Search Results (83)

Poly(glycerol sebacate) (PGS) is a biodegradable elastomer with high potential for tissue engineering. However, its limited structural stability and degradation control restrict broader biomedical applications. This study presents an integrated fabrication strategy for highly porous PGS-IPDI scaffolds reinforced with two types of hydroxyapatite of distinct origin (HAP_B and HAP_ICMB). By combining low-temperature urethane crosslinking with thermally induced phase separation and salt leaching, we obtained scaffolds with interconnected micro–macroporous architectures and exceptionally high porosity (up to 98%). The comparative incorporation of phase-pure nanometric HAP_B and biphasic HAP_ICMB enabled the identification of composition-dependent differences in water uptake, structural stability, and mineralization tendencies. Furthermore, degradation behavior was systematically evaluated in four physiologically relevant media (PBS, SBF, artificial saliva, Ringer’s solution), revealing distinct degradation pathways associated with each environment. The results provide new insight into how hydroxyapatite type and incubation medium collectively govern the long-term performance of chemically crosslinked PGS-based scaffolds. Full article

Carboxyxanthones containing carboxylic acid groups linked to lipophilic aromatic rings resemble the key pharmacophoric features of many nonsteroidal anti-inflammatory drugs (NSAIDs). This structural similarity makes them attractive scaffolds for the development of new anti-inflammatory agents. This study describes the production, cytocompatibility, and anti-inflammatory potential of ten carboxyxanthones (1–10) and two intermediates (11–12) by evaluating their effects on key pro-inflammatory mediators, namely interleukin 6 (IL-6) and prostaglandin E2 (PGE₂). As these compounds are produced by distinct mechanisms, their multi-target potential will be evaluated. Carboxyxanthones were obtained by multi-step pathways using different synthetic approaches through classical benzophenone or diaryl ether intermediates synthesis followed by intramolecular acylation. To the best of our knowledge, the synthesis of carboxyxanthones 3 and 5 is described herein for the first time. All tested compounds were cytocompatible with lipopolysaccharide (LPS)-stimulated macrophages. The most notable carboxyxanthones were 3, 4, 7, and 8, which were able to significantly reduce IL-6 production by approximately 60%. Molecular docking simulations between compounds 1–12 and cyclooxygenase-2 were conducted to characterize the structural features underlying molecular recognition, and to identify the most promising candidates for subsequent PGE₂ assays. Carboxyxanthones 3, 5, and 6, as well as intermediate 12, were predicted to be the best. In the human in vitro inflammation model used, carboxyxanthone 6 exhibited the most potent and consistent inhibitory effect on PGE₂ production. At the highest concentration tested (100 µM), it presented an efficacy comparable to that of celecoxib. Carboxyxanthones 3 and 5 demonstrated a biphasic effect, decreasing and increasing PGE₂ production at lower (5, 12.5, and 25 µM) and higher (50 and 100 µM) concentrations, respectively. These results highlight the potential of carboxyxanthones as promising modulators of inflammatory pathways, paving the way for further studies aimed at elucidating their mechanisms of action, optimizing structural features, and assessing their safety and therapeutic potential in relevant disease models. Full article

