Bioactive nanocomposite hydrogel enhances postoperative immunotherapy and bone reconstruction for osteosarcoma treatment.

Osteosarcoma, a malignant bone tumor often characterized by high hedgehog signaling activity, residual tumor cells, and substantial bone defects, poses significant challenges to both treatment response and postsurgical recovery. Here, we developed a nanocomposite hydrogel for the sustained co-delivery of bioactive magnesium ions, anti-PD-L1 antibody (αPD-L1), and hedgehog pathway antagonist vismodegib, to eradicate residual tumor cells while promoting bone regeneration post-surgery. In a mouse model of tibia osteosarcoma, this hydrogel-mediated combination therapy led to remarkable tumor growth inhibition and hence increased animal survival by enhancing the activity of tumor-suppressed CD8+ T cells. Meanwhile, the implanted hydrogel improved the microenvironment of osteogenesis through long-term sustained release of Mg2+, facilitating bone defect repair by upregulating the expression of osteogenic genes. After 21 days, the expression levels of ALP, COL1, RUNX2, and BGLAP in the Vis-αPD-L1-Gel group were approximately 4.1, 5.1, 5.5, and 3.4 times higher than those of the control, respectively. We believe that this hydrogel-based combination therapy offers a potentially valuable strategy for treating osteosarcoma and addressing the tumor-related complex bone diseases.

Photothermal switch by gallic acid-calcium grafts synthesized by coordination chemistry for sequential treatment of bone tumor and regeneration.

The residual bone tumor and defects which is caused by surgical therapy of bone tumor is a major and important problem in clinicals. And the sequential treatment for irradiating residual tumor and repairing bone defects has wildly prospects. In this study, we developed a general modification strategy by gallic acid (GA)-assisted coordination chemistry to prepare black calcium-based materials, which combines the sequential photothermal therapy of bone tumor and bone defects. The GA modification endows the materials remarkable photothermal properties. Under the near-infrared (NIR) irradiation with different power densities, the black GA-modified bone matrix (GBM) did not merely display an excellent performance in eliminating bone tumor with high temperature, but showed a facile effect of the mild-heat stimulation to accelerate bone regeneration. GBM can efficiently regulate the microenvironments of bone regeneration in a spatial-temporal manner, including inflammation/immune response, vascularization and osteogenic differentiation. Meanwhile, the integrin/PI3K/Akt signaling pathway of bone marrow mesenchymal stem cells (BMSCs) was revealed to be involved in the effect of osteogenesis induced by the mild-heat stimulation. The outcome of this study not only provides a serial of new multifunctional biomaterials, but also demonstrates a general strategy for designing novel blacked calcium-based biomaterials with great potential for clinical use.

Use of autologous micrografts associated with xenogeneic anorganic bone in vertical bone augmentation procedures with Barbell Technique®.

INTRODUCTION: Bidirectional vertical ridge augmentation in the posterior maxilla is very challenging. PURPOSE: To evaluate the regenerative potential of micrografts, derived from periosteum or bone tissue, added to an anorganic xenograft in vertical reconstruction of the posterior maxilla, by a prospective, controlled study. MATERIALS AND METHODS: After clinical selection and the analysis of CBCT scans, 24 posterior maxillary sites, in 19 patients, were treated by using Barbell Technique®. Sites requiring both inlay and onlay reconstruction were enrolled in the study. In the Control Group (CG, n = 8), a xenograft was used in the inlay site and for the onlay site, a 1:1 mix of xenograft and an autograft was used. In Test Group 1 (TG1, n = 8), both inlay and onlay sites were grafted with the xenograft associated with the micrografts derived from periosteum. In Test Group 2 (TG2, n = 8), both inlay and onlay sites were grafted with the xenograft associated with the micrografts derived from bone. Six months after the procedures, CBCT scans were obtained, and bone biopsy samples were harvested during implant placement surgery. The bone specimens were analyzed histomorphometrically, by measuring the percentages of vital mineralized tissue (VMT), non vital mineralized tissue (NVMT) and non mineralized tissue (NMT). Immunohistochemically, the levels of VEGF were categorized by a score approach. RESULTS: Histomorphometric analysis revealed, for the inlay grafts, no significant difference among the groups for VMT, NVMT and NMT. However, for onlay grafts, CG achieved a higher amount of VMT in comparison with TG2, and the opposite occurred for NMT values. In this regard, no statistical difference was observed between CG and TG1. Concerning immunohistochemistry, the VEGF values for CG and TG1 were slightly higher than those obtained by TG2 for both inlay and onlay grafts, but without statistical significance. CBCT analysis showed a similar level of gain for all groups, for both inlay and onlay bone augmentation sites. Clinically, one implant (in CG) within a total of 50 implants installed, had early failure and was replaced after 3 months. All patients received implant supported prosthesis. CONCLUSION: This study indicated that the clinical use of micrograft derived from periosteum may have some potential to increase bone formation in onlay reconstructions, unlike the micrograft derived from bone tissue.

Insight into the role of integrins and integrins-targeting biomaterials in bone regeneration.

