Bone regeneration has emerged as a critical research and clinical advancement field, fueled by the growing demand for effective treatments in orthopedics and oncology. Over the past two decades, significant progress in biomaterials and surgical techniques has led to the development of novel solutions for treating bone defects, surpassing the use of traditional autologous grafts. This review aims to assess the latest approaches in bone regeneration, including autologous, allogenic, and xenogenic grafts, naturally derived biomaterials, and innovative synthetic substitutes such as bioceramics, bioactive glasses, metals, polymers, composite materials, and other specialized applications. A comprehensive literature search was conducted on PubMed, focusing on studies published between 2019 and 2024, including meta-analyses, reviews, and systematic reviews. The review evaluated a range of bone regeneration strategies, examining the clinical outcomes, materials used, surgical techniques, and the effectiveness of various approaches in treating bone defects. The search identified numerous studies, with the inclusion criteria focused on those exploring innovative bone regeneration strategies. These studies provided valuable insights into the clinical and biological outcomes of different biomaterials and graft types. Results indicated that while advancements in synthetic and naturally derived biomaterials show promising potential, challenges remain in optimizing therapeutic strategies across diverse patient populations and clinical settings. The findings emphasize the need for an integrated approach that combines scientific research, clinical practice, and technological innovation to improve bone regeneration therapies. Further research is required to establish standardized protocols and determine the optimal application of various materials and techniques to enhance patient outcomes and the quality of care.

Bone diseases represent a growing healthcare challenge due to population aging and lifestyle changes. Although bone has a natural regenerative capacity, approximately 10% of fractures fail to heal properly, requiring advanced therapeutic approaches. Bone tissue engineering (BTE) has advanced the use of osteoinductive and osteoconductive biomaterials to support bone regeneration. Among them, Bio-Oss^® Collagen, a composite of bovine hydroxyapatite and collagen, has shown excellent biocompatibility and bioactivity properties. This study analyzes the effect of Bio-Oss^® Collagen on human bone marrow-derived mesenchymal stem cells (hBMSCs), assessing its osteoinductive and immunomodulatory potential. After 7 days of culture, the biomaterial modulated the expression of key genes involved in osteogenesis and chondrogenesis, which are known for their role in bone formation and maturation. At the same time, a downregulation of genes associated with bone resorption was observed. Secretome analysis revealed a controlled release of pro-regenerative cytokines, suggesting a role of the biomaterial in modulating inflammation to promote bone regeneration. Furthermore, immunofluorescence confirmed the high expression of osteocalcin and osteopontin, which are key markers of bone mineralization. These findings indicate that Bio-Oss^® Collagen supports osteogenesis and modulates the immune response, creating a microenvironment favorable for bone regeneration.

Background: Maxillofacial bone defects present considerable challenges in oral and reconstructive surgery. While autologous bone grafts are the gold standard, their limitations, such as donor site morbidity and limited availability, have driven the search for alternative biomaterials. SmartBone^®, a xeno-hybrid graft, offers potential advantages due to its bioactivity and remodeling capacity. Methods: This analysis of a series of clinical cases, evaluated the performance of SmartBone^® in 10 patients presenting with various maxillofacial bone defects. The patient follow-up period spanned from 2017 to 2019, with a maximum duration of 30 months. Bone grafting was performed, and integration was monitored using Cone-Beam Computed Tomography at multiple timepoints. Bone density changes (ΔCT values) in selected anatomical sites were analyzed to assess graft transformation and integration. Results: SmartBone^® supported effective bone regeneration and selective remodeling in all cases. One patient required a revision procedure, after which successful integration was observed. Cellular colonization began within weeks, with complete remodeling into mature bone occurring between 6–12 months. Evidence of cortical wall resorption and reformation on the graft’s external surface confirmed this transformation. ΔCT values progressively aligned with native bone densities, indicating structural and functional integration. Conclusions: SmartBone^® demonstrates strong osteointegrative and site-specific remodeling capabilities, offering a reliable and predictable alternative for maxillofacial bone reconstruction. The study presents several limitations, including the small sample size, inter-patient variability, possible imaging artifacts due to metallic elements in Cone-Beam Computed Tomography scans and the lack of histological confirmation.

