Search Results (31)

When placing dental implants, xenografts are most commonly used clinically to compensate for the insufficient bone volume of patients. However, xenografts have limitations including low osteoinductive capacity and prolonged healing time. This study aimed to determine whether non-thermal plasma treatment could enhance the regenerative performance of bovine cancellous bone graft (SANTA-OSS^®) in a rabbit calvarial defect model. Twenty-four adult male New Zealand white rabbits received bilateral 8 mm critical-size calvarial defects. One defect was filled with untreated SANTA-OSS (control) and the contralateral defect with plasma-treated SANTA-OSS using the ACTILINK™ Reborn device. Animals were sacrificed at 2, 4, and 8 weeks (n = 8 per group) for histomorphometric analysis. The plasma-treated group showed significantly higher new bone area (14.12 ± 0.69%, 18.93 ± 0.68%, and 32.72 ± 0.61% at 2, 4, and 8 weeks) than the control at all time points (p < 0.05). In addition, the experimental group exhibited accelerated graft resorption, larger bone marrow area, greater blood vessel area, and more TRAP-positive osteoclasts compared with the control (p < 0.05). Within the limitations of this study, non-thermal plasma treatment significantly enhanced new bone formation and promoted favorable graft remodeling, while also accelerating graft resorption, increasing bone marrow area, and improving vascularization. These findings suggest that simple chairside plasma activation can improve the regenerative performance of xenografts. Full article

Bone tissue is among the most commonly transplanted tissues worldwide. The treatment of critical-sized bone defects remains a significant challenge, as there is currently no universally accepted experimental model or therapeutic standard. Recent advances in fundamental cell biology are driving a paradigm shift in approaches to bone regeneration, highlighting the transformative potential of biofabrication technologies that integrate tissue engineering with personalized regenerative strategies. Three-dimensional (3D) bioprinting technology enables precise control over the architecture and spatial distribution of cellular and biologically active components, facilitating the creation of complex, personalized bone constructs. Central to this process are bioinks and biomaterials that mimic the extracellular matrix (ECM) and provide an optimal microenvironment for cellular function. Despite the substantial body of accumulated data, a comprehensive theoretical framework for functional bone biofabrication has not yet been fully established, emphasizing both the challenges and the innovative potential of the field. This integrative review synthesizes current knowledge on bone biology—from embryogenesis and cell–matrix interactions to molecular and neural regulation—and links it to the opportunities offered by biofabrication. Particular attention is given to bioinks as mediators between cell biology and engineering sciences, as well as to strategies for creating biomimetic ECM, optimizing scaffold design, and guiding future research toward clinically translatable bone regeneration. Full article

Photobiomodulation (PBM) has shown promising potential to enhance bone regeneration; however, its optimal delivery parameters and interactions with osteoconductive scaffolds remain insufficiently defined. This preclinical study is the first to incorporate a pilot dosimetry evaluation to standardize 980-nm PBM delivery and ensure that effective irradiance reached the target surface of critical-size calvarial defects in mice. The primary aim was to evaluate the effectiveness of this novel 980-nm PBM protocol delivered using either flat-top (FT) or standard Gaussian (ST) handpieces in enhancing bone regeneration in critical-size defects (CSDs), both with and without Bio-Oss^® grafting. A total of 120 adult mice were allocated into twelve experimental groups (n = 10 per group): untreated (control), Bio-Oss^® alone, PBM alone, and PBM combined with Bio-Oss^®, using either FT or ST handpieces, and evaluated at 30 and 60 days. Animals received 980 nm irradiation at 0.6 W (nominal power output–set on laser interface) in continuous-wave mode for 60 s, three times per week, for two consecutive weeks. Pilot dosimetry included power meter measurements to determine the therapeutic power reaching the defect surface area and temperature monitoring to ensure safe energy delivery. The dosimetry study demonstrated that, after accounting for the optical properties of mouse shaved skin and the Bio-Oss^® graft covered with Bio-Gide^® membrane, the effective irradiance reaching the base of the defect surface area was 1.131 W/cm² for the FT handpiece and 0.413 W/cm² for the ST handpiece. This dose was sufficient to induce significant regenerative effects. Histological, Masson’s trichrome, and immunohistochemical analyses for Runx2, OCN, GLI1, CD34, and CTSK were performed to characterize early and late osteogenic events. The combination of PBM and Bio-Oss^® significantly accelerated bone regeneration compared with PBM alone, with the FT handpiece producing the most uniform and advanced osteogenesis. PBM enhanced progenitor activation, osteoblast differentiation, angiogenesis, matrix deposition, and late-stage remodeling, demonstrating a synergistic effect with the scaffold, whereas Bio-Oss^® alone or defect alone showed limited early regenerative potential. These findings highlight the effectiveness of this novel standardized PBM dosimetry and uniform beam profile (FT), supporting their use as a foundation for future randomized controlled trials in craniofacial bone repair. Full article

