Platelet Rich Fibrin Matrix (PRFM) and Peripheral Blood Mesenchymal Stem Cells (PBMSCs) in the management of intraosseous defects - A randomized clinical trial.

OBJECTIVE: A combination of peripheral blood mesenchymal stem cells (PBMSCs) and platelet rich fibrin matrix (PRFM) could be a probable periodontal regenerative material with the synergy of the added benefits of each material. This randomized controlled clinical trial aimed to evaluate the regenerative capacity of supercell (PRFM and PBMSCs) compared with that of PRFM alone in human periodontal mandibular intraosseous defects (IOD). METHODOLOGY: This study included 17 patients of both sexes (12 men, 5 women) aged 30-55 years (mean age = 37.7±4.4 years) who fulfilled the inclusion criteria (radiographic and clinical evaluation for bilateral IOD with probing pocket depth (PPD ≥ 6 mm). A split-mouth design was used in each patient. A total of 34 sites in the mandibular arch randomly received PRFM alone + open flap debridement (OFD) [Control sites] or supercell (PRFM+PBMSCs) + OFD [Test sites]. The clinical parameters plaque index (PI), gingival index (GI), PPD, clinical attachment level (CAL), and in the radiographic parameters; defect depth (DD) and defect fill percentage (DFP) were recorded at baseline, 3 and 6 months postoperatively. Early wound healing index (EHI) was used at 1 week to assess wound healing ability. RESULTS: At 6 months, radiographic parameters revealed significant reduction in DD (P<0.001) and significant DFP values in the test group compared with the control group. The supercell showed significant improvement in PPD and CAL at the end of 6 months (P<0.001). EHI scores at 1 week showed no statistically significant difference between the test and control groups. CONCLUSION: Supercell can be considered a regenerative material in the treatment of periodontal IODs.

Biological evaluation of critical bone defect regeneration using hydroxyapatite/ alginate composite granules.

PURPOSE: to evaluate biocompatibility and osteogenic potential of hydroxyapatite/alginate composite after its implantation on rat calvarian critical bone defect. METHODS: thirty adults male Wistar rats were randomly distributed into two groups: GHA - critical bone defect filled with hydroxyapatite/alginate composite granules (HA/Alg) and CG - critical bone defect without biomaterial; evaluated at biological points of 15, 45 and 120 days. RESULTS: the histomorphometrically analyses for GHA showed osteoid matrix deposition (OM) among the granules and towards the center of the defect in centripetal direction throughout the study, with evident new bone formation at 120 days, resulting in filling 4/5 of the initial bone defect. For CG, this finding was restricted to the edges of the bone margins and formation of connective tissue on the residual area was found in all biological points. Inflammatory response on GHA was chronic granulomatous type, discrete and regressive for all biological points. Throughout the study, the CG presented mononuclear inflammatory infiltrate diffuse and regressive. Histomorphometry analyses showed that OM percentage was evident for GHA group when compared to CG group in all analyzed periods (p > 0.05). CONCLUSIONS: the biomaterial evaluated at this study showed to be biocompatible, bioactive, osteoconductive and biodegradable synchronously with bone formation.

Contribution of initial lymphatics to oral wound healing after tooth extraction.

Lymphatics are involved in the resolution of inflammation and wound healing, but their role in the oral wound healing process after tooth extraction has never been investigated. We therefore sought to evaluate the healing process following the extraction of maxillary molars in two transgenic mouse models: K14-VEGFR3-Ig mice, which lack initial mucosal lymphatic vessels, and K14-VEGFC mice, which have hyperplastic mucosal lymphatics. Maxillary molars were extracted from both transgenic mouse types and their corresponding wild-type (WT) controls. Mucosal and alveolar bone healing were evaluated. A delayed epithelialization and bone regeneration were observed in K14-VEGFR3-Ig mice compared with their WT littermates. The hampered wound closure was accompanied by decreased levels of epidermal growth factor (EGF) and persistent inflammation, characterized by infiltrates of immune cells and elevated levels of pro-inflammatory markers in the wounds. Hyperplastic mucosal lymphatics did not enhance the healing process after tooth extraction in K14-VEGFC mice. The findings indicate that initial mucosal lymphatics play a major role in the initial phase of the oral wound healing process.

Requirement of Pdgfrα+ cells for calvarial bone repair.

