Search Results (334)

Background and Objectives: Posterior chamber phakic implantable contact lenses (Phakic-ICL) are widely used for refractive correction due to their efficacy and safety, including minimal corneal endothelial cell loss. The Collamer-based EVO+ Visian implantable contact lens (ICL), manufactured from Collamer, which is a blend of collagen and hydroxyethyl methacrylate (HEMA), has demonstrated excellent long-term biocompatibility and optical clarity. Recently, hydrophilic acrylic Phakic-ICLs, such as the Implantable Phakic Contact Lens (IPCL), have been introduced. This study investigated the material differences among Phakic-ICLs and their interaction with fibronectin (FN), which has been reported to adhere to intraocular lens (IOL) surfaces following implantation. The aim was to compare Collamer, IPCL, and LENTIS lenses (used as control) in terms of FN distribution and cell adhesion using a small number of explanted Phakic-ICLs. Materials and Methods: Three lens types were analyzed: a Collamer Phakic-ICL (EVO+ Visian ICL), a hydrophilic acrylic IPCL, and a hydrophilic acrylic phakic-IOL (LENTIS). FN distribution and cell adhesion were evaluated across different regions of each lens. An in vitro FN-coating experiment was conducted to assess its effect on cell adhesion. Results: All lenses demonstrated minimal FN deposition and cellular adhesion in the central optical zone. A thin FN film was observed on the haptics of Collamer lenses, while FN adhesion was weaker or absent on IPCL and LENTIS surfaces. Following FN coating, Collamer lenses supported more uniform FN film formation; however, this did not significantly enhance cell adhesion. Conclusions: Collamer, which contains collagen, promotes FN film formation. Although FN film formation was enhanced, the low cell-adhesive properties of HEMA resulted in minimal cell adhesion even with FN presence. This characteristic may contribute to the long-term transparency and biocompatibility observed clinically. In contrast, hydrophilic acrylic materials used in IPCL and LENTIS demonstrated limited FN interaction. These material differences may influence extracellular matrix protein deposition and biocompatibility in clinical settings, warranting further investigation. Full article

Age-related macular degeneration (AMD) is the main cause of blindness in Western nations. AMD models addressing specific pathological pathways are desired. Through this study, a best-practice protocol for polarized porcine single-eye retinal pigment epithelium (RPE) preparation for AMD-relevant models of RPE barrier and polarity is established. Single-eye porcine primary RPE cells (from one eye for one well) were prepared in 12-well plates including Transwell inserts. Different coatings (laminin (Lam), Poly-ᴅ-Lysine (PDL), fibronectin (Fn) and collagens) and varying serum contents (1%, 5% and 10%) were investigated to determine optimal culture parameters for this model. Success rates of cultures, cell number (trypan-blue exclusion assay), morphology/morphometry (light and fluorescence microscopy), protein secretion/expression (ELISA, Western blot), gene expression (qPCR), transepithelial electric resistance (TEER) and polar location of bestrophin 1 (BEST1) by cryosectioning (IHC-Fr) were assessed. Cells seeded on Lam exhibited the highest level of epithelial cells and confluence properties. Fn resulted in the highest cell number growth. Lam and Fn exhibited the highest culture success rates. TEER values and vascular endothelial growth factor secretion were highest when Lam was used. For the first time, polar (Transwell) porcine single-eye RPE morphometry parameters were determined. RPE on Lam showed bigger cells with a higher variety of cell shapes. CIV displayed the lowest claudin 19 expression. The highest basolateral expression of BEST1 was achieved with Lam coating. The higher the serum, the better the cell number increase and confluence success. A reduction in serum on Lam showed positive results for RPE morphology, while morphometry remained stable. A five percent serum on Lam showed the highest culture success rate and best barrier properties. RPE65 expression was reduced by using 10% serum. Altogether, the most suitable coating of Transwell inserts was Lam, and a reduction in serum to 5% is recommended, as well as a cultivation time of 28 days. A protocol for the use of polar porcine single-eye cultures with validated parameters was established and is provided herein. Full article

