Platelet-rich Fibrin (PRF), a second-generation blood concentrate, offers a versatile structure for bone regeneration due to its composition of fibrin, growth factors, and cytokines, with adaptations like denatured albumin-enriched with liquid PRF (Alb-PRF), showing potential for enhanced stability and growth factor dynamics. Researchers have also explored the combination of PRF with other biomaterials, aiming to create a three-dimensional framework for enhanced cell recruitment, proliferation, and differentiation in bone repair studies. This study aimed to evaluate a combination of Alb-PRF with nanostructured carbonated hydroxyapatite microspheres (Alb-ncHA-PRF), and how this association affects the release capacity of growth factors and immunomodulatory molecules, and its impact on the behavior of MG63 human osteoblast-like cells. Alb-PRF membranes were prepared and associated with nanocarboapatite (ncHA) microspheres during polymerization. MG63 cells were exposed to eluates of both membranes to assess cell viability, proliferation, mineralization, and alkaline phosphatase (ALP) activity. The ultrastructural analysis has shown that the spheres were shattered, and fragments were incorporated into both the fibrin mesh and the albumin gel of Alb-PRF. Alb-ncHA-PRF presented a reduced release of growth factors and cytokines when compared to Alb-PRF (p < 0.05). Alb-ncHA-PRF was able to stimulate osteoblast proliferation and ALP activity at lower levels than those observed by Alb-PRF and was unable to positively affect in vitro mineralization by MG63 cells. These findings indicate that the addition of ncHA spheres reduces the biological activity of Alb-PRF, impairing its initial effects on osteoblast behavior.

Medication-related osteonecrosis of the jaw (MRONJ) is considered as a severe adverse side effect of specific drugs such as anti-resorptive and anti-angiogenic medications. Evidence suggests that MRONJ is linked to invasive dental procedures, mainly dentoalveolar surgery. Several preventive strategies to minimize the risk of developing MRONJ have been investigated. However, no investigation has been attempted to evaluate the therapeutic effect of local drug-delivery technology as a preventive strategy protocol. The aim of this study is to evaluate the efficacy of hydroxyapatite-containing doxycycline (HADOX) in rats with high-risk MRONJ development. All the rats used in this study were divided into seven groups. Six groups of rats out of seven were exposed to two different doses of antiresorptive drug therapy for four weeks before undergoing an upper incisor extraction. After 28 days, all the animals were euthanized, and the bone blocks were processed for histological and histomorphometrical evaluation. The histomorphometric analysis confirmed that newly formed bone (NFB) was present in all groups, with significant differences. NFB in the HADOX group treated with zoledronic acid at 4% showed (28.38; C.I. 22.29–34.48), which represents a significant increase compared to HA (15.69; C.I. 4.89–26.48) (p = 0.02). A similar pattern was observed in the HADOX group treated with zoledronic acid 8% ZA treatment (p = 0.001). Conclusions: HADOX did not inhibit any bone repair and reduced early inflammatory response. Hence, HADOX could promote bone healing in patients undergoing antiresorptive drug therapy.

Background/Objectives: Perillyl alcohol (POH), a plant-derived compound, has demonstrated anti-tumor activity across various human cancers. Understanding the regulatory pathways through which POH exerts its effects is crucial for identifying new therapeutic opportunities and exploring potential drug repositioning strategies. Therefore, this scoping review aims to provide a comprehensive overview of the metabolic and regulatory pathways involved in the anticancer effects of POH, based on in vitro evidence. Methods: Following the PRISMA-ScR 2018 guidelines, a systematic search was conducted in the PUBMED, Web of Science, and Scopus databases. Results: A total of 39 studies were included, revealing that POH exerts its biological effects by modulating several pathways, including the regulation of cyclins, CDKs, and p21, thereby affecting cell cycle progression. It inhibits growth and promotes cell death by attenuating AKT phosphorylation, reducing PARP-1 activity, increasing caspase activity and the FAS receptor and its ligand FASL. Additionally, POH reduces ERK phosphorylation, inhibits RAS protein isoprenylation, and decreases Na/K-ATPase activity. Conclusions: In conclusion, this review delineates the key regulatory pathways responsible for mediating the biological effects of POH in cancer.

Successful biomaterials for bone tissue therapy must present different biocompatible properties, such as the ability to stimulate the migration and proliferation of osteogenic cells on the implantable surface, to increase attachment and avoid the risks of implant movement after surgery. The present work investigates the applicability of a three-dimensional (3D) model of bone cells (osteospheres) in the evaluation of osteoconductive properties of different implant surfaces. Three different titanium surface treatments were tested: machined (MA), sandblasting and acid etching (BE), and Hydroxyapatite coating by plasma spray (PSHA). The surfaces were characterized by Scanning Electron Microscopy (SEM) and atomic force microscopy (AFM), confirming that they present very distinct roughness. After seeding the osteospheres, cell–surface interactions were studied in relation to cell proliferation, migration, and spreading. The results show that BE surfaces present higher densities of cells, leaving the aggregates towards than titanium surfaces, providing more evidence of migration. The PSHA surface presented the lowest performance in all analyses. The results indicate that the 3D model allows the focal analysis of an in vitro cell/surfaces interaction of cells and surfaces. Moreover, by demonstrating the agreement with the clinical data observed in the literature, they suggest a potential use as a predictive preclinical tool for investigating osteoconductive properties of novel biomaterials for bone therapy.

Bone tissue engineering requires biomaterials capable of simultaneously supporting regeneration and preventing infection. Platelet-rich fibrin (PRF) has been widely used due to its autologous origin and growth factor release, but its rapid resorption limits its clinical applications. Albumin-PRF (Alb-PRF) membranes were developed to improve stability, and their combination with carbonated nanostructured hydroxyapatite (nCHA) may further reinforce osteoconductive properties. In this proof-of-concept study, we fabricated Alb-PRF, Alb-nCHA-PRF, and Alb-nCHA-PRF + doxycycline (DOX) membranes and characterized their physicochemical, antimicrobial, and biological performance in vitro. Membrane stability was monitored for up to 14 days; DOX incorporation and release were evaluated by autofluorescence and spectrophotometry; antimicrobial activity was assessed against E. faecalis and S. aureus; and MG-63 osteoblast-like cells were used to test cytocompatibility, proliferation, mineralization, and alkaline phosphatase (ALP) activity. The release of 27 cytokines and growth factors was quantified by multiplex immunoassay. Alb-PRF exhibited morphological integrity and an enhanced trophic secretome, and supported proliferation and late mineralization. nCHA incorporation reduced cell proliferation and secretome output, while DOX conferred sustained antibacterial activity and enhanced early ALP expression even with attenuated cytokine release, positively impacting mineralization, when compared to nCHA alone. These preliminary results provide preliminary feasibility evidence that Alb-PRF can be engineered as a multifunctional scaffold combining antimicrobial and regenerative functions, though some trade-offs indicate the need for dose optimization and validation with in vivo models.