This study aimed to engineer nanofibrous scaffolds that prioritize architecture, rather than relying solely on the drug, to achieve reproducible, long-acting local therapies. Cotton-wool-like fiber, three-dimensional (3D) poly(L-lactic acid)/polyethene glycol (PLLA/PEG) blend scaffolds were fabricated using solution blow spinning (SBS) as a customizable encapsulation platform for controlled antibiotic release. Morphological and wettability analyses were performed by scanning electron microscopy (SEM) and pendant-drop contact angle measurements, respectively. Fiber diameters were quantified using ImageJ. The chemical composition and thermal behavior were investigated by Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). In vitro, assays were conducted to assess the antimicrobial activity of vancomycin-loaded scaffolds against Staphylococcus aureus (disk diffusion method), as well as their cytocompatibility (Live/Dead assay in Vero cells) and hemocompatibility (ASTM F756-17 hemolysis test). All biological data were statistically analyzed using ANOVA with Tukey’s post-test, Mann–Whitney, and paired t-tests, with significance set at p ≤ 0.05. Structural optimization identified PLLA/PEG 85:15 as the most stable composition, producing homogeneous mats with high porosity and rapid wettability. Incorporation of vancomycin (10 wt.%) reduced the fiber diameter (0.23 ± 0.11 µm) compared with unloaded scaffolds (0.32 ± 0.17 µm), indicating drug–polymer interactions that modulated jet elongation. FTIR, DSC, and TGA analyses confirmed polymer miscibility and stabilization of VMC within the fibrous matrix, with no signs of degradation. Drug release exhibited a biphasic profile, with an initial burst during the first 72 h. PLLA/PEG–VMC scaffolds produced larger inhibition zones against S. aureus (18.55 mm ± 1.2 to 6.63 mm ± 0.2 at 120 h) compared with free VMC (12.91 mm ± 3.8 to 4.07 mm ± 0.6291), while blank scaffolds were inactive. Hemolysis remained within the range 2% < PLLA/PEG–VMC < 5%, indicating acceptable hemocompatibility according to ASTM standards. Although VCM-loaded PLLA/PEG scaffolds slightly reduced Vero cell viability, no statistically significant differences were observed compared with the control group. These findings demonstrate that the architecture of nanofibers presents itself as a potential platform for antimicrobial therapy with topical vancomycin in potential applications such as wound dressings or implant coatings. Full article

The synthesis of a small library of fused Cyclic Aryl Amino Carbon (f-CArAC) carbene precursors in the form of 1,1,2,4-tetraaryl-1H-isoindol-2-ium triflate (6), (7-R) (R = ^tBu, CF₃) or 3,3-dimethyl-2,8-bis-arene-substituted-3,4-dihydro-isoquinolin-2-ium hydrogen-dichloride (8) and 2,4,8-tri(substituted)-isoquinolin-2-ium tosylate salts (12) has been achieved. All of them feature an arene incorporated on the annulated benzene ring of the corresponding heterocycle, introduced at the early stages of their synthesis via the Suzuki cross-coupling reaction between 2,6-dibromo-benzaldehyde and the desired aryl boronic acid. The terphenyl-2′carbaldehyde by-products of this Suzuki reaction are useful starting points for the preparation of two new iminium iodide salts (10-R) (R = H, CF₃) as potential precursors to access ACyclic Amino Carbon (ACAC) carbenes. Compounds (6) and (7-^tBu) react readily with hydroxide either in THF or in a biphasic Et₂O/aqueous OH⁻ solution to produce the substituted isoindolinols (13) and (14), respectively. The thermal dehydration of the former generates the corresponding f-CArAC carbene in situ, which is trapped by Cu(I)Cl furnishing, a rare example of a two-coordinate Cu(I) complex (15) supported by this new ligand scaffold. Full article

Biphasic calcium phosphate (BCP)scaffolds comprising hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP) were produced from ultra-pure precursors and processed under an α-TCP–avoiding schedule (1100 °C, 2 h). Quantitative X-ray diffraction (Rietveld/Profex) detected no α-TCP above the ~1 wt% limit of detection and quantified post-sintering phase fractions (wt% HA/β-TCP): 99.26/0.74, 68.51/31.49, and 27.57/72.43. Across compositions, SEM/ImageJ yielded similar mean macropore sizes (≈71–80 µm), while open porosity increased with the HA fraction (27.5 ± 1.8%, 39.1 ± 2.0%, 57.1 ± 2.4%). Compressive strength decreased accordingly (1.07 ± 0.25, 0.24 ± 0.01, 0.05 ± 0.02 MPa), consistent with non-load-bearing use. In ISO-compliant simulated body fluid (28 d), medium pH remained stable (7.33–7.43); mass loss and early Ca²⁺ depletion increased with β-TCP content, consistent with more extensive surface apatite formation in β-TCP-rich scaffolds. Collectively, these data are consistent with a composition-dependent sequence—β-TCP content → densification/porosity → strength → degradation/apatite kinetics—within the tested conditions and inform parameter-based tuning of BCP scaffolds for non-load-bearing indications (e.g., alveolar ridge preservation, craniofacial void filling). Full article