Both biochemical cues and the electrophysiological microenvironment play a pivotal role in influencing cell behaviors. In this study, collagen/polypyrrole biomimetic electroactive composite coatings with a fiber network structure were constructed on the surface of titanium substrates by hot alkali treatment and stepwise electrochemical deposition. Materialistic characterization and electrochemical performance tests demonstrated that the titanium electrodes modified with collagen/polypyrrole composite coatings exhibited the surface morphology of a collagen film layer, and their electroactivity was significantly enhanced. Cellular experiments demonstrated that the collagen in the composite coatings could provide good biomimetic biochemical cues as a main extracellular matrix component, which have a substantial effect in promoting cell adhesion, proliferation, and osteogenic differentiation. Furthermore, under exogenous electrical signals, the polypyrrole coating has the capacity to facilitate an appropriate electrophysiological microenvironment, thereby promoting osteogenic differentiation. The collagen/polypyrrole composite coating exhibited a better effect in promoting osteogenic differentiation among all samples by simultaneously providing the appropriate biochemical cues and electrophysiological microenvironments. This work demonstrates the feasibility of synergistic pro-osteogenesis by biochemical cues and an electrophysiological microenvironment, which is instructive for the field of bone tissue engineering. Full article

Due to the limited regeneration of cartilage, new implant materials are needed. Biodegradable polymers poly-(D,L)-lactide-ε-caprolactone-methacrylate (LCM) and polyamid-ε-caprolactone-methacrylate (ACM) were recently established and coated with heparin, making them able to prevent blood coagulation and cartilage mineralization. The aim of this study was to analyze the suitability of LCM and ACM alone or coated with heparin (the latter are abbreviated as LCMH and ACMH, respectively) as implant material for cartilage repair. Therefore, mesenchymal stem cells were chondrogenically differentiated in 2D cultures with polymer discs. Differentiation was induced by the supplementation of cell medium with dimethyloxalylglycine, TGF-β, and BMP2. After 5 days, no increase in proinflammatory factors was observed. Cell viability declined on ACM and ACMH discs. During early chondrogenesis, SOX9 expression increased on LCM and LCMH discs, while TRPV4 expression decreased on ACMH discs. At day 20, the level of collagen type II increased on LCM, LCMH, and ACM discs, demonstrating the ability of chondrogenic development on these implants. In summary, coating with heparin showed no advantages compared to pure LCM and ACM. For cartilage repair, LCM is more suitable than ACM in this 2D in vitro model, which needs to be verified by long-term 3D models and in vivo studies. Full article

To address the dual clinical challenges of poor osseointegration and inadequate analgesia caused by postoperative infections in traditional titanium implants, this study proposes a multifunctional synergistic strategy based on metal—organic frameworks (MOFs). By integrating drug-controlled release and ionic microenvironment regulation, it constructs a titanium-based implant coating system with antibacterial and bone-regenerative properties. Ketoprofen, a drug with excellent analgesic properties, was loaded into MgCu-MOF74 powder, and the Ket@MgCu-MOF74 powder was successfully anchored onto the surface of the titanium alloy through dopamine-mediated adhesion. The maximum load of ketoprofen to MgCu-MOF74 is 18.55%, and it has a good controllable release effect. The results showed that MgCu-MOF74/Ti and Ket@MgCu-MOF74/Ti coatings enhanced osteogenic performance by promoting alkaline phosphatase activity, collagen secretion, and extracellular matrix mineralization. Additionally, the release of Mg²⁺ and Cu²⁺ created an alkaline environment, providing antibacterial properties. In summary, the MOF enabled the controlled release of ketoprofen, and the composite coating can improve osteogenic differentiation of osteoblasts and enhance the antibacterial properties of titanium alloy implants. Full article

