Search Results (622)

In this study, a shape-changeable 3D scaffold with photothermal effects was developed to address the clinical challenges of complex bone defects. The multifunctional construct was fabricated via in situ polymerization combined with a gas foaming technique, creating hierarchical porous architectures that mimic the native bone extracellular matrix. By incorporating polydopamine (PDA)-modified amorphous calcium phosphate (CA) into poly(propylene glycol) (PPG)- and poly(ԑ-caprolactone) (PCL)-based polyurethane (PU). The obtained scaffolds achieved osteoinductive potential for bone tissue engineering. The surface PDA modification of CA enabled efficient photothermal shape conversion under near-infrared (NIR) irradiation, facilitating non-invasive remote control of localized hyperthermia. The optimized scaffolds exhibited interconnected porosity (approximately 70%) with osteoconductive pore channels (200–500 μm), resulting in good osteoinduction in cell culture, and precise shape-memory recovery at physiological temperatures (~40 °C) under NIR for minimally invasive delivery. The synergistic effect of osteogenesis promotion and photothermal transition demonstrated this programmable scaffold as a promising solution for integrated minimally invasive bone repair and defect reconstruction. Full article

The combination of scaffold materials and bioactive factors is a promising strategy for promoting bone defect repair in tissue engineering. Previous studies have shown that osteoglycin (OGN) is highly expressed in the bone repair process using deer antler as an animal model of bone defects. It suggests that OGN may be a key active component involved in the bone repair process. The aim of this study was to investigate whether deer OGN (dOGN) could effectively promote bone regeneration. We successfully expressed dOGN using the E. coli pET30a system and evaluated its biological activity through cell proliferation and migration assays. At a concentration of 5 μg/mL, dOGN significantly promoted cell proliferation and migration. We then incorporated dOGN onto decellularized antler cancellous bone (DACB) scaffolds and assessed their osteogenic potential both in vitro and in vivo. The results indicated that dOGN loading enhanced cell proliferation, adhesion, and osteogenic activity. In vivo experiments confirmed that the dOGN-DACB scaffold significantly improved bone regeneration compared to DACB alone. This study demonstrates that dOGN-loaded DACB scaffolds hold great potential for clinical applications in treating critical-sized bone defects by mimicking the rapid regenerative properties of deer antlers. Full article

Background: Mesenchymal stem cells (MSCs), multipotent and immune-regulatory cells derived from tissues such as bone marrow, dental pulp, and periodontal ligament, emerged as promising agents in regenerative dentistry. Their clinical applications include endodontic tissue regeneration, periodontal healing, and alveolar bone repair, addressing critical challenges in dental tissue restoration. Methods: A systematic review was conducted following PRISMA guidelines and registered in PROSPERO. We searched PubMed, Scopus, and Web of Science databases for open-access, English-language clinical trials and observational studies published from 2015 to 2025. Studies focusing on the application of MSCs in dental tissue regeneration were included based on predefined eligibility criteria. Results: Out of 2400 initial records, 13 studies met the inclusion criteria after screening and eligibility assessment. Most studies investigated MSCs derived from dental pulp and periodontal ligament for regenerating periodontal tissues and alveolar bone defects. The majority reported improved clinical outcomes; however, variations in MSC sources, delivery methods, sample sizes, and follow-up periods introduced methodological heterogeneity. Conclusions: MSCs show significant potential in enhancing bone and periodontal regeneration in dental practice. Nonetheless, the current evidence is limited by small sample sizes, short follow-up, and inconsistent methodologies. Future large-scale, standardized clinical trials are required to validate MSC-based regenerative therapies and optimize treatment protocols. Full article

Bioactive glass materials have been used for decades in orthopedic surgery, traumatology, and oral and maxillofacial surgery to repair bone defects. This study aimed to evaluate in vitro the survival and proliferation of MG63 human osteosarcoma-derived cells on S53P4 bioactive glass (BonAlive^® granules). Microscopic visualization was performed to directly observe the interactions between the cells and the material. Osteoblast-like cells were examined on non-adherent test plates, on tissue culture (TC)-treated plates and on the surface of the bioglass to assess the differences. Cell survival and proliferation were monitored using a CCK-8 optical density assay. Comparing the mean OD of MG63 cells in MEM on TC-treated plates with cells on BG, we detected a significant difference (p < 0.05), over each time of observation. The sustained cell proliferation confirmed the non-cytotoxic property of the bioglass, as the cell number increased continuously at 48, 72, 96, and 168 h and even did not plateau after 168 h. Since the properties of bioglasses can vary significantly depending on their composition and environment, a thorough characterization of their biocompatibility is crucial to ensure their effective and appropriate application—for example, during hip and knee prosthesis insertion. Full article