Background: Maxillomandibular bone defects present a complex challenge in regenerative medicine due to anatomical and functional intricacies. Calcium phosphate (CP)-based biomaterials have emerged as promising bone graft substitutes due to their biocompatibility, osteoconductivity, and bioactivity. Aim: This Review highlights recent clinical and experimental advancements in CP-based biomaterials for maxillomandibular bone regeneration, bridging the gap from bench to bedside. Method: An in vitro, in vivo, and clinical literature review was conducted to evaluate the performance of CP ceramics, including hydroxyapatite (HA), tricalcium phosphate (TCP), biphasic ceramics, and novel composites with polymers, growth factors, and nanoparticles. Results: Calcium phosphate-based biomaterials demonstrate excellent bone regeneration potential, with Beta-tricalcium phosphate (β-TCP) and HA being the most widely utilized. Composite scaffolds and 3-dimensional (3D)-printed constructs show enhanced mechanical properties and biological integration. Clinical trials have confirmed the safety and efficacy of CP-based materials, yielding promising outcomes in osteoconduction and defect healing. However, limitations persist regarding mechanical strength and long-term degradation profiles. Conclusions: CP-based biomaterials offer significant clinical promise for maxillomandibular bone regeneration. Continued advancements in scaffold design and biofunctionalization are crucial for overcoming current limitations and fully realizing their therapeutic potential. Full article

The intervertebral disc (IVD) is a biphasic tissue in which the extracellular matrix (ECM) acts as a structural scaffold and regulates hydration and solute transport. The influence of hydration on the swelling and mechanical properties of the IVD, particularly the annulus fibrosus (AF), is not fully described in the literature. Hydration is assumed to affect inter- and intramolecular hydrogen bonding and hydrophilic interactions, thereby modulating tissue mechanics. This study aimed to assess the effect of hydration time on free swelling of AF and its impact on mechanical performance. AF specimens were divided into five groups, hydrated for 0, 10, 20, 30, or 40 min and subjected to uniaxial tensile testing until failure. Swelling-related geometric changes were correlated with tensile properties. Results demonstrated that hydration duration significantly influenced AF’s structural and mechanical characteristics in anterior and posterior IVD regions. Hydration increases rapidly within 10–20 min, causing cross-sections to swell, stress capacity to decrease, and stiffness to remain unchanged. However, after 40 min, the tissue becomes swollen beyond physiological balance. These findings identify hydration duration as a critical factor regulating AF function and provide important insights for experimental standardization, numerical modeling, and hydrogels designed for intervertebral disc regeneration. Full article

Electroactive biomaterials are a key emerging technology for the treatment of neural damage. Conducting polymer-coated carbon microfibers are particularly useful for this application because they provide directional support for cell growth and tissue repair and simultaneously allow for ultrasensitive recording and stimulation of neural activity. Here, we report in vitro experiments investigating the biology of Schwann cells (SCs), a major player in peripheral nerve regeneration, on electroconducting microfibers. The optimal molecular composition of the cell substrate and cell culture medium was studied for SCs dissociated from rat and pig peripheral nerves. The substrate molecules were then attached to carbon microfibers coated with poly (3,4-ethylenedioxythiophene) doped with poly [(4-styrenesulfonic acid)-co-(maleic acid)] (PCMFs), which served as an electroactive scaffold for culturing nerve explants. Biphasic electrical stimulation (ES) was applied through the microfibers, and its effects on cell proliferation and migration were assessed in different cell culture media. Rodent and porcine SCs avidly migrated on PCMFs functionalized with a complex of poly-L-lysine, heparin, basic fibroblast growth factor, and fibronectin. Serum and forskolin/heregulin increased, by two-fold and four-fold, the number of SCs on PCMFs, respectively, and ES further doubled cell numbers without favoring fibroblast proliferation. ES additionally increased SC migration. These results provide a baseline for using biofunctionalized PCMFs in peripheral nerve repair. Full article

Regenerative endodontics seeks to restore the vascularized pulp–dentin complex following conventional root canal therapy, yet reliable neovascularization within the constrained root canal remains a key challenge. This study investigates the development of an injectable, dual-curing hydrogel based on methacrylated decellularized amniotic membrane (dAM-MA) and compares its performance to a conventional gelatin methacryloyl (GelMA). The dAM-MA platform was designed for biphasic release, incorporating both free vascular endothelial growth factor (VEGF) for an initial burst and matrix-metalloproteinase-cleavable VEGF conjugates for sustained delivery. The dAM-MA hydrogel achieved shape-fidelity via thermal gelation at 37 °C and possessed tunable stiffness (0.5–7.8 kPa) after visible-light irradiation. While showing high cytocompatibility comparable to GelMA (>125% hDPSC viability), the dAM-MA platform markedly outperformed the control in promoting endothelial tube formation (up to 800 µm total length; 42 branch points at 96 h). The biphasic VEGF release from dAM-MA matched physiological injury kinetics, driving both early chemotaxis and late vessel maturation. These results demonstrate that dAM-MA hydrogels combine native extracellular matrix complexity with practical, dual-curing injectability and programmable VEGF kinetics, offering a promising scaffold for minimally invasive pulp–dentin regeneration. Full article

