Search Results (215)

In recent years, apatite-based materials have garnered significant interest, particularly for applications in tissue engineering. Apatite is most commonly employed as a coating for metallic implants, as a component in composite materials, and as scaffolds for bone and dental tissue regeneration. Among its various forms, hydroxyapatite (HAP) is the most widely used, owing to its natural occurrence in human and animal hard tissues. An emerging area of research involves the use of fluoride-substituted apatite, particularly fluorapatite (FAP), which can serve as a direct fluoride source at the implant site, potentially offering several biological and therapeutic advantages. However, substituting HAP with FAP may lead to unforeseen changes in material behavior due to the differing physicochemical properties of these two calcium phosphate phases. This study investigates the effects of replacing hydroxyapatite with fluorapatite in ceramic–polymer composite materials incorporating β-1,3-glucan as a bioactive polymeric binder. The β-1,3-glucan polysaccharide was selected for its proven biocompatibility, biodegradability, and ability to form stable hydrogels that promote cellular interactions. Nitrogen adsorption analysis revealed that FAP/glucan composites had a significantly lower specific surface area (0.5 m²/g) and total pore volume (0.002 cm³/g) compared to HAP/glucan composites (14.15 m²/g and 0.03 cm³/g, respectively), indicating enhanced ceramic–polymer interactions in fluoride-containing systems. Optical profilometry measurements showed statistically significant differences in profile parameters (e.g., Rp: 134 μm for HAP/glucan vs. 352 μm for FAP/glucan), although average roughness (Ra) remained similar (34.1 vs. 27.6 μm, respectively). Microscopic evaluation showed that FAP/glucan composites had smaller particle sizes (1 μm) than their HAP counterparts (2 μm), despite larger primary crystal sizes in FAP, as confirmed by TEM. XRD analysis indicated structural differences between the apatites, with FAP exhibiting a reduced unit cell volume (524.6 ų) compared to HAP (528.2 ų), due to substitution of hydroxyl groups with fluoride ions. Spectroscopic analyses (FTIR, Raman, ³¹P NMR) confirmed chemical shifts associated with fluorine incorporation and revealed distinct ceramic–polymer interfacial behaviors, including an upfield shift of PO₄³⁻ bands (964 cm⁻¹ in FAP vs. 961 cm⁻¹ in HAP) and OH vibration shifts (3537 cm⁻¹ in FAP vs. 3573 cm⁻¹ in HAP). The glucan polymer showed different hydrogen bonding patterns when combined with FAP versus HAP, as evidenced by shifts in polymer-specific bands at 888 cm⁻¹ and 1157 cm⁻¹, demonstrating that fluoride substitution significantly influences ceramic–polymer interactions in these bioactive composite systems. Full article

Hydrogels have emerged as promising biomaterials for oral tissue regeneration thanks to their high-water content, excellent biocompatibility, and ability to mimic native tissue environments. These versatile materials can be tailored to support cell adhesion, proliferation, and differentiation, making them suitable for repairing both soft and hard oral tissues. When engineered from natural polymers and enriched with bioactive agents, hydrogels offer enhanced regenerative potential. Biopolymer-based hydrogels, derived from materials such as chitosan, alginate, collagen, hyaluronic acid, and gelatin, are particularly attractive due to their biodegradability, bioactivity, and structural similarity to the extracellular matrix, creating an optimal microenvironment for cell growth and tissue remodeling. Recent innovations have transformed these systems into multifunctional platforms capable of supporting targeted regeneration of periodontal tissues, alveolar bone, oral mucosa, dental pulp, and dentin. Integration of bioactive molecules, particularly essential oils, bio-derived constituents, cells, or growth factors, has introduced intrinsic antimicrobial, anti-inflammatory, and antioxidant functionalities, addressing the dual challenge of promoting tissue regeneration while at the same time attenuating microbial contamination in the oral environment. This review explores the design strategies, material selection, functional properties, and biomedical applications in periodontal therapy, guided tissue regeneration, and implant integration of natural polymer-based hydrogels enriched with bioactive factors, highlighting their role in promoting oral tissue regeneration. In addition, we discuss current challenges related to mechanical stability, degradation rates, and clinical translation, while highlighting future directions for optimizing these next-generation bioactive hydrogel systems in regenerative dentistry. Full article