Background: Resorbable biopolymers are increasingly explored for use in regenerative procedures within dental surgery. Their ability to degrade naturally, minimize surgical reinterventions, and potentially reduce immunogenicity makes them appealing in guided bone and tissue regeneration applications. However, despite these advantages, uncertainties persist regarding their comparative effectiveness and associated risks. For example, polyethylene glycol (PEG)-based membranes have shown comparable outcomes to porcine-derived collagen membranes in bone regeneration procedures, yet studies have reported a higher incidence of soft tissue healing complications associated with PEG-based materials. Similarly, while polycaprolactone (PCL) and dextrin-based hydrogels have demonstrated promising clinical handling and bone fill capabilities, their long-term performance and consistency across different anatomical sites remain under investigation. These findings highlight the need for further well-powered clinical trials to establish standardized guidelines for their safe and effective use. Methods: A systematic review protocol was registered with the PROSPERO database and developed in alignment with PRISMA guidelines. Database searches were conducted in PubMed, Medline, Scopus, and Cochrane from June to December 2024. Only randomized controlled trials (RCTs) focusing on synthetic resorbable biopolymers in bone augmentation procedures were considered. Bias was evaluated using the Cochrane Risk of Bias tool. Results: Eleven RCTs were included, totaling 188 patients. The findings suggest that materials such as polylactic acid (PLA), polycaprolactone (PCL), and polyethylene glycol (PEG) contributed effectively to new bone formation. PEG-based membranes were found to perform on par with or occasionally better than traditional collagen membranes derived from porcine sources. Additionally, the application of 3D-printable polymers demonstrated promise in site-specific healing. Conclusions: Resorbable biopolymers are effective and safe for GBR procedures, with clinical outcomes comparable to traditional materials. Advances in 3D-printing technology and bioactive coatings may further enhance their regenerative potential. However, the incidence of soft tissue healing complications suggests the need for further long-term studies to optimize material properties and clinical application. Full article

Background: Endothelial dysfunction triggers atherosclerosis pathogenesis. This study aimed at developing a 3D scaffold model able to reproduce in vitro the human vascular intima and study the endothelial damage induced by oxidative low-density lipoproteins (ox-LDLs) and shear stress. (2) Methods: Three-dimensional sandwich-like scaffolds were fabricated using electrospinning technology, functionalized with type I collagen and laminin, and subsequently coated with methacrylated gelatin hydrogel (GelMa) to achieve the final composite structure. Human umbilical vein endothelial cells (HUVECs) were used as the cell model for testing the suitability of 3D supports for cell culture exposed to ox-LDL both under static and shear stress conditions. Cell viability, ultrastructural morphology, and nitric oxide (NO) levels were analyzed. (3) Results: Electrospun mats and their functionalization were optimized to reproduce the chemical and physical properties of the vascular intima tunica. The 3D supports were suitable for the cell culture. Ox-LDL did not affect the HUVEC behavior in the 3D models under a static environment. Conversely, high shear stress (500 µL/min, HSS) significantly decreased the cell viability, also under the ox-LDL treatment. (4) Conclusions: Endothelial cell cultures on electrospun supports exposed to HSS provide a candidate in vitro model for investigating the endothelial dysfunction in atherosclerosis research. Technical improvements to the experimental setting are necessary for validating and standardizing the suggested 3D model. Full article