Background: The management of bone defects in pediatric oncology represents a major challenge in orthopedics, as it requires preserving both joint function and skeletal growth. Traditional reconstructive approaches, such as autografts and allografts, are limited by availability, complications, and incomplete biological integration. In this context, xeno-hybrid bone substitutes have emerged as a promising alternative. The aim of this study was to evaluate the safety and effectiveness of SmartBone^® ORTHO in the reconstruction of post-oncological bone defects in children. Methods: Twelve pediatric patients treated at the Centro Traumatologico Ortopedico (CTO) and OIRM Hospital, AOU Città della Salute e della Scienza of Turin (Italy), between 2016 and 2019 were retrospectively analyzed. Lesions included simple and aneurysmal bone cysts, non-ossifying fibroma, chondroblastoma, and other benign conditions. All patients underwent curettage followed by defect filling with SmartBone^® ORTHO. Results: At clinical and radiological follow-up, nine patients (75%) showed stable graft integration and complete functional recovery. Three patients (25%) developed local recurrence, which was managed with revision surgery and re-implantation of SmartBone^®, with all achieving stable outcomes. Radiographs demonstrated progressive increases in bone density and trabecular thickness, reaching values comparable to those of native bone within 6–12 months. Conclusions: SmartBone^® ORTHO proved to be a safe and effective biomaterial for pediatric post-oncological bone reconstruction, promoting rapid osteointegration and physiological bone remodeling without infection or intolerance.

Background: Bone regeneration is essential in oral surgery, particularly in advanced periodontal disease where teeth are no longer salvageable. Innovative biomaterials like SmartBone® combined with autologous platelet derivatives have shown promising regenerative potential. However, postoperative infections by Actinomyces israelii may compromise outcomes. Materials and Methods: A 52-year-old male with severe periodontal disease in the anterior mandible underwent extractions and grafting with SmartBone® mixed with autologous platelet derivatives using the Sticky Bone Preparation Device (SBPD). Three months post-surgery, localized inflammation occurred and was managed with antibiotics. Histopathological analysis identified A. israelii, prompting targeted antibiotic therapy. Results: Despite the infection, the graft maintained structural integrity, and the infection remained localized without fully compromising the regenerative site. After complete healing, four endosseous implants were successfully placed and restored with a fixed metal-ceramic prosthesis. Follow-ups at 8 and 30 months confirmed stable bone integration, healthy mucosa, and no recurrence. Conclusion: This case demonstrates the resilience of SmartBone® in maintaining regenerative function despite opportunistic infection. The xeno-hybrid graft and SBPD enabled successful implant-prosthetic rehabilitation. While the clinical outcome is encouraging, further microbiological studies are necessary to validate the protocol and explore any protective role of the graft material against infection.

Osteosarcoma (OS) is an aggressive primary bone tumour with high metastatic potential. Current treatments including surgery and chemotherapy are limited by side effects and chemoresistance, underscoring the need for novel therapies. This study aimed to investigate the antitumor potential of resveratrol (RSV), a natural polyphenol, as a novel treatment for OS. The effects of RSV were evaluated in two osteosarcoma cell lines (SAOS‐2 and U2‐OS). A viability assay established 100 μM as the effective concentration, and hyperspectral imaging confirmed cellular uptake. Apoptosis was measured via caspase‐3/7 activity and Annexin V/PI staining, while qRT‐PCR assessed pro‐apoptotic gene expression. Flow cytometry evaluated cell‐cycle progression, and a wound‐healing assay measured migration. Gene expression analyses (qRT‐PCR) examined markers of cell adhesion, tumour progression and epithelial–mesenchymal transition. Finally, RSV's impact on the Wnt/β‐catenin pathway was determined by quantifying nuclear β‐catenin accumulation and the expression of its downstream oncogenic targets. RSV inhibited cell proliferation and induced apoptosis, increasing caspase‐3/7 activity and modulating apoptotic gene expression. RSV also caused cell cycle arrest in S‐phase. It reduced the cells' migration and altered the expression of cell adhesion and tumour progression genes, promoting a less invasive phenotype. Notably, RSV decreased nuclear β‐catenin accumulation, downregulated oncogenic targets like c‐Myc and MMPs, and upregulated E‐cadherin while reducing vimentin levels, suggesting a reversal of epithelial–mesenchymal transition. These results suggest that RSV may offer a promising therapeutic approach for osteosarcoma, modulating key pathways involved in tumour progression, metastasis and chemoresistance. Further studies are required to assess its clinical applicability.