Alessia Di Nubila , Meletios-Nikolaos Doulgkeroglou , Mehmet Gurdal , Stefanie H. Korntner , Dimitrios I. Zeugolis
{"title":"In vitro and in vivo assessment of a non-animal sourced chitosan scaffold loaded with xeno-free umbilical cord mesenchymal stromal cells cultured under macromolecular crowding conditions","authors":"Alessia Di Nubila , Meletios-Nikolaos Doulgkeroglou , Mehmet Gurdal , Stefanie H. Korntner , Dimitrios I. Zeugolis","doi":"10.1016/j.bbiosy.2024.100102","DOIUrl":"10.1016/j.bbiosy.2024.100102","url":null,"abstract":"<div><div>There is an increasing demand to not only accelerate the development of advanced therapy tissue engineered medicines, but to also eliminate xenogeneic materials from their development cycle. With these in mind, herein we first assessed the influence of carrageenan as macromolecular crowding agent to enhance and accelerate extracellular matrix deposition in xeno-free human umbilical cord mesenchymal stromal cell cultures and we developed and characterised a non-animal sourced chitosan scaffold. Following appropriate in vitro experimentation, a splinted nude mouse wound healing model was used to assess wound closure and scar size of non-treated control, non-animal sourced chitosan scaffold, non-animal sourced chitosan scaffold loaded with xeno-free human umbilical cord mesenchymal stromal cells and non-animal sourced chitosan scaffold loaded with xeno-free human umbilical cord mesenchymal stromal cells cultured under macromolecular crowding conditions groups. Across all three donors, carrageenan supplementation significantly increased collagen deposition at day 5, day 8 and day 11 without affecting cell morphology, viability, DNA concentration and metabolic activity. Through freeze drying, a non-animal sourced chitosan sponge was developed with appropriate structural and mechanical properties for wound healing applications. In vitro biological analysis made apparent that neither the scaffold nor macromolecular crowding negatively impacted xeno-free human umbilical cord mesenchymal stromal cell metabolic activity and proliferation. In vivo biological analysis revealed no significant differences between the groups in wound closure and scar size, raising question about the suitability of the model. In any case, this work sets the foundations for the development of completely xeno-free tissue engineered medicines.</div></div>","PeriodicalId":72379,"journal":{"name":"Biomaterials and biosystems","volume":"16 ","pages":"Article 100102"},"PeriodicalIF":0.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142432374","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":"Biomaterials functionalized with magnetic nanoparticles for tissue engineering: Between advantages and challenges","authors":"V. Goranov","doi":"10.1016/j.bbiosy.2024.100100","DOIUrl":"10.1016/j.bbiosy.2024.100100","url":null,"abstract":"<div><p>The integration of magnetic nanoparticles (MNPs) into biomaterials offers exciting opportunities for tissue engineering as they enable better control over cell guidance, release of bioactive factors and tissue maturation. Despite their potential, challenges such as the heterogeneity of MNPs, their cytotoxicity and the need for precise control of MNP`s properties hinder their widespread application. Overcoming these challenges will require new interdisciplinary efforts and technological advances, including the development of mathematical tools and additional elaborations to ensure the biocompatibility of MNPs.</p></div>","PeriodicalId":72379,"journal":{"name":"Biomaterials and biosystems","volume":"15 ","pages":"Article 100100"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666534424000138/pdfft?md5=e8e0a0af2e0a13268dd52d6ff3932c45&pid=1-s2.0-S2666534424000138-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142149551","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}
Zaid M. Younus , Ifty Ahmed , Paul Roach , Nicholas R. Forsyth
{"title":"A phosphate glass reinforced composite acrylamide gradient scaffold for osteochondral interface regeneration","authors":"Zaid M. Younus , Ifty Ahmed , Paul Roach , Nicholas R. Forsyth","doi":"10.1016/j.bbiosy.2024.100099","DOIUrl":"10.1016/j.bbiosy.2024.100099","url":null,"abstract":"<div><p>The bone-cartilage interface is defined by a unique arrangement of cells and tissue matrix. Injury to the interface can contribute to the development of arthritic joint disease. Attempts to repair osteochondral damage through clinical trials have generated mixed outcomes. Tissue engineering offers the potential of integrated scaffold design with multiregional architecture to assist in tissue regeneration, such as the bone-cartilage interface. Challenges