Skeletal muscle diseases often exhibit fiber-type-specific characteristics and pose substantial clinical challenges, necessitating innovative therapies. The extracellular matrix (ECM) plays a pivotal role in muscle physiology and regeneration, influencing cell differentiation. However, its specific role and mechanisms influencing muscle fiber type specification remain insufficiently understood. In this study, C2C12^GFP myoblasts were differentiated into myofibers on plates coated with fibronectin, Collagen I, and Geltrex™. Differentiation occurred successfully across all ECM substrates, resulting in myofiber formation. Quantitative polymerase chain reaction (qPCR) analysis confirmed myogenic marker expression patterns, indicating decreased Pax7 and increased Myog levels by day 7. Protein analysis through Western blot and immunofluorescence assays along with transcriptomic profiling through RNA sequencing consistently indicated that Collagen I promoted slow-type fibers development, as evidenced by increased slow myofiber protein expression and the upregulation of slow fiber-associated genes, potentially mediated by pathways involving calcineurin/NFAT, MEF2, MYOD, AMPK, PI3K/AKT, and ERK1. In contrast, fibronectin and Geltrex™ led to fast-type fiber development, with elevated fast-type fiber protein levels and upregulation of fast fiber-associated genes, possibly through activation of HIF1A, FOXO1, NFKB, and ERK2. These findings elucidate ECM-mediated muscle fiber type differentiation mechanisms, informing future targeted therapies for muscle regeneration. Full article

Titanium and its alloy scaffolds are widely utilized in clinical settings; however, their biologically inert surfaces and inherent mechanical characteristics impede osteogenesis and soft tissue integration, thereby limiting their application. Selective laser melting (SLM) was employed to fabricate scaffolds with matched cortical bone mechanical properties, achieving a composite coating of hydroxyapatite complexed with trace elements of silicon, strontium, and fluoride (mHA), along with type I collagen (Col I) and fibrinogen (Fg), thus activating the scaffold surface. Initially, we utilized the excellent adhesive properties of dopamine to co-deposit mHA and polydopamine (PDA) onto porous Ti-6Al-4V scaffolds, which was followed by immobilization of type I collagen and fibrinogen onto PDA. This bioinorganic/bioprotein composite coating, formed via PDA bonding, exhibits excellent stability. Moreover, in vitro cell experiments demonstrate excellent biocompatibility of the porous Ti-6Al-4V scaffold with composite bioactive coatings on its surface. Preosteoblasts (MC3T3-E1) and human keratinocytes (HaCaT) exhibit enhanced adhesion and proliferation activity, and the osteogenic performance of the scaffold is significantly improved. The PDA-mHA-Col I-Fg composite-coated porous titanium alloy scaffold holds significant promise in enhancing the efficacy of percutaneous bone transplantation and requires further investigation. Full article

Aim: to evaluate the bone regeneration capacity of two alloplastic biomaterials in a critical-size rat calvarial defect model. Methods: A total of 80 rats were randomized into 8 groups of 10 animals each. An Ø8 mm, critical-size calvarial defect was created, and the following treatments were randomly allocated: sham surgery, deproteinized bovine bone mineral (DBBM) + collagen membrane (CM), poly-(lactic-co-glycolic-acid) (PLGA)-coated pure phase β-tricalcium phosphate (β-TCP), or PLGA-coated 60% hydroxyapatite (HA):40%β-TCP. Animals were allowed to heal for 2 and 6 weeks. Microcomputed tomography (μCT) was used to evaluate mineralized tissue and biomaterial displacement. Histological samples were used to evaluate new bone formation. Results: μCT analysis showed no significant differences among groups for total volume of mineralized tissue or residual biomaterials. DBBM + CM showed significantly increased horizontal biomaterial displacement at 2 weeks but not at 6 weeks. Histological analysis showed that sham surgery had a significantly higher percentage of bone area fraction than the DBBM + CM and PLGA + β-TCP at 2 weeks, but not at 6 weeks. Residual biomaterial area fraction showed no significant differences among experimental groups at any healing time. Conclusions: The alloplastic biomaterials showed suitable construct integrity and retention in the defect. All biomaterials were associated with limited new bone formation comparable to the sham surgery control. Full article