Platelet-derived growth factor receptor α (PDGFRα) is often considered as a general marker of mesenchymal cells and fibroblasts, but also shows expression in a portion of osteoprogenitor cells. Within the skeleton, Pdgfrα+ mesenchymal cells have been identified in bone marrow and periosteum of long bones, where they play a crucial role in participating in fracture repair. A similar examination of Pdgfrα+ cells in calvarial bone healing has not been examined. Here, we utilize Pdgfrα-CreERTM;mT/mG reporter animals to examine the contribution of Pdgfrα+ mesenchymal cells to calvarial bone repair through histology and single-cell RNA sequencing (scRNA-Seq). Results showed that Pdgfrα+ mesenchymal cells are present in several cell clusters by scRNA-Seq, and by histology a dramatic increase in Pdgfrα+ cells populated the defect site at early timepoints to give rise to healed bone tissue overtime. Notably, diphtheria toxin-mediated ablation of Pdgfrα reporter+ cells resulted in significantly impaired calvarial bone healing. Our findings suggest that Pdgfrα-expressing cells within the calvarial niche play a critical role in the process of calvarial bone repair.

Angiogenesis is uncoupled from osteogenesis during calvarial bone regeneration.

Bone regeneration requires a well-orchestrated cellular and molecular response including robust vascularization and recruitment of mesenchymal and osteogenic cells. In femoral fractures, angiogenesis and osteogenesis are closely coupled during the complex healing process. Here, we show with advanced longitudinal intravital multiphoton microscopy that early vascular sprouting is not directly coupled to osteoprogenitor invasion during calvarial bone regeneration. Early osteoprogenitors emerging from the periosteum give rise to bone-forming osteoblasts at the injured calvarial bone edge. Microvessels growing inside the lesions are not associated with osteoprogenitors. Subsequently, osteogenic cells collectively invade the vascularized and perfused lesion as a multicellular layer, thereby advancing regenerative ossification. Vascular sprouting and remodeling result in dynamic blood flow alterations to accommodate the growing bone. Single cell profiling of injured calvarial bones demonstrates mesenchymal stromal cell heterogeneity comparable to femoral fractures with increase in cell types promoting bone regeneration. Expression of angiogenesis and hypoxia-related genes are slightly elevated reflecting ossification of a vascularized lesion site. Endothelial Notch and VEGF signaling alter vascular growth in calvarial bone repair without affecting the ossification progress. Our findings may have clinical implications for bone regeneration and bioengineering approaches.

M2 macrophage-derived exosomes for bone regeneration: A systematic review.

OBJECTIVE: This systematic review aims to evaluate existing evidence to investigate the therapeutic efficacy of M2 macrophage-derived exosomes in bone regeneration. DESIGN: A comprehensive search between 2020 and 2024 across PubMed, Web of Science, and Scopus was conducted using a defined search strategy to identify relevant studies regarding the following question: "What is the impact of M2 macrophage-derived exosomes on bone regeneration?". Controlled in vitro and in vivo studies were included in this study. The SYRCLE tool was used to evaluate the risk of bias in the included animal studies. RESULTS: This review included 20 studies published. Seven studies were selected for only in vitro analysis, whereas 13 studies underwent both in vitro and in vivo analyses. The in vivo studies employed animal models, including 163 C57BL6 mice and 73 Sprague-Dawley rats. Exosomes derived from M2 macrophages were discovered to be efficacious in promoting bone regeneration and vascularization in animal models of bone defects. These effects were primarily confirmed through morphological and histological assessments. This remarkable outcome is attributed to the regulation of multiple signaling pathways, as evidenced by the findings of 11 studies investigating the involvement of miRNAs in this intricate process. In addition, in vitro studies observed positive effects on cell proliferation, migration, osteogenesis, and angiogenesis. Heterogeneity in study methods hinders direct comparison of results across studies. CONCLUSION: M2 macrophage-derived exosomes demonstrate remarkable potential for promoting bone regeneration. Further research optimizing their application and elucidating the underlying mechanisms can pave the way for clinical translation.

The Masquelet induced membrane technique with PRP-FG-nHA/PA66 scaffold can heal a rat large femoral bone defect.