remain in joining distinct materials in a single scaffold mass while maintaining integrity and avoiding delamination. The aim of the current work is to examine the possibility of joining two closely related acrylamide derivatives such as, poly n-isopropyl acrylamide (pNIPAM) and poly n‑tert‑butyl acrylamide (pNTBAM). The target is to produce a single scaffold unit with distinct architectural regions in the favour of regenerating the osteochondral interface. Longitudinal phosphate glass fibres (PGFs) with the formula 50P<sub>2</sub>O<sub>5</sub>.30CaO.20Na<sub>2</sub>O were incorporated to provide additional bioactivity by degradation to release ions such as calcium and phosphate which are considered valuable to assist the mineralization process. Polymers were prepared via atom transfer radical polymerization (ATRP) and solutions cast to ensure the integration of polymers chains. Scaffold was characterized using scanning electron microscope (SEM) and Fourier transform infra-red (FTIR) techniques. The PGF mass degradation pattern was inspected using micro computed tomography (µCT). Biological assessment of primary human osteoblasts (hOBs) and primary human chondrocytes (hCHs) upon scaffolds was performed using alizarin red and colorimetric calcium assay for mineralization assessment; alcian blue staining and dimethyl-methylene blue (DMMB) assay for glycosaminoglycans (GAGs); immunostaining and enzyme-linked immunosorbent assay (ELISA) to detect functional proteins expression by cells such as collagen I, II, and annexin A2. FTIR analysis revealed an intact unit with gradual transformation from pNIPAM to pNTBAM. SEM images showed three distinct architectural regions with mean pore diameter of 54.5 µm (pNIPAM), 16.5 µm (pNTBAM) and 118 µm at the mixed interface. Osteogenic and mineralization potential by cells was observed upon the entire scaffold's regions. Chondrogenic activity was relevant on the pNTBAM side of the scaffold only with minimal evidence in the pNIPAM region. PGFs increased mineralization potential of both hOBs and hCHs, evidenced by elevated collagens I, X, and annexin A2 with reduction of collagen II in PGFs scaffolds. In conclusion, pNIPAM and pNTBAM integration created a multiregional scaffold with distinct architectural regions. Differential chondrogenic, osteogenic, and mineralized cell performance, in addition to the impact of PGF, suggests a potential role for phosphate glass-incorporated, acrylamide-derivative scaffolds in osteochondral interface regeneration.</p></div>","PeriodicalId":72379,"journal":{"name":"Biomaterials and biosystems","volume":"15 ","pages":"Article 100099"},"PeriodicalIF":0.0,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666534424000126/pdfft?md5=013761879f791332fbc8262ad6ff339a&pid=1-s2.0-S2666534424000126-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141840695","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}
J. Frese , AP Schulz , B. Kowald , U.J. Gerlach , K.H. Frosch , R. Schoop
{"title":"Does the extent of bone defects affect the time to reach full weight-bearing after treatment with the Masquelet technique?","authors":"J. Frese , AP Schulz , B. Kowald , U.J. Gerlach , K.H. Frosch , R. Schoop","doi":"10.1016/j.bbiosy.2024.100098","DOIUrl":"10.1016/j.bbiosy.2024.100098","url":null,"abstract":"<div><h3>Methodology</h3><p>In a consecutive retrospective analysis of 190 patients treated with the Masquelet technique at the BG Klinikum Hamburg from January 2012 to January 2022, subgroup analysis for defect-specific features such as the extent and morphology of the defect were recorded, and their influence on the time to reach full weight-bearing of the affected limb was investigated.</p></div><div><h3>Results and conclusion</h3><p>A total of 217 defects were treated in 190 patients using the Masquelet technique. 70 % of all defects were in the tibia, followed by 22 % in the femur and only about 7 % in the upper extremity. The average length of all defects was 58 mm (+/- 31 mm), with the largest defect measuring 180 mm and the smallest measuring 20 mm. 89 % of the patients achieved full weight-bearing at the end of therapy. The average time from initiation of therapy to reaching safe full weight-bearing was 589 days. There was a significant correlation between defect length and time to reach full weight-bearing (<em>p</em> = 0.0134). These results could serve as a basis for creating a score for prognostics and evaluation of bone healing after treatment with the Masquelet technique. Additionally, the results could help guide indications for secondary stabilization using internal fixation.</p></div>","PeriodicalId":72379,"journal":{"name":"Biomaterials and biosystems","volume":"15 ","pages":"Article 100098"},"PeriodicalIF":0.0,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666534424000114/pdfft?md5=f1a313bc2ac6cefc2dc820cd03006840&pid=1-s2.0-S2666534424000114-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141622979","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}