Long-term solutions for cartilage repair after injury are currently being investigated, with most research aiming to exploit the regenerative and chondrogenic differentiation potential of stem-cell-based spheroids. The incorporation of the bioactive polymer CTL, a lactose-modified chitosan, into spheroids is a strategy to improve cell viability and accelerate type II collagen gene expression. In this work, the role of CTL in influencing the dynamics of spheroid formation and its interplay with cell membrane adhesion molecules (integrins and cadherins) and cytoskeletal components is elucidated. The results indicate that CTL is actively involved in the reorganization of cells into spheroids. An analysis of the effects of physical form of CTL (rehydrated polymer coating or polymer solution) in stimulating peculiar biological responses indicates that CTL matrix in spheroids facilitates an early phase of chondrogenic differentiation. Once the CTL matrix is included in spheroids, there is an increase in COL2A1 gene expression and matrix deposition, regardless of the initial physical form of CTL. Overall, these results contribute to a better understanding of the dynamics of spheroid formation in the presence of the polymer and on its bioactive role in mesenchymal stem cell spheroids. Full article

Microcirculation damage, dermal thickening, and difficulty in the spatiotemporal coordination of key platelet factor 4 (CXCL4) and transforming growth factor-β (TGF-β) contribute to the lack of effective treatments for systemic sclerosis (scleroderma, SSc). To address these challenges, we proposed a novel synergistic drug combination of ginsenoside Rk3 (CXCL4 regulator) and metformin (Met, TGF-β regulator) based on molecular docking and developed an ultra-long release, dual-target regulation hydrogel microneedle system (Rk3/Met URS MN). The rapidly dissolving tips of this hydrogel microneedle consisted of polyvinyl alcohol and polyvinylpyrrolidone, and were loaded with polydopamine-coated, coordination-induced self-assembled Rk3/Met nanomedicines. These micro-tips could spatiotemporally synchronize transdermal delivery of the hydrophobic Rk3 and hydrophilic Met, providing ultra-long release for up to 10 days with a single administration. The recombinant collagen CF-1552/oxidized pullulan-based (CAOP) hydrogel backing exhibited skin self-adhesiveness and excellent mechanical properties and could perform localized moisture retention and free radical scavenging at the lesion site. In vitro and in vivo efficacy studies, along with bioinformatics analysis of RNA sequencing, demonstrated that the Rk3/Met URS MN achieved immune modulation, anti-inflammatory effects, angiogenesis promotion, and antifibrosis in SSc through synergistic CXCL4/TGF-β dual-target regulation. Notably, on the 10th day, the dermal thickness decreased from 248.97 ± 21.3 μm to 152.7 ± 18.1 μm, with no significant difference from the normal group, indicating its significant potential in clinical applications in SSc. Full article

Innovation in oral implantology is constantly on the move, with a constant search for new biomaterials to overcome many of the limitations of the biomaterials used in current implantable medical devices. This study explores the biocompatibility of an innovative 5% calcium-to-zirconia (Ca-SZ) coating deposited by PVD on TA6V substrates for use in oral implantology. In order to determine the contribution of the Ca-SZ coating, an in vitro biocompatibility study was carried out to assess the potential influence of the Ca-SZ coating (1) on the viability and proliferation of saos-2 and HaCaT cells over a short-term exposure period of 96 h, (2) on the synthesis of pro-inflammatory cytokines, and (3) on the synthesis of osteogenic differentiation markers over a long-term exposure period of 21 days, in comparison with reference biomaterials. The sampling consisted of n = 3 biological replicates, and a p-value of <0.05 was used as the threshold for statistical significance. Viability and proliferation kinetics to WST-1 and CyQUANT NF, respectively, showed improved viability/proliferation of Ca-SZ exposed to both cell lines independently. The TNF-alpha and IL-6 assays revealed reduced levels of cytokines compared with the reference biomaterials, including the control groups. In parallel, in Saos-2 cells exposed to Ca-SZ for 21 days under osteogenic conditions increased expression of osteogenic markers, such as the synthesis of soluble collagens, alkaline phosphatase (ALP), osteopontin, and osteocalcin, reflecting dynamic and facilitated osteoblastic differentiation, which was supported by the formation of hydroxyapatite (HA) crystals observed by SEM micrograph and confirmed by EDS mapping. In conclusion, Ca-SZ demonstrates an overall better biocompatibility compared with reference biomaterials, linked to a bioactive interaction of calcium, promoting cell proliferation and differentiation for optimal osteointegration, underlining its potential as a relevant innovation for next-generation implants. Full article