BACKGROUND: Masquelet membrane induction technology is one of the treatment strategies for large bone defect (LBD). However, the angiogenesis ability of induced membrane decreases with time and autologous bone grafting is associated with donor site morbidity. This study investigates if the PRP-FG-nHA/PA66 scaffold can be used as a spacer instead of PMMA to improve the angiogenesis ability of induced membrane and reduce the amount of autologous bone graft. METHODS: Platelet rich plasma (PRP) was prepared and PRP-FG-nHA/PA66 scaffold was synthesized and observed. The sustained release of VEGFA and porosity of the scaffold were analyzed. We established a femur LBD model in male SD rats. 55 rats were randomly divided into four groups depending on the spacer filled in the defect area. "Defect only" group (n = 10), "PMMA" group (n = 15), "PRP-nHA/PA66" group (n = 15) and "PRP-FG-nHA/PA66" group (n = 15 ). At 6 weeks, the spacers were removed and the defects were grafted. The induced membrane and bone were collected and stained. The bone formation was detected by micro-CT and the callus union was scored on a three point system. RESULTS: The PRP-FG-nHA/PA66 scaffold was porosity and could maintain a high concentration of VEGFA after 30 days of preparation. The induced membrane in PRP-FG-nHA/PA66 group was thinner than PMMA, but the vessel density was higher.The weight of autogenous bone grafted in PRP-FG-nHA/PA66 group was significantly smaller than that of PMMA group. In PRP-FG-nHA/PA66 group, the bone defect was morphologically repaired. CONCLUSION: The study showed that PRP-FG-nHA/PA66 scaffold can significantly reduce the amount of autologous bone graft, and can achieve similar bone defect repair effect as PMMA. Our findings provide some reference and theoretical support for the treatment of large segmental bone defects in humans.

Ridge Preservation Combined With Open Barrier Membrane Technique in Case of Postextractive Oroantral Communication: A Case Series Retrospective Study.

After dental extraction, a physiological phenomenon of reabsorption of the dentoalveolar process is triggered, especially if periradicular lesions are present, which can sometimes be associated with oroantral communication in the upper posterior maxilla. To investigate a minimally invasive approach, 19 patients undergoing tooth extraction in the posterosuperior maxilla were recruited. All cases presented an oroantral communication with a diameter of 2-5 mm after tooth extraction and the alveolar process and, in some cases, with a partial defect of 1 or more bony walls. In these cases, a single surgical procedure was used to preserve the alveolar ridge using an open barrier technique with an exposed dense polytetrafluoroethylene membrane. The bottom of the extraction socket was filled with a collagen fleece. The residual bone process was reconstructed using a biomaterial based on carbonate-apatite derived from porcine cancellous bone. After 6 months, all patients were recalled and subjected to radiographic control associated with an implant-prosthetic rehabilitation plan. Data relating to the sinus health status and the average height and thickness of the regenerated bone were collected. Radiographic evaluation verified the integrity of the maxillary sinus floor with new bone formation, detecting a vertical bone dimension between 3.1 mm and 7.4 mm (average 5.13 ± 1.15 mm) and a horizontal thickness between 4.2 mm and 9.6 mm (average 6.86 ± 1.55 mm). The goal of this study was to highlight the advantage of managing an oroantral communication and, simultaneously, obtain the preservation and regeneration of the alveolar bone crest. The open barrier technique appears to be effective for the minimally invasive management of oroantral communication up to 5 mm in diameter in postextraction sites, with a good regeneration of hard and soft tissue.

Stem Cells and Acellular Preparations in Bone Regeneration/Fracture Healing: Current Therapies and Future Directions.

Bone/fracture healing is a complex process with different steps and four basic tissue layers being affected: cortical bone, periosteum, fascial tissue surrounding the fracture, and bone marrow. Stem cells and their derivatives, including embryonic stem cells, induced pluripotent stem cells, mesenchymal stem cells, hematopoietic stem cells, skeletal stem cells, and multipotent stem cells, can function to artificially introduce highly regenerative cells into decrepit biological tissues and augment the healing process at the tissue level. Stem cells are molecularly and functionally indistinguishable from standard human tissues. The widespread appeal of stem cell therapy lies in its potential benefits as a therapeutic technology that, if harnessed, can be applied in clinical settings. This review aims to establish the molecular pathophysiology of bone healing and the current stem cell interventions that disrupt or augment the bone healing process and, finally, considers the future direction/therapeutic options related to stem cells and bone healing.

Sensory Nerve Regulation via H3K27 Demethylation Revealed in Akermanite Composite Microspheres Repairing Maxillofacial Bone Defect.