Jaxson R. Libby , Haley Royce , Sarah R. Walker , Linqing Li
{"title":"The role of extracellular matrix in angiogenesis: Beyond adhesion and structure","authors":"Jaxson R. Libby , Haley Royce , Sarah R. Walker , Linqing Li","doi":"10.1016/j.bbiosy.2024.100097","DOIUrl":"10.1016/j.bbiosy.2024.100097","url":null,"abstract":"<div><p>While the extracellular matrix (ECM) has long been recognized for its structural contributions, anchoring cells for adhesion, providing mechanical support, and maintaining tissue integrity, recent efforts have elucidated its dynamic, reciprocal, and diverse properties on angiogenesis. The ECM modulates angiogenic signaling and mechanical transduction, influences the extent and degree of receptor activation, controls cellular behaviors, and serves as a reservoir for bioactive macromolecules. Collectively, these factors guide the formation, maturation, and stabilization of a functional vascular network. This review aims to shed light on the versatile roles of the ECM in angiogenesis, transcending its traditional functions as a mere structural material. We will explore its engagement and synergy in signaling modulation, interactions with various angiogenic factors, and highlight its importance in both health and disease. By capturing the essence of the ECM's diverse functionalities, we highlight the significance in the broader context of vascular biology, enabling the design of novel biomaterials to engineer vascularized tissues and their potential therapeutic implications.</p></div>","PeriodicalId":72379,"journal":{"name":"Biomaterials and biosystems","volume":"15 ","pages":"Article 100097"},"PeriodicalIF":0.0,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666534424000102/pdfft?md5=b40b78d2afdf15d3aabdb4d9e7113009&pid=1-s2.0-S2666534424000102-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141696440","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":"Discovering the nucleus in a world of biomaterials","authors":"Steven Vermeulen , Elizabeth Rosado Balmayor","doi":"10.1016/j.bbiosy.2024.100096","DOIUrl":"https://doi.org/10.1016/j.bbiosy.2024.100096","url":null,"abstract":"<div><p>The nucleus serves as the central hub for cellular activity, driving cell identity and behavior. Despite its crucial role, understanding how biomaterials influence the nucleus remains an underexplored area of research. In our opinion, this is an overlooked opportunity, particularly in regenerative medicine — a field where cellular control is not just beneficial, but essential. As such, we emphasize the need to recognize nuclear characteristics as a key metric for evaluating material functionality. In this leading opinion article, we discuss how state-of-the-art technologies can help reveal biomaterial-driven nuclear alterations, offering crucial insights that will advance the field of regenerative medicine.</p></div>","PeriodicalId":72379,"journal":{"name":"Biomaterials and biosystems","volume":"14 ","pages":"Article 100096"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666534424000096/pdfft?md5=6e94ca40eb3a32367ce139999d4386a9&pid=1-s2.0-S2666534424000096-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141323308","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}
Ksenia Menshikh , Ajay Kumar Reddy , Andrea Cochis , Francesca Fraulini , Alfonso Zambon , Gigliola Lusvardi , Lia Rimondini
{"title":"Bifunctional mesoporous glasses for bone tissue engineering: Biological effects of doping with cerium and polyphenols in 2D and 3D in vitro models","authors":"Ksenia Menshikh , Ajay Kumar Reddy , Andrea Cochis , Francesca Fraulini , Alfonso Zambon , Gigliola Lusvardi , Lia Rimondini","doi":"10.1016/j.bbiosy.2024.100095","DOIUrl":"https://doi.org/10.1016/j.bbiosy.2024.100095","url":null,"abstract":"<div><p>This study evaluates the cytocompatibility of cerium-doped mesoporous bioactive glasses (Ce-MBGs) loaded with polyphenols (Ce-MBGs-Poly) for possible application in bone tissue engineering after tumour resection. We tested MBGs powders and pellets on 2D and 3D <em>in vitro</em> models using human bone marrow-derived mesenchymal stem cells (hMSCs), osteosarcoma cells (U2OS), and endothelial cells (EA.hy926). Promisingly, at a low concentration in culture medium, Poly-loaded MBGs powders containing 1.2 mol% of cerium inhibited U2OS metabolic activity, preserved hMSCs viability, and had no adverse effects on EA.hy926 migration. Moreover, the study discussed the possible interaction between cerium and Poly, influencing anti-cancer effects. In summary, this research provides insights into the complex interactions between Ce-MBGs, Poly, and various cell types in distinct 2D and 3D <em>in vitro</em> models, highlighting the potential of loaded Ce-MBGs for post-resection bone tissue engineering with a balance between pro-regenerative and anti-tumorigenic activities.