Background/Objectives: Recent advancements in biomaterials aimed at closely mimicking natural biological tissues hold great promise for hard tissue regeneration and controlled drug release due to their superior physical, chemical, and biological properties. This study aimed to develop multi-ion doped calcium hydroxyapatite (HAp) scaffolds with chitosan-based coatings for localized drug delivery, incorporating a novel hydrazone compound with potential anticancer activity. Methods: HAp powders doped with magnesium (Mg²⁺), strontium (Sr²⁺), and varying fluoride (F⁻) contents (0–2 mol.%) were synthesized via a hydrothermal method. Scaffolds were fabricated using the sponge replica technique and subsequently coated with chitosan or a chitosan–hydrazone blend. Dopant incorporation was confirmed by electron dispersive X-ray spectroscopy (EDS). Phase composition and morphology were analyzed via X-ray diffraction (XRD) and scanning electron microscopy (SEM). Mechanical properties, bioactivity, cytotoxicity, and hydrazone release profiles were systematically evaluated. Results: EDS confirmed successful incorporation of Mg²⁺ and Sr²⁺ in all powders, while F⁻ was detected only in powders with 1 and 2 mol.% fluoride. XRD and SEM revealed the phase composition and scaffold microstructure. Chitosan coatings significantly improved scaffold compressive strength and reduced degradation rate, indicating enhanced stability in biological environments. The coated scaffolds supported MRC-5 fibroblast viability. The hydrazone compound exhibited dose-dependent antitumor cytotoxicity comparable to cisplatin and showed sustained release from scaffolds for up to 15 days. Conclusions: The combination of multi-ion doped HAp scaffolds and chitosan–hydrazone coatings provides a promising platform for bone tissue engineering and localized cancer therapy, demonstrating both mechanical stability and controlled, sustained drug release. Full article

Orofacial Mesenchymal Stem Cells (OMSCs) are an attractive and promising tool for tissue regeneration, with their potential for craniofacial bone repair being a primary focus of research. A key advantage driving their clinical interest is their accessibility from tissues that are often discarded, such as exfoliated deciduous teeth, which circumvents the ethical concerns and donor site morbidity associated with other stem cell sources. The high proliferation ability and multi-differentiation capacity of OMSCs make them a unique resource for tissue engineering. Recently, OMSCs have been explored in the restoration of the heart and skin, treatment of oral mucosal lesions, and regeneration of hard connective tissues such as cartilage. Beyond their direct regenerative capabilities, OMSCs possess potent immunomodulatory functions, enabling them to regulate the immune system in various inflammatory disorders through the secretion of cytokines. This review offers an in-depth update regarding the therapeutic possibilities of OMSCs, highlighting their roles in the regeneration of bone and various tissues, outlining their immunomodulatory capabilities, and examining the essential technologies necessary for their clinical application. Full article

Nanotechnologies bring a rapid paradigm shift in hard and soft bone tissue regeneration (BTR) through unprecedented control over the nanoscale structures and chemistry of biocompatible materials to regenerate the intricate architecture and functional adaptability of bone. This review focuses on the transformative analyses and prospects of current and next-generation nanomaterials in designing bioactive bone scaffolds, emphasizing hierarchical architecture, mechanical resilience, and regenerative precision. Mainly, this review elucidated the innovative findings, new capabilities, unmet challenges, and possible future opportunities associated with biocompatible inorganic ceramics (e.g., phosphates, metallic oxides) and the United States Food and Drug Administration (USFDA) approved synthetic polymers, including their nanoscale structures. Furthermore, this review demonstrates the newly available approaches for achieving customized standard porosity, mechanical strengths, and accelerated bioactivity to construct an optimized nanomaterial-oriented scaffold. Numerous strategies including three-dimensional bioprinting, electro-spinning techniques and meticulous nanomaterials (NMs) fabrication are well established to achieve radical scientific precision in BTR engineering. The contemporary research is unceasingly decoding the pathways for spatial and temporal release of osteoinductive agents to enhance targeted therapy and prompt healing processes. Additionally, successful material design and integration of an osteoinductive and osteoconductive agents with the blend of contemporary technologies will bring radical success in this field. Furthermore, machine learning (ML) and artificial intelligence (AI) can further decode the current complexities of material design for BTR, notwithstanding the fact that these methods call for an in-depth understanding of bone composition, relationships and impacts on biochemical processes, distribution of stem cells on the matrix, and functionalization strategies of NMs for better scaffold development. Overall, this review integrated important technological progress with ethical considerations, aiming for a future where nanotechnology-facilitated bone regeneration is boosted by enhanced functionality, safety, inclusivity, and long-term environmental responsibility. Therefore, the assimilation of a specialized research design, while upholding ethical standards, will elucidate the challenge and questions we are presently encountering. Full article