Maxillofacial bone defects exhibit intricate anatomy and irregular morphology, presenting challenges for effective treatment. This study aimed to address these challenges by developing an injectable bioactive composite microsphere, termed D-P-Ak (polydopamine-PLGA-akermanite), designed to fit within the defect site while minimizing injury. The D-P-Ak microspheres biodegraded gradually, releasing calcium, magnesium, and silicon ions, which, notably, not only directly stimulated the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) but also activated sensory nerve cells to secrete calcitonin gene-related peptide (CGRP), a key factor in bone repair. Moreover, the released CGRP enhanced the osteogenic differentiation of BMSCs through epigenetic methylation modification. Specifically, inhibition of EZH2 and enhancement of KDM6A reduced the trimethylation level of histone 3 at lysine 27 (H3K27), thereby activating the transcription of osteogenic genes such as Runx2 and Osx. The efficacy of the bioactive microspheres in bone repair is validated in a rat mandibular defect model, demonstrating that peripheral nerve response facilitates bone regeneration through epigenetic modification. These findings illuminated a novel strategy for constructing neuroactive osteo-inductive biomaterials with potential for further clinical applications.

Technology Behind Cell Therapy Augmentation of Fracture Healing: Concentrated Bone Marrow Aspirate.

With an aging population, and an anticipated increase in overall fracture incidence, a sound understanding of bone healing and how technology can optimize this process is crucial. Concentrated bone marrow aspirate (cBMA) is a technology that capitalizes on skeletal stem and progenitor cells (SSPCs) to enhance the regenerative capacity of bone. This overview highlights the science behind cBMA, discusses the role of SSPCs in bone homeostasis and fracture repair, and briefly details the clinical evidence supporting the use of cBMA in fracture healing. Despite promising early clinical results, a lack of standardization in harvest and processing techniques, coupled with patient variability, presents challenges in optimizing the use of cBMA. However, cBMA remains an emerging technology that may certainly play a crucial role in the future of fracture healing augmentation.

Insights and Advancements in Periodontal Tissue Engineering and Bone Regeneration.

The regeneration of periodontal bone defects continues to be an essential therapeutic concern in dental biomaterials. Numerous biomaterials have been utilized in this sector so far. However, the immune response and vascularity in defect regions may be disregarded when evaluating the effectiveness of biomaterials for bone repair. Among several regenerative treatments, the most recent technique of in situ tissue engineering stands out for its ability to replicate endogenous restorative processes by combining scaffold with particular growth factors. Regenerative medicine solutions that combine biomaterials/scaffolds, cells, and bioactive substances have attracted significant interest, particularly for bone repair and regeneration. Dental stem cells (DSCs) share the same progenitor and immunomodulatory properties as other types of MSCs, and because they are easily isolable, they are regarded as desirable therapeutic agents in regenerative dentistry. Recent research has demonstrated that DSCs sown on newly designed synthetic bio-material scaffolds preserve their proliferative capacity while exhibiting increased differentiation and immuno-suppressive capabilities. As researchers discovered how short peptide sequences modify the adhesion and proliferative capacities of scaffolds by activating or inhibiting conventional osteogenic pathways, the scaffolds became more effective at priming MSCs. In this review, the many components of tissue engineering applied to bone engineering will be examined, and the impact of biomaterials on periodontal regeneration and bone cellular biology/molecular genetics will be addressed and updated.

The Establishment of Calvarial Suture-Bony Composite Defects in Rats: A Standardized Model for Suture-Regenerative Therapy Investigation.

Large-scale calvarial defects often coincide with cranial suture disruption, leading to impairments in calvarial defect restoration and skull development (the latter occurs in the developing cranium). However, the lack of a standardized model hinders progress in investigating suture-regenerative therapies and poses challenges for conducting comparative analyses across distinct studies. To address this issue, the current protocol describes the detailed modeling process of calvarial suture-bony composite defects in rats. The model was generated by drilling full-thickness rectangular holes measuring 4.5 mm × 2 mm across the coronal sutures. The rats were euthanized, and the cranium samples were harvested postoperatively at day 0, week 2, week 6, and week 12. µCT results from samples collected immediately post-surgery confirmed the successful establishment of the suture-bony composite defect, involving the removal of the coronal suture and the adjacent bone tissues. Data from the 6th and 12th postoperative weeks demonstrated a natural healing tendency for the defect to close. Histological staining further validated this trend by showing increased mineralized fibers and new bone at the defect center. These findings indicate progressive suture fusion over time following calvarial defects, underscoring the significance of therapeutic interventions for suture regeneration. We anticipate that this protocol will facilitate the development of suture-regenerative therapies, offering fresh insights into the functional restoration of calvarial defects and reducing adverse outcomes associated with suture loss.