</p></div>","PeriodicalId":72379,"journal":{"name":"Biomaterials and biosystems","volume":"14 ","pages":"Article 100095"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666534424000084/pdfft?md5=e4422db84ca40304b9ae7f3184b665b2&pid=1-s2.0-S2666534424000084-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141289305","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}
N. Di Marzio , R. Tognato , E. Della Bella , V. De Giorgis , M. Manfredi , A. Cochis , M. Alini , T. Serra
{"title":"Differential proteomics profile of microcapillary networks in response to sound pattern-driven local cell density enhancement","authors":"N. Di Marzio , R. Tognato , E. Della Bella , V. De Giorgis , M. Manfredi , A. Cochis , M. Alini , T. Serra","doi":"10.1016/j.bbiosy.2024.100094","DOIUrl":"https://doi.org/10.1016/j.bbiosy.2024.100094","url":null,"abstract":"<div><p>Spatial cell organization and biofabrication of microcapillary networks in vitro has a great potential in tissue engineering and regenerative medicine. This study explores the impact of local cell density enhancement achieved through an innovative sound-based patterning on microcapillary networks formation and their proteomic profile. Human umbilical vein endothelial cells (HUVEC) and human pericytes from placenta (hPC-PL) were mixed in a fibrin suspension. The mild effect of sound-induced hydrodynamic forces condensed cells into architected geometries showing good fidelity to the numerical simulation of the physical process. Local cell density increased significantly within the patterned areas and the capillary-like structures formed following the cell density gradient. Over five days, these patterns were well-maintained, resulting in concentric circles and honeycomb-like structures.</p><p>Proteomic analysis of the pre-condensed cells cultured for 5 days, revealed over 900 differentially expressed proteins when cells were preassembled through mild-hydrodynamic forces. Gene ontology (GO) enrichment analysis identified cellular components, molecular functions, and biological processes that were up- and down-regulated, providing insights regarding molecular processes influenced by the local density enhancement. Furthermore, we employed Ingenuity Pathway Analysis (IPA) to identify altered pathways and predict upstream regulators. Notably, VEGF-A emerged as one of the most prominent upstream regulators.</p><p>Accordingly, this study initiates the unraveling of the changes in microcapillary networks at both molecular and proteins level induced by cell condensation obtained through sound patterning. The findings provide valuable insights for further investigation into sound patterning as a biofabrication technique for creating more complex microcapillary networks and advancing in vitro models.</p></div>","PeriodicalId":72379,"journal":{"name":"Biomaterials and biosystems","volume":"14 ","pages":"Article 100094"},"PeriodicalIF":0.0,"publicationDate":"2024-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666534424000072/pdfft?md5=b9e46a378471a23c07ff780cd8a03d9d&pid=1-s2.0-S2666534424000072-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140339009","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}
Mariia Lunova , Milan Jirsa , Alexandr Dejneka , Gareth John Sullivan , Oleg Lunov
{"title":"Mechanical regulation of mitochondrial morphodynamics in cancer cells by extracellular microenvironment","authors":"Mariia Lunova , Milan Jirsa , Alexandr Dejneka , Gareth John Sullivan , Oleg Lunov","doi":"10.1016/j.bbiosy.2024.100093","DOIUrl":"https://doi.org/10.1016/j.bbiosy.2024.100093","url":null,"abstract":"<div><p>Recently, it has been recognized that physical abnormalities (e.g. elevated solid stress, elevated interstitial fluid pressure, increased stiffness) are associated with tumor progression and development. Additionally, these mechanical forces originating from tumor cell environment through mechanotransduction pathways can affect metabolism. On the other hand, mitochondria are well-known as bioenergetic, biosynthetic, and signaling organelles crucial for sensing stress and facilitating cellular adaptation to the environment and physical stimuli. Disruptions in mitochondrial dynamics and