This systematic review aimed to evaluate the effectiveness of teriparatide (TP) in guided bone regeneration (GBR). An electronic search without language or date restrictions was performed in PubMed, Web of Science, Scopus, Scielo, and gray literature for articles published until June 2025. Inclusion criteria considered studies evaluating the effect of TP on bone regeneration, analyzed using SYRCLE’s Risk of Bias tool. Twenty-four preclinical studies were included, covering diverse craniofacial models (mandibular, calvarial, extraction sockets, sinus augmentation, distraction osteogenesis, segmental defects) and employing systemic or local TP administration. Teriparatide consistently enhanced osteogenesis, graft integration, angiogenesis, and mineralization, with potentiated effects when combined with various biomaterials, including polyethylene glycol (PEG), hydroxyapatite/tricalcium phosphate (HA/TCP), biphasic calcium phosphate (BCP), octacalcium phosphate collagen (OCP/Col), enamel matrix derivatives (EMDs), autografts, allografts, xenografts (Bio-Oss), strontium ranelate, and bioactive glass. Critically, most studies presented a moderate-to-high risk of bias, with insufficient randomization, allocation concealment, and blinding, which limited the internal validity of the findings. TP shows promising osteoanabolic potential in guided bone regeneration, enhancing bone formation, angiogenesis, and scaffold integration across preclinical models. Nonetheless, its translation to clinical practice requires well-designed human randomized controlled trials to define optimal dosing strategies, long-term safety, and its role in oral and craniomaxillofacial surgical applications. Full article

The present study reports on the manufacturing of biphasic calcium phosphate (BCP) honeycomb scaffolds with tailored microporous walls using phase separation-assisted digital light processing (PS-DLP). To create micropores in BCP walls, camphene was used as the pore-forming agent for preparing BCP suspensions, since it could be completely dissolved in photopolymerizable monomers composed of triethylene glycol dimethacrylate (TEGDMA) and polyethylene glycol diacrylate (PEGDA) and then undergo phase separation when placed at 5 °C. Therefore, solid camphene crystals could be formed in phase-separated BCP layers and then readily removed via sublimation after the photopolymerization of monomer networks embedding BCP particles by DLP. This approach allowed for tight control over the microporosity of BCP walls by adjusting the camphene content. As the camphene content increased from 40 to 60 vol%, the microporosity increased from ~38 to ~59 vol%. Consequently, the overall porosity of dual-scale porosity scaffolds increased from ~51 to ~67 vol%, while their compressive strength decreased from ~70.4 to ~13.7 MPa. The mass transport ability increased remarkably with an increase in microporosity. Full article

This study aimed to synthesize and characterize cassava starch-based (S) scaffolds functionalized with decellularized extracellular matrix (dECM) and isosorbide dinitrate (ISDN) for wound healing. The scaffolds were synthesized via the casting method and evaluated for physicochemical, mechanical, and morphological properties, as well as ISDN release and hemocompatibility. Swelling and degradation tests revealed a biphasic behavior, with high water absorption followed by controlled degradation. The ISDN release followed a biphasic pattern, fitting the Korsmeyer–Peppas model. Hemolysis tests confirmed biocompatibility, with hemolysis levels below 2%. Among the formulations, the scaffold containing 12.5% ECM and 40 mg ISDN exhibited optimal mechanical stability, controlled drug release, and biocompatibility. These findings suggest that starch/ECM/ISDN scaffolds hold potential for wound healing applications. Further studies should focus on in vivo evaluation and cytotoxicity assessments to confirm their clinical applicability. Full article

