Search Results (68)

This systematic review aimed to evaluate the effectiveness of teriparatide (TP) in guided bone regeneration (GBR). An electronic search without language or date restrictions was performed in PubMed, Web of Science, Scopus, Scielo, and gray literature for articles published until June 2025. Inclusion criteria considered studies evaluating the effect of TP on bone regeneration, analyzed using SYRCLE’s Risk of Bias tool. Twenty-four preclinical studies were included, covering diverse craniofacial models (mandibular, calvarial, extraction sockets, sinus augmentation, distraction osteogenesis, segmental defects) and employing systemic or local TP administration. Teriparatide consistently enhanced osteogenesis, graft integration, angiogenesis, and mineralization, with potentiated effects when combined with various biomaterials, including polyethylene glycol (PEG), hydroxyapatite/tricalcium phosphate (HA/TCP), biphasic calcium phosphate (BCP), octacalcium phosphate collagen (OCP/Col), enamel matrix derivatives (EMDs), autografts, allografts, xenografts (Bio-Oss), strontium ranelate, and bioactive glass. Critically, most studies presented a moderate-to-high risk of bias, with insufficient randomization, allocation concealment, and blinding, which limited the internal validity of the findings. TP shows promising osteoanabolic potential in guided bone regeneration, enhancing bone formation, angiogenesis, and scaffold integration across preclinical models. Nonetheless, its translation to clinical practice requires well-designed human randomized controlled trials to define optimal dosing strategies, long-term safety, and its role in oral and craniomaxillofacial surgical applications. Full article

Magnesium whitlockite (Mg-WH) has emerged as a promising biomaterial for bone regeneration due to its compositional similarity to natural bone minerals. This study aimed to systematically modify a dissolution–precipitation synthesis method to produce Mg-WH granules with tailored morphologies and controlled phase compositions for possible use in bone regeneration applications. Three distinct precursor granules were prepared by mixing varying amounts of ammonium dihydrogen phosphate and magnesium hydrogen phosphate with calcium sulfate. The precursors were then transformed into biphasic and single-phase Mg-WH granules by means of immersion in magnesium- and phosphate-containing solutions under controlled conditions. The X-ray diffraction results demonstrated that biphasic materials containing Mg-WH and either calcium-deficient hydroxyapatite (CDHA) or dicalcium phosphate anhydrous (DCPA) formed after 24 h of synthesis, depending on the synthesis conditions. Prolonging the reaction time to 48 h resulted in complete transformation into single-phase Mg-WH granules. Fourier-transform infrared spectroscopy confirmed the presence of functional groups characteristic of Mg-WH, CDHA, and DCPA in the intermediate products. The spectra also indicated the absence of precursor phases and the progressive elimination of secondary phases as the reaction time increased. Scanning electron microscopy analyses revealed notable morphological transformations from the raw granules to the product granules, with the latter exhibiting interlocked spherical and rod-like particles composed of fine Mg-WH rhombohedral crystals. N₂ adsorption–desorption analyses exposed significant differences in the surface properties of the synthesized granules. By varying precursor, reaction solution compositions, and reaction times, the study elucidated the phase evolution mechanisms and demonstrated their impact on the structural, morphological, and surface properties of Mg-WH granules. Full article

The expansion of fisheries and aquaculture in recent decades has led to a substantial increase in fish by-products. This study investigates the extraction and characterization of calcium phosphates from the by-products of representative species in these industries, aiming to identify potential sources for biotechnological and pharmaceutical applications. Clean bones obtained by enzyme hydrolysis from the heads, central skeletons, and/or tails of Atlantic horse mackerel, blue whiting, hake, mackerel, and farmed turbot were subjected to calcination to obtain calcium phosphates. The clean bone content in terms of nitrogen, lipids, organic matter, total protein, and amino acids was evaluated together with the chemical bonds, structures, and elemental composition of calcium phosphates. Results indicated a significantly higher yield of wet bone recovery (23%, p < 0.05) for the central skeleton of Atlantic horse mackerel and the highest mineral fraction for the heads of Atlantic horse mackerel (73.2%), followed by that of blue whiting (72.6%). Hake and turbot presented the lowest mineral fractions and, therefore, the highest protein content (27–31%, p < 0.05), with significant levels of collagen-related amino acids (p < 0.05). X-ray diffraction (XRD) and Fourier-transform Raman spectroscopy (FT-Raman) confirmed the biphasic calcium phosphate composition for most samples based on hydroxyapatite with contributions of whitlockite/β-tricalcium phosphate. The highest contribution to the non-apatite phase was made by the central skeletons of both mackerel and Atlantic horse mackerel. 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