function have been found to play a role in the initiation and advancement of cancer. Consequently, it is logical to hypothesize that mitochondria dynamics subjected to physical cues may play a pivotal role in mediating tumorigenesis. Recently mitochondrial biogenesis and turnover, fission and fusion dynamics was linked to mechanotransduction in cancer. However, how cancer cell mechanics and mitochondria functions are connected, still remain poorly understood. Here, we discuss recent studies that link mechanical stimuli exerted by the tumor cell environment and mitochondria dynamics and functions. This interplay between mechanics and mitochondria functions may shed light on how mitochondria regulate tumorigenesis.</p></div>","PeriodicalId":72379,"journal":{"name":"Biomaterials and biosystems","volume":"14 ","pages":"Article 100093"},"PeriodicalIF":0.0,"publicationDate":"2024-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666534424000060/pdfft?md5=d39fd2e0f78678b7a5eb9f616ab7467f&pid=1-s2.0-S2666534424000060-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140321301","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 role of inflammatory mediators and matrix metalloproteinases (MMPs) in the progression of osteoarthritis","authors":"Anwesha Mukherjee, Bodhisatwa Das","doi":"10.1016/j.bbiosy.2024.100090","DOIUrl":"https://doi.org/10.1016/j.bbiosy.2024.100090","url":null,"abstract":"<div><p>Osteoarthritis (OA) is a chronic musculoskeletal disorder characterized by an imbalance between (synthesis) and catabolism (degradation) in altered homeostasis of articular cartilage mediated primarily by the innate immune system. OA degenerates the joints resulting in synovial hyperplasia, degradation of articular cartilage with damage of the structural and functional integrity of the cartilage extracellular matrix, subchondral sclerosis, osteophyte formation, and is characterized by chronic pain, stiffness, and loss of function. Inflammation triggered by factors like biomechanical stress is involved in the development of osteoarthritis. In OA apart from catabolic effects, anti-inflammatory anabolic processes also occur continually. There is also an underlying chronic inflammation present, not only in cartilage tissue but also within the synovium, which perpetuates tissue destruction of the OA joint. The consideration of inflammation in OA considers synovitis and/or other cellular and molecular events in the synovium during the progression of OA. In this review, we have presented the progression of joint degradation that results in OA. The critical role of inflammation in the pathogenesis of OA is discussed in detail along with the dysregulation within the cytokine networks composed of inflammatory and anti-inflammatory cytokines that drive catabolic pathways, inhibit matrix synthesis, and promote cellular apoptosis. OA pathogenesis, fluctuation of synovitis, and its clinical impact on disease progression are presented here along with the role of synovial macrophages in promoting inflammatory and destructive responses in OA. The role of interplay between different cytokines, structure, and function of their receptors in the inter-cellular signaling pathway is further explored. The effect of cytokines in the increased synthesis and release of matrix-decomposing proteolytic enzymes, such as matrix metalloproteinase (MMPs) and a disintegrin-like and metalloproteinase with thrombospondin motif (ADAMTS), is elaborated emphasizing the potential impact of MMPs on the chondrocytes, synovial cells, articular and periarticular tissues, and other immune system cells migrating to the site of inflammation. We also shed light on the pathogenesis of OA via oxidative damage particularly due to nitric oxide (NO) via its angiogenic response to inflammation. We concluded by presenting the current knowledge about the tissue inhibitors of metalloproteinases (TIMPs). Synthetic MMP inhibitors include zinc binding group (ZBG), non-ZBG, and mechanism-based inhibitors, all of which have the potential to be therapeutically beneficial in the treatment of osteoarthritis. Improving our understanding of the signaling pathways and molecular mechanisms that regulate the MMP gene expression, may open up new avenues for the creation of therapies that can stop the joint damage associated with OA.</p></div>","PeriodicalId":72379,"journal":{"name":"Biomaterials and biosystems","volume":"13 ","pages":"Article 100090"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666534424000035/pdfft?md5=c37f6194ffd0bc0e6eab89940301458b&pid=1-s2.0-S2666534424000035-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139993201","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}