Search Results (109)

This study aimed to develop and characterize novel 3D-printed chitosan methacryloyl (CSMA) hydrogel-functionalized nano-hydroxyapatite/polycaprolactone (nHA/PCL) scaffolds for controlled release of bone marrow mesenchymal stem cell-exosomes (BMSC-Exos), with the objective of enhancing osteogenic and angiogenic capabilities in vitro. We fabricated a biomimetic, highly porous scaffold composed of nHA/PCL using high-temperature fused deposition modeling. An interfacial bioactive layer was formed via ultraviolet-induced crosslinking of CSMA hydrogel on the scaffold and loaded bone marrow mesenchymal stem cell-exosomes. We characterized the composite scaffold to evaluate its physicochemical properties, cytocompatibility, cell migration ability, osteogenic capacity, and angiogenic capacity. The 3D-printed 20%nHA/PCL scaffold has a porosity of approximately 75%, with its surface containing four elements: carbon, oxygen, calcium, and phosphorus. The compressive strength is (13.76 ± 1.33) MPa. The CSMA hydrogel exhibits good injectability and degrades slowly over time. Exosomes with a negative charge are released slowly within the extracellular matrix hydrogel. The contact angle of the scaffold material is below 90 degrees, and the hemolysis rate is below 5%. In vitro assays demonstrated that the nHA/PCL-CSMA-Exos composite exhibited excellent biocompatibility, markedly enhanced cell proliferation and migration, and robust pro-angiogenic and osteogenic activity. The fabricated nHA/PCL-CSMA-Exos composite scaffolds demonstrated excellent physicochemical properties, biocompatibility, and cell migration ability, promoting angiogenesis, bone tissue formation and mineralization. Full article

Polymer-based bioactive composites are one of the most rapidly advancing areas in contemporary regenerative medicine. This review aims to identify major trends and knowledge gaps in the development of bioactive polymer composites and examine their translational relevance from a materials design perspective, with a specific focus on synthetic thermoplastic polymer matrices suitable for load-bearing bone scaffold applications and filament-based additive manufacturing. A total of 546 publications spanning 2016–2025 were screened, with 106 selected according to predefined relevance criteria. Bibliometric and content analyses were performed to delineate the primary research trajectories of bioactive composite materials. The results revealed that the majority of studies focused on composites comprising synthetic aliphatic polyesters, primarily polylactic acid (PLA) or polycaprolactone (PCL), reinforced with hydroxyapatite (HA) or bioactive glass (BG), which confer osteoconductivity but rarely achieve multifunctionality. Antimicrobial agents, ion-releasing components, and naturally derived bioactive molecules—associated with biointeractive functionalities and reported effects related to osteogenesis, angiogenesis, and immune modulation—are significantly underrepresented. Fewer than 20% of the investigated studies include in vivo validation, underscoring considerable scope for further preclinical and translational research. This work consolidates current trends in synthetic bioactive polymer composite design and identifies critical directions for future research. The findings of this review provide a structured framework to support the selection of composite fabrication and modification strategies, functional additives, and targeted biological functionalities for next-generation, load-bearing bone tissue engineering materials. Full article

Injectable biostimulatory agents such as poly-L-lactic acid (PLLA), polycaprolactone (PCL), and calcium hydroxyapatite (CaHA) have emerged as key tools in regenerative aesthetics due to their ability to stimulate adipogenesis and adipocyte metabolic activity, enhance collagen production, and improve dermal quality. This review aimed to provide an updated synthesis of the role of these agents in adipocyte stimulation, focusing on their mechanisms of action, clinical efficacy, and therapeutic applications. A comprehensive search of the MEDLINE, PubMed, and Ovid databases was conducted for studies published from 2018 onward, including in vitro and in vivo experiments, randomized controlled trials, and observational studies, which were evaluated according to the Oxford Centre for Evidence-Based Medicine hierarchy. The findings demonstrated that PCL promotes adipose-derived stem cell differentiation and extracellular matrix remodeling, while PLLA exhibits dual effects on collagen synthesis and adipocyte stimulation, with clinical trials such as the SPLASH study confirming significant improvements in dermal thickness and adipogenesis. CaHA provided immediate volumizing benefits with long-term tissue regeneration, and innovative approaches including combination therapies and novel injection protocols expanded clinical applications. Overall, PLLA, PCL, and CaHA represent effective and versatile biostimulatory agents that support natural and durable outcomes in aesthetic practice. Nevertheless, the absence of large-scale trials and standardized protocols highlights the need for further research to optimize safety, efficacy, and long-term treatment strategies. Full article