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

Bone regeneration is a highly dynamic and complex process that involves hematopoietic stem cells and mesenchymal cells, collagen fibers, non-collagenous proteins and biomolecules from extracellular matrices, and different cytokines and immune cells, as well as growth factors and hormones. Some phytochemicals due to antioxidant and anti-inflammatory effects can modulate the bone signaling pathways and improve bone healing and thus can be a good candidate for osteoregeneration. The aim of this study was to analyze the impact of Juglans regia L. extract compared to ellagic acid on bone neoformation in rats. The animals with a 5 mm calvaria defect were divided into four groups (n = 10): group 1 was treated with ellagic acid 1% (EA), group 2 was treated with Juglans regia L. extract 10% (JR), group 3 was treated with a biphasic mix of hydroxyapatite and tricalcium phosphate (Ceraform), and group 4 was treated with vehicle inert gel with carboxymethylcellulose (CMC). After 3 weeks of treatment, blood samples were collected for oxidative stress and inflammation assessment. Additionally, the receptor activator of nuclear factor kappa-Β ligand (RANKL) and hydroxyproline levels were quantified in blood. The skull samples were analyzed by scanning electron microscopy in order to detect the modifications in the four groups. The results suggested that JR extract had relevant anti-oxidant effect and bone protective activity and generated the accumulation of Ca and P, demonstrating the potential therapeutic abilities in bone regeneration. Full article

The global tuna canning industry generates substantial volumes of by-products, comprising 50% to 70% of the total processed material. Traditionally, these by-products have been utilized in low-value products such as fish oils and fishmeal. However, there is significant potential to extract high-value compounds from these by-products, such as calcium phosphates (CaP), which can have pharmaceutical, agricultural and biotechnological applications. This work explores the potential of tuna canning by-products, particularly mineral-rich fractions (central skeleton, head and fish bones) as sources of calcium phosphates (CaP), offering a sustainable alternative to conventional synthetic derivatives within a circular bioeconomy framework. By-products from two of the most exploited species (yellowfin and skipjack) were subjected to enzymatic hydrolysis and chemical extraction, followed by controlled calcination to obtain CaP. The content of organic matter, nitrogen, total proteins, lipids and amino acids in the cleaned bones, as well as the main chemical bonds, structure and elemental composition (FT-Raman, XRD, XRF) were evaluated. Results indicated that the highest recovery yield of wet bones was achieved using the chemical method, particularly from the dorsal and caudal fins of yellowfin tuna. The proximal composition, with ash content ranging from 52% to 66% and protein content varying between 30% and 53%, highlights the potential of tuna skeleton substrates for plant growth formulations. Furthermore, variations in crystalline structures of the substrates revealed significant differences depending on the by-product source and species. XRD and Raman results confirmed a monophase calcium phosphate composition in most samples from both species, primarily based on hydroxyapatite (central skeleton, caudal and dorsal fin) or whitlockite/β-tricalcium phosphate (viscera), whereas the heads exhibited a biphasic composition. Comparing the species, yellowfin tuna (YF) exhibited a hydroxyapatite structure in the branchial arch and scales, while skipjack (SKJ) had a biphasic composition in these same regions. 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

The reunion and restoration of large segmental bone defects pose significant clinical challenges. Conventional strategies primarily involve the combination of bone scaffolds with seeded cells and/or growth factors to regulate osteogenesis and angiogenesis. However, these therapies face inherent issues related to immunogenicity, tumorigenesis, bioactivity, and off-the-shelf transplantation. The biogenic micro-environment created by implanted bone grafts plays a crucial role in initiating the bone regeneration cascade. To address this, a highly porous bi-phasic ceramic synthetic bone graft, composed of hydroxyapatite (HA) and alumina (Al), was developed. This graft was employed to repair critical segmental defects, involving the creation of a 2 cm segmental defect in a canine tibia. The assessment of bone regeneration within the synthetic bone graft post-healing was conducted using scintigraphy, micro-CT, histology, and dynamic histomorphometry. The technique yielded pore sizes in the range of 230–430 μm as primary pores, 40–70 μm as secondary inner microchannels, and 200–400 nm as tertiary submicron surface holes. These three components are designed to mimic trabecular bone networks and to provide body fluid adsorption, diffusion, a nutritional supply, communication around the cells, and cell anchorage. The overall porosity was measured at 82.61 ± 1.28%. Both micro-CT imaging and histological analysis provided substantial evidence of robust bone formation and the successful reunion of the critical defect. Furthermore, an histology revealed the presence of vascularization within the newly formed bone area, clearly demonstrating trabecular and cortical bone formation at the 8-week mark post-implantation. Full article

