Biomaterials and biosystems最新文献

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.

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.

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 in vitro 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 in vitro models, highlighting the potential of loaded Ce-MBGs for post-resection bone tissue engineering with a balance between pro-regenerative and anti-tumorigenic activities.

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.

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.

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.

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.

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.

This review highlights the importance of extracellular matrix (ECM) biomaterials in understanding the biology of human trabecular meshwork (TM) and Schlemm's canal (SC) cells under normal and simulated glaucoma-like conditions. We provide an overview of recent progress in the development and application of state-of-the-art 3D ECM biomaterials including cell-derived ECM, ECM scaffolds, Matrigel, and ECM hydrogels for studies of TM and SC cell (patho)biology. Such bioengineered platforms enable accurate and reliable modeling of tissue-like cell-cell and cell-ECM interactions. They bridge the gap between conventional 2D approaches and in vivo/ex vivo models, and have the potential to aid in the identification of the causal mechanism(s) for outflow dysfunction in ocular hypertensive glaucoma. We discuss each model's benefits and limitations, and close with an outlook on future directions.

Novel cartilage regeneration therapies often look promising in-vitro but fail when implanted in vivo. One of the possible reasons for this discrepancy is the simplified, static in-vitro chondrogenesis models typically used. Complex mechanical stimulation plays a key role in physiological cartilage and chondrogenic cell metabolism, including the development of cartilage structure, yet it is routinely lacking during in-vitro studies. Multiaxial load bioreactors are becoming more widespread and offer advantages over more simple loading devices. Within this article, we highlight some of the important findings from in-vitro assays and key aspects relating to tribological loading of cartilage and chondrogenic cells.

Biomaterials that can improve the healing of articular cartilage lesions are needed. To address this unmet need, we developed novel 3D printed silica/poly(tetrahydrofuran)/poly(ε-caprolactone) (SiO₂/PTHF/PCL-diCOOH) hybrid scaffolds. Our aim was to carry out essential studies to advance this medical device towards functional validation in pre-clinical trials. First, we show that the chemical composition, microarchitecture and mechanical properties of these scaffolds were not affected by sterilisation with gamma irradiation. To evaluate the systemic and local immunogenic reactivity of the sterilised 3D printed hybrid scaffolds, they were implanted subcutaneously into Balb/c mice. The scaffolds did not trigger a systemic inflammatory response over one week of implantation. The interaction between the host immune system and the implanted scaffold elicited a local physiological reaction with infiltration of mononuclear cells without any signs of a chronic inflammatory response.

Then, we investigated how these 3D printed hybrid scaffolds direct chondrogenesis in vitro. Human bone marrow-derived mesenchymal stem/stromal cells (hBM-MSCs) seeded within the 3D printed hybrid scaffolds were cultured under normoxic or hypoxic conditions, with or without chondrogenic supplements. Chondrogenic differentiation assessed by both gene expression and protein production analyses showed that 3D printed hybrid scaffolds support hBM-MSC chondrogenesis. Articular cartilage-specific extracellular matrix deposition within these scaffolds was enhanced under hypoxic conditions (1.7 or 3.7 fold increase in the median of aggrecan production in basal or chondrogenic differentiation media).

Our findings show that 3D printed SiO₂/PTHF/PCL-diCOOH hybrid scaffolds have the potential to support the regeneration of cartilage tissue.

The fabrication of customized implants by additive manufacturing has allowed continued development of the personalized medicine field. Herein, a 3D-printed bioabsorbable poly (lactic acid) (PLA)- β-tricalcium phosphate (TCP) (10 wt %) composite has been modified with CeO₂ nanoparticles (CeNPs) (1, 5 and 10 wt %) for bone repair. The filaments were prepared by melt extrusion and used to print porous scaffolds. The nanocomposite scaffolds possessed precise structure with fine print resolution, a homogenous distribution of TCP and CeNP components, and mechanical properties appropriate for bone tissue engineering applications. Cell proliferation assays using osteoblast cultures confirmed the cytocompatibility of the composites. In addition, the presence of CeNPs enhanced the proliferation and differentiation of mesenchymal stem cells; thereby, increasing alkaline phosphatase (ALP) activity, calcium deposition and bone-related gene expression. Results from this study have shown that the 3D printed PLA-TCP-10%CeO₂ composite scaffold could be used as an alternative polymeric implant for bone tissue engineering applications: avoiding additional/revision surgeries and accelerating the regenerative process.