The increasing demand for novel tissue engineering (TE) applications in bone tissue regeneration underscores the importance of exploring advanced manufacturing techniques and biomaterials for personalised treatment approaches. Three-dimensional printing (3DP) technology facilitates the development of implantable devices with intricate geometries, enabling patient-specific therapeutic solutions. Although Fused Filament Fabrication (FFF) and Direct Ink Writing (DIW) are widely utilised for fabricating bone-like implants, the need for multiple processing steps often prolongs the overall production time. In this study, a single-step melt-extrusion 3DP technique was performed to develop multi-material scaffolds including bioceramics, hydroxyapatite (HA), and β-tricalcium phosphate (TCP) in both their bioactive and calcined forms at 10% and 20% w/w, within polycaprolactone (PCL) matrices. Printing parameters were optimised, and physicochemical properties of all biomaterials and final forms were evaluated. Thermal degradation and surface morphology analyses assessed the consistency and distribution of the ceramics across the different formulations. The tensile testing of the scaffolds defined the impact of each ceramic type and wt% on scaffold flexibility performance, while in vitro cell studies determined the cytocompatibility efficiency. Hence, all 3D-printed PCL–ceramic composite scaffolds achieved structural integrity and physicochemical and thermal stability. The mechanical profile of extruded samples was relevant to the ceramic consistency, providing valuable insights for further mechanotransduction investigations. Notably, all materials showed high cell viability and proliferation, indicating strong biocompatibility. Therefore, this additive manufacturing (AM) process is a precise and fast approach for developing biomaterial-based scaffolds, with potential applications in surgical restoration and support of segmental bone defects. Full article

A varied family of polyphenolic chemicals, flavonoids, are becoming more and more important in bone tissue engineering because of their osteogenic, anti-inflammatory, and antioxidant effects. Recent developments incorporating flavonoids into different biomaterial platforms to improve bone regeneration are emphasized in this study. Osteocalcin (OCN) expression was 2.1-fold greater in scaffolds loaded with flavonoids—such as those made of polycaprolactone (PCL)—greatly increasing human mesenchymal stem cell (hMSC) proliferation and mineralization. Comparably, a threefold increase in calcium deposition indicates increased mineralization when hydroxyapatite (HA) was functionalized with flavonoids such as quercetin. These HA scaffolds with flavonoids also showed a 45% decrease in osteoclast activity, therefore promoting balanced bone remodeling. Concurrent with flavonoids like EGCG and quercetin, chitosan-based scaffolds encouraged osteogenic differentiation with increases in osteogenic markers like osteopontin (OPN) and alkaline phosphatase (ALP) expression by up to 82%. These scaffolds also showed 82% bone defect repair after six weeks in vivo, suggesting their promise in rapid bone regeneration. With an increase of up to 32% in the bone volume-to-total volume ratio (BV/TV) and 28% greater bone–implant contact (BIC), flavonoid coatings on titanium implants enhanced osteointegration in implantology. Displaying successful osteogenesis and immunomodulation, the addition of flavonoids into metal–organic frameworks (MOFs) and injectable hydrogels demonstrated a 72% increase in new bone formation in vivo. Though further research is required to confirm long-term clinical effectiveness, these findings show the great promise of flavonoid-functionalized biomaterials in bone regeneration. Full article

Nanoscale amorphous calcium phosphate (ACP) exhibits superior bioactivity, degradability, and osteoblast adhesion compared to hydroxyapatite (HAp), making it a promising bioactive ceramic material for bone regeneration applications. This study explores the integration of ACP as a bioactive additive in polylactic acid/polycaprolactone (PLA/PCL) composites. Nanoscale ACP powder was synthesized through low-temperature wet chemical methods without additional reagents. The composite, consisting of 10 wt.% ACP, 80 wt.% PLA, and 20 wt.% PCL, achieved optimal tensile strength (>12 MPa) and elongation (>0.1%). Utilizing the Taguchi experimental design, the microinjection molding parameters were optimized, and they are a material temperature of 190 °C, an injection speed of 50 mm/s, and a holding pressure speed of 30 mm/s. Variance analysis identified the injection speed to be the most significant factor, contributing 50.73% to the overall effect. Immersing ACP in simulated body fluid (SBF) for six hours reduced its calcium ion concentration by 28%, with this concentration stabilizing thereafter. Biocompatibility was confirmed through an MTT assay with NIH-3T3 cells, demonstrating the PLA/PCL/ACP composite’s compatibility. Bone differentiation and mineralization tests showed the enhanced performance of both ACP and the composite material. Degradation tests indicated an initial 0.29% weight increase in the first week, followed by a 2% reduction by the fifth week. These results underscore the PLA/PCL/ACP composite’s excellent mechanical properties, biocompatibility, and suitability for injection molding, positioning it as a strong candidate for biodegradable bone screw applications. Full article