This study evaluated the bone regeneration effect and mechanical properties of “Sticky bone”, a mixture of platelet-rich fibrin (PRF) and synthetic bone grafts (SBGs), in the repair of large femoral bone defects in rabbits. Eighteen New Zealand white rabbits were included and randomly divided into a Sticky bone group and an SBG alone group. Bone graft samples were collected and analyzed at 4, 8, and 12 weeks after surgery. Micro- computed tomography (CT) analysis showed that the amount of the Sticky bone group in the grayscale ranges of 255–140 (highly mineralized tissue or unabsorbed bone powder) and 140–90 (representing new cancellous bone) was higher than that of the SBG group at each time point and decreased with the number of weeks. The compression strength test showed that the average compression strength of the Sticky bone group reached 5.17 MPa at the 12th week, which was 1.62 times that of the intact bone (3.19 MPa) and was significantly better than that of the SBG group (about 4.12 MPa). This study also confirmed for the first time that the use of a new polyethylene terephthalate (PET) blood collection tube to prepare PRF can stably release key growth factors such as platelet-derived growth factor-BB (PDGF-BB) and vascular endothelial growth factor (VEGF), which are conducive to early bone vascularization and cell proliferation. In summary, Sticky bone has the potential to promote bone formation, enhance tissue integration and mechanical stability, and can be used as an effective alternative material for repairing large-scale bone defects in clinical practice in the future. Full article

Background and Objectives: Although the use of allografts in revision anterior cruciate ligament reconstruction is associated with theoretical advantages, it has historically led to poorer clinical results and lower survival rates. However, the heterogeneity of the available literature makes it difficult to elucidate the effectiveness of allographs, as most of the studies published do not make any reference to some of the key aspects related to the processing of the allograft employed. The present study analyzed the clinical results and the survival of allografts in patients undergoing revision anterior cruciate ligament reconstruction with a well-characterized, single type of allograft. Materials and Methods: This was a retrospective observational study analyzing a series of patients undergoing revision anterior cruciate ligament reconstruction with an Achilles tendon allograft with a bone block (FlexiGraft, LifeNet Health), subjected to low-dose irradiation at dry ice temperatures. Preoperative and follow-up clinical variables (IKDC, pain, hop test, and YBT scores) were recorded. Survival was analyzed using the Kaplan–Meier methodology. Results: A total of 39 patients (34 male, 5 female) were included in the study. The mean patient age was 37.3 years and mean postoperative follow-up was 78.7 months. Forty-one percent of patients were competitive athletes, and all of the patients in the sample exhibited preoperative instability. The mean allograft thickness was 9.2 mm. During surgery, 51.3% of patients required meniscus repair and 20.5% had to be treated for chondral defects. At the last follow-up visit, 92.3% of the subjects presented with IKDC grade A and 7.7% with IKDC grade B. The mean subjective IKDC score was 0.79 and mean pain intensity was 1.15 according to the VAS scale. Limb symmetry, as measured by the various hop tests and the Y balance test, were within the safety range, with 74.4% of patients succeeding in returning to their previous level of sport. Ten-year survival was estimated at 97.4%. Conclusions: Allografts obtained and processed following the current regulations governing patient selection and graft harvesting, which are additionally processed without recourse to chemical procedures and sterilized at less than 2 MRad in dry ice conditions, represent an effective and safe alternative in revision anterior cruciate ligament reconstruction. Full article

We present a narrative review focusing on the therapeutic potential of mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) in regenerating bone defects, particularly those resulting from surgical treatment of malignant bone and soft tissue tumors. These large bone defects pose significant challenges for reconstruction and functional recovery, highlighting the need for innovative regenerative strategies. Background: MSCs, which can differentiate into various cell types, are known for their immunosuppressive properties and ability to promote tissue repair. MSC-EVs, rich in bioactive molecules like microRNAs and proteins, play a crucial role in bone regeneration by mediating intercellular communication and modulating inflammation. Methods: This narrative review compiles data from various studies, including systematic reviews and individual research, focusing on the application of MSC-EVs in bone defect treatment. It examines the characteristics, mechanisms of action, and therapeutic effects of MSC-EVs, as well as the microRNAs involved in bone regeneration. Results: The findings indicate that MSC-EVs can enhance both osteogenesis and angiogenesis, highlighting their potential as promising candidates for clinical applications in bone defects. However, many mechanisms remain unclear; therefore, further investigation is needed. Conclusions: The review emphasizes the potential of MSC-EVs in improving patient outcomes for severe bone defects. It also highlights future challenges, including formulation, standardization, safety, and delivery methods, particularly in conjunction with biomaterials. Overall, MSC-EVs represent a significant advancement in regenerative medicine for bone defects. Full article