In the context of critical challenges in curcumin-modified polyurethane synthesis—including limited curcumin bioavailability and suboptimal biodegradability/biocompatibility—a novel polyurethane material (Cur-PU) with good mechanical, shape memory, pH-responsive, and biocompatibility was synthesized via a one-pot, two-step synthetic protocol in which HO-PCL-OH served as the soft segment and curcumin was employed as the chain extender. The experimental results demonstrate that with the increase in Cur units, the crystallinity of the Cur-PU material decreases from 32.6% to 5.3% and that the intensities of the diffraction peaks at 2θ = 21.36°, 21.97°, and 23.72° in the XRD pattern gradually diminish. Concomitantly, tensile strength decreased from 35.5 MPa to 19.3 MPa, and Shore A hardness declined from 88 HA to 65 HA. These observations indicate that the sterically hindered benzene ring structure of Cur imposes restrictions on HO-PCL-OH crystallization, leading to lower crystallinity and retarded crystallization kinetics in Cur-PU. As a consequence, the material’s tensile strength and hardness are diminished. Except for the Cur-PU-3 sample, all other variants exhibited exceptional shape-memory functionality, with R_f and R_r exceeding 95%, as determined by three-point bending method. Analogous to pure curcumin solutions, Cur-PU solutions demonstrated pH-responsive chromatic transitions: upon addition of hydroxide ion (OH⁻) solutions at increasing concentrations, the solutions shifted from yellow-green to dark green and finally to orange-yellow, enabling sensitive pH detection across alkaline gradients. Hydrolytic degradation studies conducted over 15 weeks in air, UPW, and pH 6.0/8.0 phosphate buffer solutions revealed mass loss <2% for Cur-PU films. Surface morphological analysis showed progressive etching with the formation of micro-to-nano-scale pores, indicative of a surface-erosion degradation mechanism consistent with pure PCL. Biocompatibility assessments via L929 mouse fibroblast co-culture experiments demonstrated ≥90% cell viability after 72 h, while relative red blood cell hemolysis rates remained below 5%. Collectively, these findings establish Cur-PU as a biocompatible material with tunable mechanical properties, and pH responsiveness, underscoring its translational potential for biomedical applications such as drug delivery systems and tissue engineering scaffolds. Full article

Lysosomal storage disorders (LSDs) constitute a group of monogenic systemic diseases resulting from deficiencies in specific lysosomal enzymes that cause the intralysosomal accumulation of non- or partially degraded substrates, leading to lysosomal dysfunction. In some cases of LSDs, the bone is more severely affected, thus producing skeletal manifestations in patients. Current therapies, such as enzyme replacement therapy (ERT) and gene therapy (GT), show limited efficacy in correcting skeletal abnormalities. Increasing evidence suggests that microenvironmental disturbances also contribute significantly to disease pathogenesis. Therefore, therapeutic strategies targeting lysosomal dysfunction and microenvironmental dysregulation are needed. Mesenchymal stem-cell-derived extracellular vesicles (MSC-EVs) are emerging as promising candidates in regenerative medicine due to their immunomodulatory, pro-regenerative, and paracrine properties. MSC-EVs have shown potential to modulate the microenvironment and favor tissue repair in bone-related disorders such as osteoarthritis and osteoporosis. Interestingly, MSC-EVs can be engineered to reach the bone and carry therapeutics, including ERT- and GT-related molecules, enabling targeted delivery to hard-to-reach bone regions. This review describes the main features of MSC-EVs and discusses the therapeutic potential of MSC-EVs as a potential cell-free strategy for bone-affected LSDs. Full article

The influence of L-lactide content (between 15% and 43%) on the degradation of biodegradable polyurethanes (PUs) for tissue engineering was systematically addressed in this study. An ideal tissue scaffold should exhibit a mechanical response and degradability appropriate for the host tissue. To achieve it, polyols containing ε-caprolactone and L-lactide moieties were used, with the random distribution of lactide units disrupting the regularity, and hence the crystallinity, of poly(caprolactone) segments, facilitating their degradation. The biodegradable PUs were synthesised using these copolymers as soft segments and were characterised through various physicochemical techniques, including bioassays and water absorption measurements. It was determined that mechanical behaviour and water absorption depended significantly on molecular weight, L-lactide content in the soft segment, and the crystallinity of the hard segment. Additionally, two types of chain extenders were also evaluated: hydrolysable and non-hydrolysable. PUs based on hydrolysable chain extenders achieved higher molecular weights and exhibited better mechanical performance than their non-hydrolysable counterparts. To assess the cytocompatibility of these materials, an endothelial model was used, involving metabolic activity and DNA content analysis. The results demonstrated good cell adhesion and the absence of toxicity, confirming the viability of cell growth on the surfaces of these biodegradable PUs. The PUs developed in this study exhibited a low initial modulus and adjustable mechanical properties, highlighting their potential application in tissue engineering as biodegradable and biocompatible biomedical materials. Full article