[Autologous platelet concentrates in regenerative dentistry - A narrative literature review. Part II: clinical application of PRF in periodontology and implantology].

The clinical impact of platelet-rich fibrin (PRF) and plasma rich in growth factors (PRGF®) respectively has been studied extensively in the field of regenerative dentistry during the last two decades. Literature supports evidence for additional benefits in regenerative periodontal therapy, alveolar ridge preservation, management of extraction sockets, implantology including guided bone regeneration as well as defect management in oral surgery. Regarding gingival wound healing and soft tissue regeneration, there is sufficient evidence for their positive effects which have been confirmed in several systematic reviews. The effects seem less clear in conjunction with osseous regenerative treatments, where the inter-study heterogenity in terms of different PRF-protocols, indications and application forms might hinder a systematic comparison. Nevertheless there is evidence that PRF might have beneficial effects on hard-tissue or its regeneration respectively.For being able to facilitate conclusions in systematic reviews, precise reporting of the used PRF-protocols is mandatory for future (clinical) research in the field of autologous platelet concentrates.

Evaluation optimum ratio of synthetic bone graft material and platelet rich fibrin mixture in a metal 3D printed implant to enhance bone regeneration.

BACKGROUND: This study aims to evaluate the optimal ratio of synthetic bone graft (SBG) material and platelet rich fibrin (PRF) mixed in a metal 3D-printed implant to enhance bone regeneration. METHODS: Specialized titanium hollow implants (5 mm in diameter and 6 mm in height for rabbit; 6 mm in diameter and 5 mm in height for pig) were designed and manufactured using 3D printing technology. The implants were divided into three groups and filled with different bone graft combinations, namely (1) SBG alone; (2) PRF to SBG in 1:1 ratio; (3) PRF to SBG in 2:1 ratio. These three groups were replicated tightly into each bone defect in distal femurs of rabbits (nine implants, n = 3) and femoral shafts of pigs (fifteen implants, n = 5). Animal tissue sections were obtained after euthanasia at the 8th postoperative week. The rabbit specimens were stained with analine blue, while the pig specimens were stained with Masson-Goldner's trichrome stain to perform histologically examination. All titanium hollow implants were well anchored, except in fracture specimens (three in the rabbit and one fracture in the pig). RESULT: Rabbit specimens under analine blue staining showed that collagen tissue increased by about 20% and 40% in the 1:1 ratio group and the 2:1 ratio group, respectively. Masson-Goldner's trichrome stain results showed that new bone growth increased by 32% in the 1:1 ratio PRF to SBG, while - 8% in the 2:1 ratio group. CONCLUSION: This study demonstrated that placing a 1:1 ratio combination of PRF and SBG in a stabilized titanium 3D printed implant resulted in an optimal increase in bone growth.

The influence of connective tissue grafting on the reconstruction of a missing facial bone wall using immediate implant placement and simultaneous bone reconstruction: a retrospective long-term cohort study.

PURPOSE: This retrospective cohort study evaluates the influence of connective tissue grafts (CTG) on bone regeneration at implant sites with total loss of the buccal bone wall treated with flapless immediate implant placement (IIP) and reconstruction with autogenous bone chips (AB) within a follow-up of up to 13 years. METHODS: Sixty implants were inserted in 55 patients in sites with total loss of the buccal bone wall between 2008 and 2021. The implants were inserted and the buccal gaps were grafted by AB. A subgroup of 34 sites was grafted additionally with CTG using tunnel technique. Primary outcome was the vertical bone regeneration in height and thickness. Secondary outcome parameters were interproximal marginal bone level, recession, soft tissue esthetics (PES), width of keratinized mucosa (KMW) and probing depths (PPD). RESULTS: Mean follow-up period was 60.8 months. In 55 sites a complete vertical bone regeneration was documented. The mean buccal bone level increased by 10.6 mm significantly. The thickness of the buccal bone wall ranged between 1.7 and 1.9 mm, and was significantly thicker in sites without CTG. Interproximal marginal bone level was at implant shoulder level. The mean recession improved significantly by 1.2 mm. In sites with CTG, recessions and PES improved significantly more. CONCLUSIONS: Additional CTG in extraction sites with total buccal bone loss followed by IIP with simultaneous AB grafting led to improved PES and recession, but also to a thinner buccal bone wall compared to sites grafted just with AB.