Pollen grains, with their resilient sporopollenin exine and defined morphologies, have been explored as bio-templates for the synthesis of calcium phosphate minerals, particularly hydroxyapatite (HAp) and β-tricalcium phosphate (TCP). Various pollen morphologies from different plant species (black alder, dandelion, lamb’s quarters, ragweed, and stargazer lily) were evaluated. Pollen grains underwent acid washing to remove allergenic material and facilitate subsequent calcification. Ragweed and lamb’s quarter pollen grains were chosen as templates for calcium phosphate salts deposition due to their distinct morphologies. The calcification process yielded well-defined spherical hollow particles. The washing step, intended to reduce the protein content, did not significantly affect the final product; thus, justifying the removal of this low-yield step from the synthesis process. Characterisation techniques, including X-ray diffraction, scanning electron microscopy, Fourier-transform infrared spectroscopy, and thermal gravimetric analysis, confirmed the successful calcification of pollen-derived materials, revealing that calcified grains were principally composed of calcium deficient HAp. After calcination, biphasic calcium phosphate composed of HAp and TPC was obtained. This study demonstrated the feasibility of using pollen grains as green and sustainable bio-templates for synthesizing biomaterials with controlled morphology, showcasing their potential in biomedical applications such as drug delivery and bone regeneration. Full article

The incidence of microbial infections in orthopedic prosthetic surgeries is a perennial problem that increases morbidity and mortality, representing one of the major complications of such medical interventions. The emergence of novel technologies, especially 3D printing, represents a promising avenue of development for reducing the risk of such eventualities. There are already a host of biomaterials, suitable for 3D printing, that are being tested for antimicrobial properties when they are coated with bioactive compounds, such as antibiotics, or combined with hydrogels with antimicrobial and antioxidant properties, such as chitosan and metal nanoparticles, among others. The materials discussed in the context of this paper comprise beta-tricalcium phosphate (β-TCP), biphasic calcium phosphate (BCP), hydroxyapatite, lithium disilicate glass, polyetheretherketone (PEEK), poly(propylene fumarate) (PPF), poly(trimethylene carbonate) (PTMC), and zirconia. While the recent research results are promising, further development is required to address the increasing antibiotic resistance exhibited by several common pathogens, the potential for fungal infections, and the potential toxicity of some metal nanoparticles. Other solutions, like the incorporation of phytochemicals, should also be explored. Incorporating artificial intelligence (AI) in the development of certain orthopedic implants and the potential use of AI against bacterial infections might represent viable solutions to these problems. Finally, there are some legal considerations associated with the use of biomaterials and the widespread use of 3D printing, which must be taken into account. Full article

Many studies have been exploring the use of bone graft materials (BGMs) and mesenchymal stem cells in bone defect reconstruction. However, the regeneration potential of Algipore (highly purified hydroxyapatite) and Biphasic (hydroxyapatite/beta-tricalcium phosphate) BGMs combined with bone marrow–derived mesenchymal stem cells (BMSCs) remains unclear. Therefore, we evaluated their osseointegration capacities in reconstructing peri-implant bone defects. The cellular characteristics of BMSCs and the material properties of Algipore and Biphasic were assessed in vitro. Four experimental groups—Algipore, Biphasic, Algipore+BMSCs, and Biphasic+BMSCs—were designed in a rabbit tibia peri-implant defect model. Implant stability parameters were measured. After 4 and 8 weeks of healing, all samples were evaluated using micro-CT, histological, and histomorphometric analysis. In the energy-dispersive X-ray spectroscopy experiment, the Ca/P ratio was higher for Algipore (1.67) than for Biphasic (1.44). The ISQ values continuously increased, and the PTV values gradually decreased for all groups during the healing period. Both Algipore and Biphasic BGM promoted new bone regeneration. Higher implant stability and bone volume density were observed when Algipore and Biphasic BGMs were combined with BMSCs. Biphasic BGM exhibited a faster degradation rate than Algipore BGM. Notably, after eight weeks of healing, Algipore with BSMCs showed more bone–implant contact than Biphasic alone (p < 0.05). Both Algipore and Biphasic are efficient in reconstructing peri-implant bone defects. In addition, Algipore BGM incorporation with BSMCs displayed the best performance in enhancing implant stability and osseointegration potential. Full article