Compared with acute wounds, typical chronic wounds (infection, burn, and diabetic wounds) are susceptible to bacterial infection and hard to heal. As for the complexity of chronic wounds, biocompatible hydrogel dressings can be employed to regulate the microenvironment and accelerate wound healing with their controllable physical and chemical properties. Recently, various nanomaterials have been introduced into hydrogel networks to prepare functional nanocomposite hydrogels. Among them, carbon-based nanomaterials (CBNs) have attracted wide attention in the biomedical field due to their outstanding physicochemical properties. However, comprehensive reviews on the use of CBNs for multifunctional hydrogel wound dressings in the past 10 years are very scarce. This review focuses on the research progress on hydrogel dressings made with typical CBNs. Specifically, a series of CBNs (carbon dots, graphene quantum dots, fullerenes, nanodiamonds, carbon nanotubes, graphene, graphene oxide and reduced graphene oxide) employed in the preparation of hydrogels are described as well as carbon-based nanocomposite hydrogels (CBNHs) with versatility (conductivity, antibacterial, injectable and self-healing, anti-inflammatory and antioxidant properties, substance delivery, stimulus response and real-time monitoring). Moreover, applications of CBNHs in treating different chronic wounds are concretely discussed. This review may provide some new inspirations for the future development of CBNHs in wound care and tissue engineering. Full article

Scaffolds play a crucial role in tissue engineering as regenerative templates. Fabricating scaffolds with good biocompatibility and appropriate mechanical properties remains a major challenge in this field. This study proposes a method for preparing multi-material scaffolds, enabling the 3D printing of collagen and thermoplastic elastomers at room temperature. Addressing the previous challenges such as the poor printability of pure collagen and the difficulty of maintaining structural integrity during multilayer printing, this research improved the printability of collagen by optimizing its concentration and pH value and completed the large-span printing of thermoplastic elastomer using a precise temperature-control system. The developed hybrid scaffold has an interconnected porous structure, which can support the adhesion and proliferation of fibroblasts. The scaffolds were further treated with different post-treatment methods, and it was proven that the neutralized and cross-linked collagen scaffold, which has both nano-fibers and a certain rigidity, can better support the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). The research results show that the collagen thermoplastic elastomer hybrid scaffold has significant clinical application potential in soft tissue and hard tissue regeneration, providing a versatile solution to meet the diverse needs of tissue engineering. Full article

Advances in drug delivery systems adapted with regenerative medicine have transformed healthcare by introducing innovative strategies to treat (and repair in many instances) disease-impacted regions of the human body. This review provides a comprehensive analysis of the latest developments and challenges in integrating drug delivery technologies with regenerative medicine. Recent advances in drug delivery technologies, including the design of biomaterials, localized delivery techniques, and controlled release systems guided by mathematical models, are explored to illustrate their role in enhancing therapeutic precision and efficacy. Additionally, regenerative medicine approaches are analyzed, with a focus on extracellular matrix components, stem cell-based therapies, and emerging strategies for organ regeneration in both soft and hard tissue and in vitro model engineering. In particular, the review also discusses the applications of cellular components, including stem cells, immune cells, endothelial cells, and specialized cells such as chondrocytes and osteoblasts, and highlights advancements in cell delivery methods and cell–cell interaction modulation. In addition, future directions and pivotal trends emphasizing the importance of interdisciplinary collaboration and cutting-edge innovations are provided to address successful therapeutic outcomes in regenerative medicine. Full article

Modern tissue engineering requires not only degradable materials promoting cell growth and differentiation, but also vascularization of the engineered tissue. Porous polylactide/polycaprolactone (PLA/PCL, ratio 3/5) foam scaffolds were prepared by a combined porogen leaching and freeze-drying technique using NaCl (crystal size 250–500 µm) and a water-soluble cellulose derivative (Klucel^TM E; 10–100% w/w relative to the total PLA/PCL concentration) as porogens. Scanning electron microscopy, micro-CT, and Brunauer–Emmett–Teller analysis showed that all scaffolds contained a trimodal range of pore sizes, i.e., macropores (average diameter 298–539 μm), micropores (100 nm to 10 μm), and nanopores (mostly around 3.0 nm). All scaffolds had an open porosity of about 90%, and the pores were interconnected. The size of the macropores and the nanoporosity were higher in the scaffolds prepared with Klucel. Nanoporosity increased water uptake by the scaffolds, while macroporosity promoted cell ingrowth, which was most evident in scaffolds prepared with 25% Klucel. Human adipose-derived stem cells co-cultured with endothelial cells formed pre-vascular structures in the scaffolds, which was further enhanced in a dynamic cell culture system. The scaffolds are promising for the engineering of pre-vascularized soft tissues (relatively pliable 10% Klucel scaffolds) and hard tissues (mechanically stronger 25% and 50% Klucel scaffolds). Full article