Multifunctional Nanofibrous Hollow Microspheres for Enhanced Periodontal Bone Regeneration.

Destructive periodontitis destroys alveolar bone and eventually leads to tooth loss. While guided bone regeneration, which is based on creating a physical barrier to hinder the infiltration of epithelial and connective tissues into defect sites, has been widely used for alveolar bone regeneration, its outcomes remain variable. In this work, a multifunctional nanofibrous hollow microsphere (NFHMS) is developed for enhanced alveolar bone regeneration. The NFHMS is first prepared via combining a double emulsification and a thermally induced phase separation process. Next, E7, a short peptide with high specific affinity to bone marrow-derived stem cells (BMSCs), is conjugated onto the surface of NFHMS. After that, bone forming peptide (BFP), a short peptide derived from bone morphology protein 7 is loaded in calcium phosphate (CaP) nanoparticles, which are further encapsulated in the hollow space of the NFHMS-E7 to form NFHMS-E7-CaP/BFP. The NFHMS-E7-CaP/BFP selectively promoted the adhesion of BMSCs and expelled the adhesion of fibroblasts and epithelial cells. In addition, the BFP is sustainedly released from the NFHMS-E7-CaP/BFP to enhance the osteogenesis of BMSCs. A rat challenging fenestration defect model showed that the NFHMS-E7-CaP/BFP significantly enhanced alveolar bone tissue regeneration. This work provides a novel bioengineering approach for guided bone regeneration.

Effect of M2-macrophage treated lymphatic endothelial cells on angiogenesis that promoted osteointegration.

Early vascularization plays an essential role during the whole process in bone regeneration because of the function of secreting cytokines, transporting nutrients and metabolic wastes. As the preliminary basis of bone repair, angiogenesis is regulated by immune cells represented by macrophages to a great extent. However, with the discovery of the endolymphatic circulation system inside bone tissue, the role of vascularization became complicated and confusing. Herein, we developed a macrophage/lymphatic endothelial cells (LECs)/human umbilical vein endothelial cells (HUVECs) co-culture system to evaluate the effect of macrophage treated lymphatic endothelial cells on angiogenesis in vitro and in vivo. In this study, we collected the medium from macrophage (CM) for LECs culture. We found that CM2 could promote the expression of LECs markers and migration ability, which indicated the enhanced lymphogenesis. In addition, the medium from LECs was collected for culturing HUVECs. The CM2-treated LECs showed superior angiogenesis property including the migration capacity and expression of angiogenetic markers, which suggested the superior vascularization. Rat femoral condyle defect model was applied to confirm the hypothesis in vivo. Generally, M2-macrophage treated LECs showed prominent angiogenetic potential coupling with osteogenesis.

A comparative analysis of particulate bovine bone substitutes for oral regeneration: a narrative review.

PURPOSE: Particulate bovine bone substitutes (BS) are commonly used in oral regeneration. However, more literature is needed focusing on comparative analyses among various particulate bovine BS. This study evaluates pre-clinical and clinical data of different particulate bovine BS in oral regeneration. METHODS: A narrative review was conducted by screening the PubMed database Included in the review were pre-clinical and clinical studies until 2024 comparing a minimum of two distinct particulate bovine BS. In addition to examining general data concerning manufacturing and treatment processes, biological safety, physical and chemical characteristics, and graft resorption, particular emphasis was placed on assessing pre-clinical and clinical data related to ridge preservation, sinus floor elevation, peri-implant defects, and various forms of alveolar ridge augmentation utilizing particulate bovine BS. RESULTS: Various treatment temperatures ranging from 300 to 1,250 °C and the employment of chemical cleaning steps were identified for the manufacturing process of particulate bovine BS deemed to possess biosecurity. A notable heterogeneity was observed in the physical and chemical characteristics of particulate bovine BS, with minimal or negligible graft resorption. Variations were evident in particle and pore sizes and the porosity of particulate bovine BS. Pre-clinical assessments noted a marginal inclination towards favorable outcomes for particulate bovine BS subjected to higher treatment temperatures. However, clinical data are insufficient. No distinctions were observed regarding ridge preservation, while slight advantages were noted for high-temperature treated particulate bovine BS in sinus floor elevation. CONCLUSIONS: Subtle variances in both pre-clinical and clinical outcomes were observed in across various particulate bovine BS. Due to inadequate data, numerous considerations related to diverse particulate bovine BS, including peri-implant defects, must be more conclusive. Additional clinical studies are imperative to address these knowledge gaps effectively.