Thermosensitive hydrogels undergo reversible sol-gel phase transitions in response to changes in temperature. Owing to their excellent biocompatibility, mild reaction conditions, and controllable gelation properties, these hydrogels represent a promising class of biomaterials suitable for minimally invasive treatment systems in diverse biomedical applications. This review systematically summarizes the gelation mechanisms of thermosensitive hydrogels and optimization strategies to enhance their performance for broader application requirements. In particular, we highlight recent advances in injectable thermosensitive hydrogels as a carrier within stem cells, bioactive substances, and drug delivery for treating various tissue defects and diseases involving bone, cartilage, and other tissues. Furthermore, we propose challenges and directions for the future development of thermosensitive hydrogels. These insights provide new ideas for researchers to explore novel thermosensitive hydrogels for tissue repair and disease treatment. Full article

Although publications have documented the osteo-inductive effects of various bioactive materials on tissue sections, the associated morphologic patterns of tissue remodeling pathways at the cellular level have not been detailed. Therefore, we present a comparative histopathological follow-up evaluation of bone defect repair mediated by silica aerogels and methacrylate hydrogels over a 6-month period, which is the widely accepted time course for complete resolution. Time-dependent microscopic analysis was conducted using the “critical size model”. In untreated rat calvaria bone defects (control), re-ossification exclusively started at the lateral regions from the edges of the remaining bone. At the 6th month, only a few new bones were formed, which were independent of the lateral ossification. The overall ossification resulted in a 57% osseous encroachment of the defect. In contrast, aerogels (AE), hydrogels (H), and their β-tricalcium-phosphate (βTCP)-containing counterparts, which were used to fill the bone defects, characteristically induced rapid early ossification starting from the 1st month. This was accompanied by fibrous granulomatous inflammation with multinucleated giant macrophages, which persisted in decreasing intensity throughout the observational time. In addition to lateral ossification, multiple and intense intralesional osseous foci developed as early as the 1st month, and grew progressively thereafter, reflecting the osteo-inductive effects of all compounds. However, both βTCP-containing bone substituents generated larger amounts and more mature new bones inside the defects. Nevertheless, only 72.8–76.9% of the bone defects treated with AE and H and 80.5–82.9% of those treated with βTCP-containing counterparts were re-ossified by the 6th month. Remarkably, by this time, some intra-osseous hydrogels were found, and traces of silica from AE were still detectable, indicating these as the causative agents for the persistent osseous–fibrous granulomatous inflammation. When silica or methacrylate-based bone substituents are used, chronic ossifying fibrous granulomatous inflammation develops. Although 100% re-ossification takes more than 6 months, by this time, the degree of osteo-fibrous solidification provides functionally well-suited bone repair. Full article

This study aimed to evaluate the effectiveness of different rehabilitation protocols following osteochondral autograft transplantation (OAT) in patients with focal osteochondral defects of the femoral condyle, using the MOCART 2.0 knee score as a primary imaging outcome. Twenty-nine patients were divided into three groups: Group 1 (n = 9) received OAT with bone marrow aspirate concentrate (BMAC) and a 12-week two-phase rehabilitation program; Group 2 (n = 11) received OAT with a 12-week program without BMAC; and Group 3 (n = 9) received OAT with a shortened 6-week program. At the 12-month follow-up, Group 1 demonstrated a superior cartilage repair quality, with the highest mean MOCART 2.0 score (96.1), compared to Group 2 (80.2) and Group 3 (71.7). Notably, complete defect filling was observed in five patients in Group 1 versus four in Group 2 and only one in Group 3. The integration and surface integrity were also better preserved in Group 1. The addition of BMAC and an extended, progressive rehabilitation protocol significantly enhanced the morphological cartilage repair parameters. These results suggest that a biologically enhanced and prolonged recovery plan may offer a greater structural restoration of cartilage after OAT than conventional or accelerated protocols. Full article