In this study, the microinjection molding technology was adopted to prepare polylactic acid (PLA)/polycaprolactone (PCL)/bioactive glass (BG) composites with varying BG contents for biomedical applications. The various measurement techniques, including scanning electronic microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy, the water contact angle (WCA) test, the mechanical test, and in vitro biological evaluations, were applied to characterize the above interesting biocomposites. The experimental results show that the extremely strong shear force field generated during the microinjection molding process could induce the in situ formation of micron PCL dispersed phase fibril structures and strongly promote the homogeneous dispersion of micron BG filler particles in the PLA/PCL polymer matrix, which therefore leads to a significant improvement in the specific mechanical property of the PLA/PCL/BG composite. For example, with BG fillers content increasing to 10 wt%, the Young’s modulus of the above obtained PLA/PCL/BG composite could reach 2122.9 MPa, which is 1.47 times higher than that of the unfilled PLA/PCL blend material. In addition, it is also found that under the simulated body fluid (SBF) environment, the incorporated BG fillers in the PLA/PCL polymer matrix could be effectively transformed into hydroxyapatite (HA) components on the treated sample surface, thus being greatly advantageous to enhancing the material’s in vitro bioactivity. Obviously, the microinjection molded PLA/PCL/BG biocomposites could exhibit excellent comprehensive performance, revealing that the microinjection molding processing method could hold great potential in industrialization applications of the resulting biodegradable biomedical materials. Full article

The limitations of traditional, autologous bone grafts, such as the scarcity of donor material and the risks of secondary surgical trauma, have spurred the development of alternatives for the repair of large bone defects. Bionic bone scaffolds fabricated via fused deposition modeling (FDM)—a three-dimensional (3D) printing technique—are considered promising. While gyroid-structured scaffolds mimic the complex micro-architecture of cancellous bone, their application in FDM 3D printing remains understudied. Furthermore, no consensus has been reached on the ideal pore size for gyroid scaffolds, which is influenced by the infill density. In this study, we fabricated five groups of polycaprolactone/hydroxyapatite (PCL/HA) scaffolds with different infill densities (40%, 45%, 50%, 55%, and 60%) using a solvent-free filament preparation method. Scanning electron microscopy (SEM) observation showed that all scaffolds exhibit an interconnected porous structure. The scaffold with the 55% infill density, featuring a pore size of 465 ± 63 μm, demonstrated optimal hydrophilicity and mechanical properties comparable to natural cancellous bone. In addition, this scaffold supported cellular bridging within its pores and showed the highest alkaline phosphatase (ALP) activity and calcium salt deposition. Our findings offer novel insights into the design of gyroid-like scaffolds and their fabrication via FDM, paving the way for potential clinical applications. 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

Polycaprolactone (PCL) degradation is critical in bone tissue engineering, where scaffold degradation must align with tissue regeneration to ensure stability and integration. This study explores the effects of nanofillers, hydroxyapatite (nHA), and graphene oxide nanoscrolls (GONS) on PCL-based scaffold degradation kinetics. Both PHAP (nHA-PCL) and PGAP (nHA-GONS-PCL) scaffolds exhibited changes to relaxation-driven degradation, as indicated by adherence to the Korsmeyer–Peppas model (R² = 1.00). PHAP scaffolds showed lower activation energies (5.02–5.54 kJ/mol), promoting faster chain relaxation and degradation in amorphous regions. PGAP scaffolds, with higher activation energies (12.88–12.90 kJ/mol), displayed greater resistance to chain relaxation and slower degradation. Differential scanning calorimetry (DSC) revealed that both nanofillers disrupted the crystalline regions, shifting degradation behavior from diffusion-based to relaxation-driven mechanisms in the amorphous zones, which was also reflected by changes in crystallization temperature (Tc) and melting temperature (T_m). Additionally, PGAP scaffolds demonstrated antioxidant potential, which decreased over time as degradation progressed. These results provide a mechanistic understanding of how nanofiller-modulated degradation dynamics can be strategically leveraged to optimize scaffold performance, facilitating precise control over degradation rates and bioactivity. Full article