Infection control and bone regeneration remain critical challenges in bone defect treatment. We developed a 3D-printed scaffold incorporating copper-based metal–organic framework-74 (Cu-MOF-74) within a polycaprolactone/hydroxyapatite composite. The synthesized Cu-MOF-74 exhibited a well-defined crystalline structure and rod-like morphology, as confirmed by TEM, EDS, FTIR, and XRD analyses. The scaffolds exhibited hierarchical pores (100–200 μm) and demonstrated tunable hydrophilicity, as evidenced by the water contact angles decreasing from 103.3 ± 2.02° (0% Cu-MOF-74) to 63.60 ± 1.93° (1% Cu-MOF-74). A biphasic Cu²⁺ release profile was observed from the scaffolds, reaching cumulative concentrations of 98.97 ± 3.10 ppm by day 28. Antimicrobial assays showed concentration-dependent efficacy, with 1% Cu-MOF-74 scaffolds achieving 90.07 ± 1.94% and 80.03 ± 2.17% inhibition against Staphylococcus aureus and Escherichia coli, respectively. Biocompatibility assessments using bone marrow-derived mesenchymal stem cells revealed enhanced cell proliferation at Cu-MOF-74 concentrations ≤ 0.2%, while concentrations ≥ 0.5% induced cytotoxicity. Osteogenic differentiation studies highlighted elevated alkaline phosphatase activity and mineralization in scaffolds with 0.05–0.2% Cu-MOF-74 scaffolds, particularly at 0.05% Cu-MOF-74 scaffolds, which exhibited the highest calcium deposition and upregulation of bone sialoprotein and osteopontin expression. These findings demonstrate the dual functional efficacy of Cu-MOF-74/PCL/HAp scaffolds in promoting both infection control and bone regeneration. These optimized Cu-MOF-74 concentrations (0.05–0.2%) effectively balance antimicrobial and osteogenic properties, presenting a promising strategy for bone defect repair in clinical applications. Full article

Background/Objectives: Delays in bone healing and complications of remodeling constitute a major medical problem—particularly in older adults and patients with comorbidities. Current therapeutic approaches are based on strategies that promote bone regeneration. We recently identified a disaccharide compound (DP2) that enhances in vitro mineralization in human osteoblast cells via the early activation of Runx2 and the induction of osteoblast differentiation. Methods: First, a calcium quantification assay was performed to assess mineralization in MC3T3-E1 cells. Next, microcomputed tomography and histological analyses were used to examine in vivo bone repair in a rat 5 mm cranial defect model following the implantation of DP2 coupled to a micro/macroporous biphasic CaP ceramic (MBCP⁺) or collagen scaffold. Results: Here, we demonstrated that DP2 induced osteogenic differentiation and significantly elevated calcium matrix deposition in the murine preosteoblast cell line MC3T3-E1. We found that treatment with DP2 coupled to MBCP⁺ repaired the calvarial defect on post-implantation day 91. It significantly increased bone mineral density starting on day 29 post-treatment. In addition, DP2 did not induce ectopic bone formation. Conclusions: Taken as a whole, these results show that DP2 is a promising candidate treatment for delayed bone healing. Full article

The objective of this work is to review the literature on the use of three-dimensional scaffolds obtained by printing for the regeneration of bone defects in the maxillofacial area. The research question asked was: what clinical experiences exist on the use of bone biomaterials manufactured by CAD/CAM in the maxillofacial area? Prospective and retrospective studies and randomized clinical trials in humans with reconstruction area in the maxillofacial and intraoral area were included. The articles had to obtain scaffolds for bone reconstruction that were designed by computer processing and printed in different materials. Clinical cases, case series, in vitro studies and those that were not performed in humans were excluded. Six clinical studies were selected that met the established inclusion criteria. The selected studies showed heterogeneity in their objectives, materials used and types of regenerated bone defects. A high survival rate was found for dental implants placed on 3D-printed scaffolds, with rates ranging from 94.3% to 98%. The materials used included polycaprolactone, coral-derived hydroxyapatite, biphasic calcium phosphate (BCP) and bioceramics. The use of CAD/CAM technology is seen as key for satisfying variations in the shapes and requirements of different fabrics and size variations between different individuals. Furthermore, the possibility of using the patient’s own stem cells could revolutionize the way bone defects are currently treated in oral surgery. The results indicate a high survival rate of dental implants placed on 3D-printed scaffolds, suggesting the potential of this technology for bone regeneration in the maxillofacial mass. Full article