Bone regeneration remains a clinical challenge, particularly in critical-size defects, motivating the investigation of biomaterials and adjuvant therapies that may support tissue repair. This experimental study evaluated bone healing in critical-size calvarial defects created in rats, using different combinations of regenerative strategies, including heterologous fibrin biopolymer gel, bovine cortical bone biological membrane, and photobiomodulation. Standardized 5.0 mm calvarial defects were surgically created in sixty Wistar rats, which were randomly allocated into six experimental groups according to the filling material and the application or absence of photobiomodulation. The treatments included clot alone, fibrin biopolymer gel, biological membrane, photobiomodulation, or their respective combinations. Animals were euthanized at 14 or 42 days, and bone repair was evaluated by histomorphometric analysis. At 14 days, differences in the extent of newly formed bone were observed among the experimental groups, with higher bone formation values detected in groups receiving combined treatments and lower values in groups treated with fewer regenerative components. At 42 days, all groups showed progression of bone repair, with greater bone formation observed in groups in which a biological membrane was used, regardless of photobiomodulation. Overall, the findings indicate that the association of different regenerative approaches was related to variations in bone repair patterns over time, suggesting that photobiomodulation, when applied in combination with biomaterials, may be associated with differences in early bone healing, without implying a direct causal effect. Full article

Musculoskeletal injuries involving volumetric muscle loss remain difficult to treat due to limited regenerative capacity and the lack of physiologically relevant experimental models. This study introduces a computer-controlled ex vivo mouse hindlimb culturing platform that applies dynamic mechanical loading to evaluate muscle regeneration in a critical-size tibialis anterior (TA) defect. The defect was treated with an injectable myoblast-laden nanofibrous scaffold composed of polycaprolactone nanofibers and collagen (PNCOL). The ex vivo mouse hindlimb culturing platform maintained tissue viability and transmitted physiological strain across bone and muscle without disrupting the unity of the bone–muscle structure. PNCOL treatment under mechanical loading enhanced muscle fiber organization, extracellular matrix regeneration, and anti-inflammatory responses (CD206) while upregulating paired box 7 (PAX7), myogenic factor 5 (MYF5), myogenic regulatory factor 4 (MRF4), and transforming growth factor beta1 (TGFβ1) expression. Cytokine profiling revealed an anabolic shift involving wingless/integrated (WNT) and insulin-like growth factor-1 (IGF-1) signaling, indicating a pro-regenerative microenvironment. Overall, the combination of mechanical stimulation and biomaterial-based therapy significantly improved muscle regeneration within a controlled ex vivo model. This multidimensional approach provides a reproducible and ethical platform that advances musculoskeletal regenerative research while reducing animal use. Full article