The primary challenges in the tissue engineering of small-diameter artificial blood vessels include inadequate mechanical properties and insufficient anticoagulation capabilities. To address these challenges, urea-pyrimidone (Upy)-based polyurethane elastomers (PIIU-B) were synthesized by incorporating quadruple hydrogen bonding within the polymer backbone. The synthesis process employed poly(L-lactide-ε-caprolactone) (PLCL) as the soft segment, while di-(isophorone diisocyanate)-Ureido pyrimidinone (IUI) and isophorone diisocyanate (IPDI) were utilized as the hard segment. The resulting PIIU-B small-diameter artificial blood vessel with a diameter of 4 mm was fabricated using the electrospinning technique, achieving an optimized IUI/IPDI composition ratio of 1:1. Enhanced by multiple hydrogen bonds, the vessels exhibited a robust elastic modulus of 12.45 MPa, an extracellular matrix (ECM)-mimetic nanofiber morphology, and a high porosity of 41.31%. Subsequently, the PIIU-B vessel underwent dual-functionalization with low-molecular-weight heparin and gelatin via ultraviolet (UV) crosslinking (designated as PIIU-B@LHep/Gel), which conferred superior biocompatibility and exceptional anticoagulation properties. The study revealed improved anti-platelet adhesion characteristics as well as a prolonged activated partial thromboplastin time (APTT) of 157.2 s and thrombin time (TT) of 64.2 s in vitro. Following a seven-day subcutaneous implantation, the PIIU-B@LHep/Gel vessel exhibited excellent biocompatibility, evidenced by complete integration with the surrounding peri-implant tissue, significant cell infiltration, and collagen formation in vivo. Consequently, polyurethane-based artificial blood vessels, reinforced by multiple hydrogen bonds and dual-functionalized with heparin and gelatin, present as promising candidates for vascular tissue engineering. Full article

Inspiration from nature is a promising tool for the design of new polymeric biomaterials, especially for frontier technological areas such as tissue engineering. In tissue engineering, polyurethane-based implants have gained considerable attention, as they are materials that can be designed to meet the requirements imposed by their final applications. The choice of their building blocks (which are used in the synthesis as macrodiols, diisocyanates, and chain extenders) can be implemented to obtain biomimetic structures that can mimic native tissue in terms of mechanical, morphological, and surface properties. In recent years, due to their excellent chemical stability, biocompatibility, and low cytotoxicity, polyurethanes have been widely used in biomedical applications. Biomimetic materials, with their inherent nature of mimicking natural materials, are possible thanks to recent advances in manufacturing technology. The aim of this review is to provide a critical overview of relevant promising studies on polyurethane scaffolds, including those based on non-isocyanate polyurethanes, for the regeneration of selected soft (cardiac muscle, blood vessels, skeletal muscle) and hard (bone tissue) tissues. Full article

Repairing hard tissues, such as bones, remains a significant challenge, especially in adverse clinical conditions. Calcium hydroxyapatite (CaHA), a calcium phosphate (CaP), has structural and chemical characteristics similar to the mineral structure of human bones and teeth, offering bioactivity and biocompatibility properties. Photobiomodulation (PBM) uses light to reduce inflammation and accelerate tissue healing. This systematic review analyzes the combination of CaHA and PBM from 25 studies extracted from the PubMed, Web of Science, and ScienceDirect databases, using the keywords “hydroxyapatite AND photobiomodulation”, “calcium hydroxyapatite AND photobiomodulation”, and “low-level laser therapy AND calcium phosphate.” All studies focused on bone regeneration, with no mention of soft tissue applications. The most commonly used calcium-based material was biphasic calcium phosphate (76%), a combination of CaHA and β-tricalcium phosphate, while 16% of the studies did not specify the brand or product used. With regard to PBM, the most commonly used wavelengths (48% of cases, with a tie of 24% for each) were infrared lasers at 808 nm and 780 nm, with 20% of studies not mentioning the brand or manufacturer. The results underscore the predominant focus on bone regeneration, highlighting the need for further investigations into soft tissue applications and the establishment of standardized protocols. The combination of CaHA and PBM shows promise in regenerative medicine and dentistry, although more research is needed to expand its experimental and clinical use. Full article