Nanotopography refers to the intricate surface characteristics of materials at the sub-micron (<1000 nm) and nanometer (<100 nm) scales. These topographical surface features significantly influence the physical, chemical, and biological properties of biomaterials, affecting their interactions with cells and surrounding tissues. The development of nanostructured surfaces of polymeric nanocomposites has garnered increasing attention in the fields of tissue engineering and regenerative medicine due to their ability to modulate cellular responses and enhance tissue regeneration. Various top-down and bottom-up techniques, including nanolithography, etching, deposition, laser ablation, template-assisted synthesis, and nanografting techniques, are employed to create structured surfaces on biomaterials. Additionally, nanotopographies can be fabricated using polymeric nanocomposites, with or without the integration of organic and inorganic nanomaterials, through advanced methods such as using electrospinning, layer-by-layer (LbL) assembly, sol–gel processing, in situ polymerization, 3D printing, template-assisted methods, and spin coating. The surface topography of polymeric nanocomposite scaffolds can be tailored through the incorporation of organic nanomaterials (e.g., chitosan, dextran, alginate, collagen, polydopamine, cellulose, polypyrrole) and inorganic nanomaterials (e.g., silver, gold, titania, silica, zirconia, iron oxide). The choice of fabrication technique depends on the desired surface features, material properties, and specific biomedical applications. Nanotopographical modifications on biomaterials’ surface play a crucial role in regulating cell behavior, including adhesion, proliferation, differentiation, and migration, which are critical for tissue engineering and repair. For effective tissue regeneration, it is imperative that scaffolds closely mimic the native extracellular matrix (ECM), providing a mechanical framework and topographical cues that replicate matrix elasticity and nanoscale surface features. This ECM biomimicry is vital for responding to biochemical signaling cues, orchestrating cellular functions, metabolic processes, and subsequent tissue organization. The integration of nanotopography within scaffold matrices has emerged as a pivotal regulator in the development of next-generation biomaterials designed to regulate cellular responses for enhanced tissue repair and organization. Additionally, these scaffolds with specific surface topographies, such as grooves (linear channels that guide cell alignment), pillars (protrusions), holes/pits/dots (depressions), fibrous structures (mimicking ECM fibers), and tubular arrays (array of tubular structures), are crucial for regulating cell behavior and promoting tissue repair. This review presents recent advances in the fabrication methodologies used to engineer nanotopographical microenvironments in polymeric nanocomposite tissue scaffolds through the incorporation of nanomaterials and biomolecular functionalization. Furthermore, it discusses how these modifications influence cellular interactions and tissue regeneration. Finally, the review highlights the challenges and future perspectives in nanomaterial-mediated fabrication of nanotopographical polymeric scaffolds for tissue engineering and regenerative medicine. Full article

For organ-on-a-chip (OoC) engineering, the use of biocompatible coatings and materials is not only recommended but essential. Extracellular matrix (ECM) components are commonly used as coatings due to their effects on cell orientation, protein expression, differentiation, and adhesion. Among the most frequently used coatings are collagen, fibronectin, and Matrigel, according to the specific cell type and intended OoC application. Additionally, materials such as polydimethylsiloxane (PDMS), thermoplastics, chitosan, and alginate serve as scaffolding components due to their biomechanical properties and biocompatibility. Here, we discuss some of the most employed coating techniques, including SAMs, dip coating, spin coating, microcontact printing, and 3D bioprinting, each offering advantages and drawbacks. Current challenges comprise enhancing biocompatibility, exploring novel materials, and improving scalability and reproducibility. Full article