Background/Objectives: Regenerating critical-sized bone defects is a significant clinical challenge. Autogenous bone grafts are the gold standard but have limitations, including donor site morbidity. As an alternative, this study introduces a novel biocomposite combining an ethyl cyanoacrylate (ECA) polymer with Hancornia speciosa (Hs) latex. The ECA acts as a scaffold and delivery vehicle for the latex, which contains phytochemicals with known angiogenic properties. Methods: We created 5 mm critical-sized calvarial defects in 36 Wistar rats, which were divided into four experimental groups. Bone regeneration was evaluated at 30, 60, and 90 days using micro-computed tomography (micro-CT) for morphometric analysis and hematoxylin and eosin staining for histology. Results: The composite-treated group (Hs+ECA) showed significantly higher bone volume (57.2; IQR: 56.7–61.2) than the control (53.9; IQR: 49.4–56.4) and ECA-only (48.4; IQR: 47.2–59.9) groups at 90 days (p < 0.05). By day 60, the bone volume in the Hs+ECA group was statistically similar (p > 0.05) to that of the autogenous bone group. Histological analysis revealed an organized repair process with neoangiogenesis observed only in the Hs+ECA group, confirming the material’s strong bioactivity. Conclusions: The Hs+ECA composite is a promising biomaterial that acts as an effective delivery system for the bioactive components of the latex. The induced angiogenesis was critical to its regenerative success. This cost-effective material warrants further investigation for clinical applications in regenerative dentistry. Full article

Aim: to evaluate the bone regeneration capacity of two alloplastic biomaterials in a critical-size rat calvarial defect model. Methods: A total of 80 rats were randomized into 8 groups of 10 animals each. An Ø8 mm, critical-size calvarial defect was created, and the following treatments were randomly allocated: sham surgery, deproteinized bovine bone mineral (DBBM) + collagen membrane (CM), poly-(lactic-co-glycolic-acid) (PLGA)-coated pure phase β-tricalcium phosphate (β-TCP), or PLGA-coated 60% hydroxyapatite (HA):40%β-TCP. Animals were allowed to heal for 2 and 6 weeks. Microcomputed tomography (μCT) was used to evaluate mineralized tissue and biomaterial displacement. Histological samples were used to evaluate new bone formation. Results: μCT analysis showed no significant differences among groups for total volume of mineralized tissue or residual biomaterials. DBBM + CM showed significantly increased horizontal biomaterial displacement at 2 weeks but not at 6 weeks. Histological analysis showed that sham surgery had a significantly higher percentage of bone area fraction than the DBBM + CM and PLGA + β-TCP at 2 weeks, but not at 6 weeks. Residual biomaterial area fraction showed no significant differences among experimental groups at any healing time. Conclusions: The alloplastic biomaterials showed suitable construct integrity and retention in the defect. All biomaterials were associated with limited new bone formation comparable to the sham surgery control. Full article

Background: Bone healing is a complex process controlled by various mechanisms. It is known that cigarette smoking (CS) negatively affects bone healing by disrupting many of these mechanisms. In an effort to find ways to eliminate these negative effects caused by CS, studies have been conducted on various vitamins, antioxidants, and medications. Since high doses and repeated injections are required to increase the therapeutic effect of conventional drug applications, controlled drug delivery systems have been developed to avoid such problems. This study aimed to investigate the effects of resveratrol (RES), which has been made into a controlled drug delivery system, on bone healing in rats that were experimentally exposed to cigarette smoke to create a chronic smoking model. Methods: After establishing a chronic CS model by exposing the subjects to cigarette smoke of six cigarettes/day for four weeks, monocortical critical size defects of 3 mm (SD ± 0.02 mm) in diameter were created in the femur using a trephine bur. During the operation, the defects in RES groups were filled locally with a gel-formed solution of RES (50 µM) and Pluronic F-127 (14 µL). CS exposure was continued during the bone healing period after surgery. All groups were sacrificed one month after the operation, and femur samples were taken. Results: The obtained samples were examined by histomorphometric and immunohistochemical techniques; osteoblast count, new bone area, macroscopic filling score, vascularization, and proliferation were evaluated. Conclusion: The results of this study indicate that CS negatively affects bone healing and that local application of RES reduces this effect. Full article

Background: Guided bone regeneration (GBR) has become a necessary practice in implantology. Absorbable membranes have shown advantages over non-absorbable membranes, such as blood support of bone tissue. This study aimed to evaluate five collagen membranes in rat calvaria critical-size defects through a histomorphometric analysis of the inflammatory profile during the initial phase of bone repair. Materials and methods: A total of 72 Albinus Wistar rats were used for the study, divided into six groups, with 12 animals per group, and two experimental periods, 7 and 15 days. The groups were as follows: the CG (clot), BG (Bio-Gide^®), JS (Jason^®), CS (Collprotect^®), GD (GemDerm^®), and GDF (GemDerm Flex^®). Results: Data showed that the BG group demonstrated an inflammatory profile with an ideal number of inflammatory cells and blood vessels, indicating a statistically significant difference between the JS and CS groups and the BG group in terms of the number of inflammatory cells and a statistically significant difference between the JS and CS groups and the GD group in terms of angiogenesis (p < 0.05). Conclusions: We conclude that different origins and ways of obtaining them, as well as the thickness of the membrane, can interfere with the biological response of the material. Full article