This study focuses on developing hydroxyapatite synthesized from a CaCO₃-rich byproduct of sugar beet processing called Carbocal^® using a hydrothermal reactor. The purpose of this biomaterial is to enhance the osteoinductivity of implantable surfaces and serve as a bone filler, providing a sustainable and economically more affordable alternative. This research involved compositional analysis and micro- and macrostructural physicochemical characterization, complemented with bioactivity and live/dead assays. The biphasic nature of the Carbocal^®-derived sample was significant within the context of the bioactivity concept previously proposed in the literature. The bioactivity of the biomaterial was demonstrated through a viability test, where the cell growth was nearly equivalent to that of the positive control. For comparison purposes, the same tests were conducted with two additional samples: hydroxyapatite obtained from CaCO₃ and commercial hydroxyapatite. The resulting product of this process is biocompatible and possesses properties similar to natural hydroxyapatite. Consequently, this biomaterial shows potential as a scaffold in tissue engineering and as an adhesive filler to promote bone regeneration within the context of the circular bioeconomy in the geographical area proposed. Full article

We extracted magnesium-rich calcium phosphate bioceramics from tilapia bone using a gradient thermal treatment approach and investigated their chemical and physicochemical properties. X-ray diffraction showed that tilapia fish bone-derived hydroxyapatite (FHA) was generated through the first stage of thermal processing at 600–800 °C. Using FHA as a precursor, fish bone biphasic calcium phosphate (FBCP) was produced after the second stage of thermal processing at 900–1200 °C. The beta-tricalcium phosphate content in the FBCP increased with an increasing calcination temperature. The fact that the lattice spacing of the FHA and FBCP was smaller than that of commercial hydroxyapatite (CHA) suggests that Mg-substituted calcium phosphate was produced via the gradient thermal treatment. Both the FHA and FBCP contained considerable quantities of magnesium, with the FHA having a higher concentration. In addition, the FHA and FBCP, particularly the FBCP, degraded faster than the CHA. After one day of degradation, both the FHA and FBCP released Mg²⁺, with cumulative amounts of 4.38 mg/L and 0.58 mg/L, respectively. Furthermore, the FHA and FBCP demonstrated superior bone-like apatite formation; they are non-toxic and exhibit better osteoconductive activity than the CHA. In light of our findings, bioceramics originating from tilapia bone appear to be promising in biomedical applications such as fabricating tissue engineering scaffolds. Full article

Osteoarthritis is a prevalent musculoskeletal disorder in the elderly, which leads to high rates of morbidity. Mesenchymal stem cells (MSCs) are a promising approach to promote tissue regeneration in the absence of effective long-term treatments. Small molecules are relatively inexpensive and can selectively alter stem cell behavior during their differentiation, making them an attractive option for clinical applications. In this study, we developed an extracellular matrix (ECM)-based biphasic scaffold (BPS) loaded with two small-molecule drugs, kartogenin (KGN) and metformin (MET). This cell-free biomimetic biphasic scaffold consists of a bone (gelatin/hydroxyapatite scaffold embedded with metformin [GHSM]) and cartilage (nano-gelatin fiber embedded with kartogenin [NGFK]) layer designed to stimulate osteochondral regeneration. Extracellular matrix (ECM)-based biomimetic scaffolds can promote native cell recruitment, infiltration, and differentiation even in the absence of additional growth factors. The biphasic scaffold (BPS) showed excellent biocompatibility in vitro, with mesenchymal stem cells (MSCs) adhering, proliferating, and differentiated on the biomimetic biphasic scaffolds (GHSM and NGFK layers). The biphasic scaffolds upregulated both osteogenic and chondrogenic gene expression, sulfated glycosaminoglycan (sGAG), osteo- and chondrogenic biomarker, and relative mRNA gene expression. In an in vivo rat model, histo-morphological staining showed effective regeneration of osteochondral defects. This novel BPS has the potential to enhance both subchondral bone repair and cartilage regeneration, demonstrating excellent effects on cell homing and the recruitment of endogenous stem cells. Full article