Bone marrow stimulation is a treatment for articular cartilage injuries that promotes cartilage repair by inducing the migration and accumulation of mesenchymal stem cells (MSCs), but often results in fibrocartilage with limited durability. This study aimed to investigate the effect of hypoxic conditions on cartilage repair using a rat osteochondral defect model. Osteochondral defects (1.0 mm in diameter) were created in the femoral trochlear groove, and rats were exposed to hypoxic conditions (12% O₂) for 4 weeks postoperatively. Histological analysis was performed, and protein expression of hypoxia-inducible factor-1α (HIF-1α) and SRY-box transcription factor 9 (SOX9) in the repair tissue was evaluated after 1 week. As a result, after 1 week, protein expression of HIF-1α and SOX9 in the Hypoxia group was significantly increased compared to the Normoxia group. After 4 weeks, the Hypoxia group exhibited a hyaline cartilage-like tissue structure with a significantly lower Modified Wakitani score compared to the Normoxia group. Furthermore, after 4 weeks, the inhibition of HIF-1α suppressed cartilage repair. These findings suggest that hypoxic conditions promote SOX9 expression via HIF-1α during the early phase of MSC chondrogenic differentiation and promote the formation of hyaline cartilage-like repair tissue. In conclusion, bone marrow stimulation under hypoxic conditions may enhance the repair effect on articular cartilage injuries. Full article

Hydroxyapatite (HAP) is the most widely accepted biomaterial for repairing bone tissue defects, demonstrating excellent biocompatibility and bioactivity that promote new bone formation. Zirconia (ZrO₂), known for its strength and fracture toughness, is commonly used to reinforce ceramics. In this study, magnesium oxide (MgO) served as a stabilizer for zirconia, resulting in magnesia partially stabilized zirconia (Mg-PSZ). Both Mg-PSZ and HAP were synthesized via coprecipitation and mixed in specific ratios to create composites through a ceramic method involving mixing, compaction, and sintering at 1100 °C. The samples were characterized using techniques such as X-ray powder diffraction (XRPD), Fourier-transform infrared spectroscopy (FTIR), and scanning electron microscopy/energy-dispersive X-ray spectroscopy (SEM/EDS). Structural analyses confirmed the presence of both monoclinic and tetragonal zirconia phases. Besides, the increased wt.% HAP in the composites produced distinct peaks for hexagonal HAP. Crystallite sizes ranged from 27.45 nm to 31.5 nm, and surface morphology was homogeneous with small pores. Elements such as calcium, phosphorus, magnesium, zirconium, and oxygen were detected in all samples. This research also examined microhardness changes in the materials. The findings revealed enhancement in microhardness for the biocomposite with higher zirconia content, 90Mg-PSZ/10HAP sample, with the smallest average pore size, highlighting its potential for biomedical applications. 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

Critical-sized bone defects (CSBDs) are injuries that exceed the body’s natural capacity for repair and require external intervention. These defects are particularly challenging in the mandible, often resulting from trauma, tumor resection, or implant-related complications. Effective treatment involves scaffold designs that support vascularization, bone formation, and sufficient mechanical strength. This systematic review aims to assess whether ceramic-based scaffold properties, including porosity, pore size, and macroscopic characteristics, improve vascularization, bone formation, and the mechanical properties in the treatment of CSBDs in large animal models. A search of databases (PubMed, Embase, and Web of Science) identified 11 in vivo studies involving CSBDs (>2 cm), ceramic scaffolds, and histological analysis. Findings indicate that scaffolds with porosity exceeding 50% yield optimal outcomes by striking a balance between cell infiltration and mechanical stability. Pore sizes ranging from 300 μm to 700 μm are ideal for vascularization and bone ingrowth. Three-dimensional (3D) printing shows promise in creating scaffolds with precise and reproducible features. However, the studies varied significantly in their methodologies and outcomes, with no consensus on the optimal scaffold properties for mandibular CSBDs. Scaffold porosity and pore size play key roles in promoting vascularization and bone regeneration. Various animal models reinforce this finding, suggesting that scaffold architecture is crucial for biological integration and functional outcomes. This review highlights the importance of standardized research protocols and clear design criteria in enhancing the success of bone regeneration. Future research should investigate emerging biomaterials and new scaffold technologies to overcome current limitations in clinical applications. Full article

Cartilage and bone defects as well as osteoarthritis are prevalent worldwide, affecting individuals across all age groups, from young, active populations to older adults. The standard protocol in cartilage regeneration involves knee replacement surgery through the implantation of an endoprosthesis. Current clinical protocols involving cell-based therapies are associated with limitations, including the lack of functional cartilage-like tissue and dedifferentiation of chondrocyte, particularly during monoculture. Similarly, in bone regeneration, the “gold standard” is the use of bone auto- or allografts, which are associated with immunological rejection, inadequate vascularization, and limited osteogenesis. To overcome these limitations, various co-culture techniques have been introduced as promising strategies for cartilage and bone tissue regeneration. These systems aim to mimic native microenvironments by promoting interactions between chondrocytes and mesenchymal stromal cells (MSCs) in cartilage repair and between osteogenic and angiogenic cells in bone regeneration. This paper introduces different co-culture systems focusing on in vitro crosstalk between MSCs derived from various sources and other somatic cell populations in cartilage and bone regeneration. Full article