Background: A critical-sized bone defect (CsBD) is considered one that will not heal spontaneously and requires reconstruction. This study aims to compare the results of using different bone reconstructive techniques and to study the potential of platelet-rich fibrin (PRF) to enhance the healing properties of a bone substitute (BS). Methods: In this experimental study on rats, the treatment of critical-sized bone defects was carried out by analysing four groups: a control group in which the bone defect was left empty; a group treated with Bio-Gen^®; another group in which the defect was treated with PRF in combination with Bio-Gen^®; and the last that was treated with autologous bone graft (ABG). The defects were evaluated by microcomputed tomography (µCT) and then histomorphometrically. Results: From both the histological and imagistic point of view, the best results were registered in the ABG group, followed by the group treated with Bio-Gen^® with PRF, Bio-Gen^® group, and control group, with statistically significant differences. Conclusions: A 5 mm defect in the rat radius can be considered critical. ABG showed the best results in treating the bone defect. PRF significantly enhanced the efficacy of Bio-Gen^®. Full article

Bone defects may be a result of different pathologies and represent a challenge in different fields of dentistry. Techniques for the correction of bone defects involving the use of several types of grafts have been proposed. This study evaluated bone repair in rat tibiae after surgically created critical-size defects were filled with β-tricalcium phosphate (RTR^®, Septodont, FR). Critical-size bone defects were created in the tibiae of 32 male Wistar rats, which were divided into four groups (n = 8): Control 30 days, Control 90 days, RTR^® 30 days, and RTR^® 90 days. After the experimental period, the animals were euthanized and specimens were collected, embedded in paraffin, serially cut, and stained with hematoxylin and eosin to evaluate the inflammatory and repair response. Two parameters were analyzed: neoformed bone tissue areas (NBA) and neoformed cortical areas (NCA). Statistical analysis was performed by ANOVA and Tukey’s test (p < 0.05). The RTR^® group demonstrated superior bone healing compared with the control group in both analyzed parameters (NBA and NCA), with repair of the cortical bone and bone-tissue formation in the central region of the defect, which showed partial repair in the defect area (p < 0.05). RTR^® enhanced bone neoformation in the adopted experimental model and may be a useful biomaterial to boost healing in cases of critical-size bone defects. Full article

A biomaterial is proposed for closing extensive bone defects in the maxillofacial region. The composition of the biomaterial includes high-molecular chitosan, chondroitin sulfate, hyaluronate, heparin, alginate, and inorganic nanostructured hydroxyapatite. The purpose of this study is to demonstrate morphological and histological early signs of reconstruction of a bone cavity of critical size. The studies were carried out on 84 white female rats weighing 200–250 g. The study group consisted of 84 animals in total, 40 in the experimental group and 44 in the control group. In all animals, three-walled bone defects measuring 0.5 × 0.4 × 0.5 cm³ were applied subperiosteally in the region of the angle of the lower jaw and filled in the experimental group using lyophilized gel mass of chitosan–alginate–hydroxyapatite (CH–SA–HA). In control animals, the bone cavities were filled with their own blood clots after bone trepanation and bleeding. The periods for monitoring bone regeneration were 3, 5, and 7 days and 2, 3, 4, 6, 8, and 10 weeks. The control of bone regeneration was carried out using multiple morphological and histological analyses. Results showed that the following process is an obligatory process and is accompanied by the binding and release of angiogenic implantation: the chitosan construct actively replaced early-stage defects with the formation of full-fledged new bone tissue compared to the control group. By the 7th day, morphological analysis showed that the formation of spongy bone tissue could be seen. After 2 weeks, there was a pronounced increase in bone volume (p < 0.01), and at 6 weeks after surgical intervention, the closure of the defect was 70–80%; after 8 weeks, it was 100% without violation of bone morphology with a high degree of mineralization. Thus, the use of modified chitosan after filling eliminates bone defects of critical size in the maxillofacial region, revealing early signs of bone regeneration, and serves as a promising material in reconstructive dentistry. Full article