Using metallic/polymeric orthopedic screws causes cavities in bone trauma after the attachment of broken bones, which prolongs the healing. Yet, it remains unknown how to overcome such a challenge. The main aim of this research was to use both polymers and gels to fabricate and study a new PCL/chitosan/hydroxyapatite scaffold-like orthopedic screw for cancellous bone trauma. This screw, because of its low stiffness and its scaffold-based matrix (due to the gel part), can facilitate bone healing. Different concentrations of PCL (60–95% w/v) and chitosan (0–5% w/v) were blended according to the Response Surface Methodology using the Central Composite Design. The screws were fabricated using the freeze-drying technique. The screws were assessed mechanically, physically, and biologically (cell viability, cell attachment, DAPI, ALP staining, and Alizarin Red staining), and in vivo (a rat subcutaneous implantation model). Based on the results, screws depending on the PCL and gel content depicted different but notable mechanical behavior (10–60 MPa of compressive strength and 100–600 N force). The gel part could affect the physical properties of screws including water uptake (120%), degradation (18% after 21 days), porosities (23%), and mechanical strength (elastic modulus = 59.47 Mpa). The results also demonstrated no cytotoxicity towards MC3T3 cells (>80% cell viability) with good cell attachment, cell concentration, and mineralization (>90%) that was justified by the gel content. The results also showed good in vivo biocompatibility. To sum up, fabricated scaffold-like screws with gel content can be a good candidate for cancellous-bone-based orthopedic purposes. However, more in vitro and in vivo studies are required to optimize the PCL:gel ratio. Full article

Osteochondral (OC) tissue plays a crucial role due to its ability to connect bone and cartilage tissues. To address the complexity of structure and functionality at the bone–cartilage interface, relevant to the presence of the tidemark as a critical element at the bone–cartilage boundary, we fabricated graded scaffolds through sequential 3D printing. The scaffold’s bottom layer was based on a gelatin/oxidized alginate mixture enriched with hydroxyapatite (HAp) to create a rougher surface and larger pores to promote osteogenesis. In contrast, the upper layer was engineered to have smaller pores and aimed to promote cartilage tissue formation and mimic the physical properties of the cartilage. An electrospun ε-polycaprolactone (PCL) membrane with micrometer-range pores was incorporated between the layers to replicate the function of tidemark—a barrier to prevent vascularization of cartilage from subchondral bone tissue. In vitro cell studies confirmed the viability of the cells on the layers of the scaffolds and the ability of PCL mesh to prevent cellular migration. The fabricated scaffolds were thoroughly characterized, and their mechanical properties were compared to native OC tissue, demonstrating suitability for OC tissue engineering and graft modeling. The distance of gradient of mineral concentration was found to be 151 µm for grafts and the native OC interface. 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

Objective: The aim of this study was to systematically review the safety and effectiveness of the injectable biostimulators dermal fillers calcium hydroxyapatite (CaHA) and polycaprolactone (PCL) in facial esthetic procedures. Materials and Methods: Comprehensive electronic searches were executed across six academic databases. The primary outcome focused on safety by examining studies that reported the incidence of adverse events (AEs). The secondary outcome gauged the satisfaction of the patients and injectors by validated esthetic scales. To evaluate biases, the Joanna Briggs Institute Checklist tools were employed. Results: We included a total of 79 studies. In the quantitative assessment of the CaHA, out of 5032 injected patients, 21.8% manifested early AEs, 0.85% experienced delayed reactions, and 0.27% had severe complications. Within the PCL group, consisting of 1119 patients, 83.3% exhibited early AEs, 5.6% had delayed reactions, and none had serious complications. Regarding esthetic satisfaction outcome, both products presented favorable results, but a limited number of studies assessed these data. In the studies evaluated qualitatively, a broad array of AEs were cataloged. Conclusions: The occurrence of serious AEs associated with CaHA and PCL fillers is relatively low. Both CaHA and PCL fillers exhibit favorable safety profiles, with most AEs being transient in nature. Full article