pages":"Article 100042"},"PeriodicalIF":0.0,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/4a/de/main.PMC8841010.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9307851","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}
Elizabeth Sainsbury , Ronaldo do Amaral , Alexander W. Blayney , Rory McConn Walsh , Fergal J. O'Brien , Cian O'Leary
{"title":"Tissue engineering and regenerative medicine strategies for the repair of tympanic membrane perforations","authors":"Elizabeth Sainsbury , Ronaldo do Amaral , Alexander W. Blayney , Rory McConn Walsh , Fergal J. O'Brien , Cian O'Leary","doi":"10.1016/j.bbiosy.2022.100046","DOIUrl":"10.1016/j.bbiosy.2022.100046","url":null,"abstract":"<div><p>Despite the high success rate of autologous grafts in tympanic membrane repair, clinical alternatives are required for the closure of unresponsive chronic perforations that can lead to recurring infection and hearing loss. Tissue engineering and regenerative medicine approaches have emerged as another strategy to repair the eardrum, in addition to negating the need for donor tissue harvest and related surgical iatrogenicities. This review highlights the main approaches using biomaterials, growth factors, and cell therapies towards the healing of complex TM perforations. In addition, we discuss the challenges and advances for the development of reliable animal models, which will allow the optimisation and development of novel techniques. Finally, we indicate technologies that are currently used clinically and others that are closer to the market. The advances here discussed on tissue engineering and regenerative medicine strategies applied to the field of TM perforations will allow otologists, surgeons, and researchers to better bring novel technologies to the bedside as well as to develop new ones.</p></div>","PeriodicalId":72379,"journal":{"name":"Biomaterials and biosystems","volume":"6 ","pages":"Article 100046"},"PeriodicalIF":0.0,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/4f/59/main.PMC9934438.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9321495","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}
Jeremy A. Antonyshyn , Meghan J. McFadden , Anthony O. Gramolini , Stefan O.P. Hofer , J. Paul Santerre
{"title":"Vascular tissue engineering from human adipose tissue: fundamental phenotype of its resident microvascular endothelial cells and stromal/stem cells","authors":"Jeremy A. Antonyshyn , Meghan J. McFadden , Anthony O. Gramolini , Stefan O.P. Hofer , J. Paul Santerre","doi":"10.1016/j.bbiosy.2022.100049","DOIUrl":"10.1016/j.bbiosy.2022.100049","url":null,"abstract":"<div><p>Adipose tissue is an abundant, accessible, and uniquely dispensable source of cells for vascular tissue engineering. Despite its intrinsic endothelial cells, considerable effort is directed at deriving endothelium from its resident stem and progenitor cells. Here, we investigate the composition of human adipose tissue and characterize the phenotypes of its constituent cells in order to help ascertain their potential utility for vascular tissue engineering. Unsupervised clustering based on cell-surface protein signatures failed to detect CD45<sup>–</sup>CD31<sup>–</sup>VEGFR2<sup>+</sup> endothelial progenitor cells within adipose tissue, but supported further investigation of its resident CD45<sup>–</sup>CD31<sup>+</sup> microvascular endothelial cells (HAMVECs) and CD45<sup>–</sup>CD31<sup>–</sup> stromal/stem cells (ASCs). The endothelial differentiation of ASCs altered their proteome, but it remained distinct from that of primary endothelial cell controls – as well as HAMVECs – regardless of their arterial-venous specification or macrovascular-microvascular origin. Rather, ASCs retained a proteome indicative of a perivascular phenotype, which was supported by their ability to facilitate the capillary morphogenesis of HAMVECs. This study supports the use of HAMVECs for the generation of endothelium. It suggests that the utility of ASCs for vascular tissue engineering lies in their capacity to remodel the extracellular matrix and to function as mural cells.</p></div>","PeriodicalId":72379,"journal":{"name":"Biomaterials and biosystems","volume":"6 ","pages":"Article 100049"},"PeriodicalIF":0.0,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/26/a3/main.PMC9934493.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10830853","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}