This study aimed to assess the bone regeneration of critical-size defects in rabbit calvaria filled with freshly crushed extracted teeth, comparing them with BTCP biomaterial and empty sites. Materials and methods: Twenty-one female New Zealand rabbits were used in this study. Two critical-size defects 6 mm in size were created in the skull bone, each with a 3 mm separation between them. Three experimental groups were evaluated: Group A (human sterilized crushed teeth granules alone), Group B (Bioner Bone, Bioner Sitemas Implantológicos), and Group C (unfilled defects). The animals were sacrificed at 4 and 8 weeks. Evaluation of the samples involved histological and histomorphometric analyses with radiographic evaluation. The histological evaluation showed a higher volume reduction in Group A compared with Group B (p < 0.05) and Control. Group A showed the highest values for cortical closure and bone formation around the particles, followed by Group B and Group C (p < 0.05). Within the limitations of this animal study, we can conclude that the use of human tooth particles leads to increased bone formation and reduced connective tissue in critical-size defects in rabbit calvaria when compared to BTCP biomaterial. The calvarial model is a robust base for the evaluation of different biomaterials. Full article

The objective of this study was to evaluate the efficacy of photobiomodulation in the bone regeneration of critical-sized defects (CSD) filled with inorganic bovine bone associated or not with collagen membranes. The study has been conducted on 40 critical defects in the calvaria of male rats, divided into four experimental groups (n = 10): (1) DBBM (deproteinized bovine bone mineral); (2) GBR (DBBM+collagen membrane); (3) DBBM+P (DBBM+photobiomodulation); and (4) GBR+P (GBR+photobiomodulation). At 30 days postoperative, the animals were euthanized, and after the tissue had been processed, histological, histometric, and statistical analyses were performed. The analyses have taken into account newly formed bone area (NBA), linear bone extension (LBE), and residual particle area (RPA) as variables. The Kruskal-Wallis test has been performed, followed by the Dwass-Steel-Critchlow-Fligner test for comparison between groups (p < 0.05). When the DBBM+P group was compared to the DBBM group, it was possible to observe significant statistical differences in all the variables analyzed (p < 0.05). The application of photobiomodulation in guided bone regeneration (GBR+P) has shown a decrease in the median value for the RPA variable (26.8) when compared to the GBR group (32.4), with a significant statistical difference; however, for NBA and LBE, the therapy has not provided significant results. Full article

Electrospinning has recently been recognized as a potential method for use in biomedical applications such as nanofiber-based drug delivery or tissue engineering scaffolds. The present study aimed to demonstrate the electrospinning preparation and suitability of β-tricalcium phosphate-modified aerogel containing polyvinyl alcohol/chitosan fibrous meshes (BTCP-AE-FMs) for bone regeneration under in vitro and in vivo conditions. The mesh physicochemical properties included a 147 ± 50 nm fibrous structure, in aqueous media the contact angles were 64.1 ± 1.7°, and it released Ca, P, and Si. The viability of dental pulp stem cells on the BTCP-AE-FM was proven by an alamarBlue assay and with a scanning electron microscope. Critical-size calvarial defects in rats were performed as in vivo experiments to investigate the influence of meshes on bone regeneration. PET imaging using ¹⁸F-sodium fluoride standardized uptake values (SUVs) detected 7.40 ± 1.03 using polyvinyl alcohol/chitosan fibrous meshes (FMs) while 10.72 ± 1.11 with BTCP-AE-FMs after 6 months. New bone formations were confirmed by histological analysis. Despite a slight change in the morphology of the mesh because of cross-linking, the BTCP-AE-FM basically retained its fibrous, porous structure and hydrophilic and biocompatible character. Our experiments proved that hybrid nanospun scaffold composite mesh could be a new experimental bone substitute bioactive material in future medical practice. Full article