Features of the extracellular matrix, along with biochemical factors, have a momentous impress in making genes on and/or off. The interaction of cells and the extracellular matrix is mediated by integrins. Therefore, these molecules have pivotal roles in regulating cell behaviors. Integrins include a group of molecules with a variety of characteristics that can affect different molecular cascades. Considering the importance of these molecules in tissue regeneration after injury, it is necessary to know well the integrins involved in the process of connecting cells to the extracellular matrix in each tissue.With the increase in life expectancy, bone tissue engineering has received more attention from researchers. Integrins are critical components in osteoblast differentiation, survival, and bone mechanotransduction. During osteogenic differentiation in stem cells, specific integrins facilitate multiple signaling pathways through their cytoplasmic domain, leading to the induction of osteogenic differentiation. Also, due to the importance of using biomaterials in bone tissue engineering, efforts have been made to design and use biomaterials with maximum interaction with integrins. Notably, the use of RGD peptide or fibronectin for surface modification is a well-established and commonly employed approach to manipulate integrin activity.This review article looks into integrins' role in bone development and regeneration. It then goes on to explore the complex mechanisms by which integrins contribute to these processes. In addition, this review discusses the use of natural and synthetic biomaterials that target integrins to promote bone regeneration.

Superior bone regenerative properties of carbonate apatite with locational bone-active factors through an inorganic process.

Rapid bone regeneration is crucial for restoring alveolar bone and oral functions following periodontal diseases. However, the development of effective biomedical materials for this purpose remains insufficient. While bone autografts can enhance bone regeneration, they are invasive to healthy areas. Specifically, for alveolar bone regeneration, the implanted material must possess adequate mechanical strength. Moreover, local administration is preferred for older adults, who are a primary target population, to maintain their quality of life. We developed a silica-substituted carbonate apatite (CO3Ap-silica) block as newly bone substitute with a bone growth factor, featuring the major inorganic component of mature bone to enhance bone regeneration. CO3Ap-silica block stimulated the bone remodeling process at the implantation site and demonstrated significantly better bone regeneration compared to currently used carbonate apatite substitutes. Therefore, this new material is expected to advance technologies for restoring occlusal function after periodontal disease.

Tailoring surface stiffness to modulate senescent macrophage immunomodulation: Implications for osteo-/angio-genesis in aged bone regeneration.

The application of biomaterials in bone regeneration is a prevalent clinical practice. However, its efficacy in elderly patients remains suboptimal, necessitating further advancements. While biomaterial properties are known to orchestrate macrophage (MΦ) polarization and local immune responses, the role of biomaterial cues, specifically stiffness, in directing the senescent macrophage (S-MΦ) is still poorly understood. This study aimed to elucidate the role of substrate stiffness in modulating the immunomodulatory properties of S-MΦ and their role in osteo-immunomodulation. Our results demonstrated that employing collagen-coated polyacrylamide hydrogels with varying stiffness values (18, 76, and 295 kPa) as model materials, the high-stiffness hydrogel (295 kPa) steered S-MΦs towards a pro-inflammatory M1 phenotype, while hydrogels with lower stiffness (18 and 76 kPa) promoted an anti-inflammatory M2 phenotype. The immune microenvironment created by S-MΦs promoted the bioactivities of senescent endothelial cells (S-ECs) and senescent bone marrow mesenchymal stem cells BMSCs (S-BMSCs). Furthermore, the M2 S-MΦs, particularly incubated on the 76 kPa hydrogel matrices, significantly enhanced the ability of angiogenesis of S-ECs and osteogenic differentiation of S-BMSCs, which are crucial and interrelated processes in bone healing. This modulation aided in reducing the accumulation of reactive oxygen species in S-ECs and S-BMSCs, thereby significantly contributing to the repair and regeneration of aged bone tissue.

Revolutionizing Bone Regeneration with Grinder-Based Dentin Biomaterial: A Systematic Review.

Bone tissue regeneration is a critical aspect of dental surgery, given the common occurrence of bone resorption leading to alveolar bone defects. The aim of this paper was to conduct a systematic review to provide a comprehensive summary of the evidence regarding the regenerative properties of dentin biomaterial. This systematic review was conducted through comprehensive searches in the PubMed, Scopus, and Web of Science databases, as well as an extensive exploration of the gray literature sources, including WorldCat, The New York Academy of Medicine Library, and Trip Database, following the established PRISMA protocol. Keywords such as tooth, dentin, grinder, and autograft guided the search, with a focus on a standardized procedure involving dentin grinders within laboratory, experimental, and clinical settings. Initially, a pool of 1942 articles was identified with 452 duplicates removed. An additional 1474 articles were excluded for not aligning with the predefined topics, and three more were excluded due to the unavailability of the full text. Ultimately, 13 articles met the strict inclusion criteria and were included in the review. The chemical composition of the dentin particles was similar to natural bone in terms of oxygen, carbon, calcium, phosphorus, sodium, and magnesium content, as well as in terms of the Ca/P ratio. In addition, the dentin also contained amide I and amide II structures, as well as aliphatic and hydroxyl functional groups. The chemically treated dentin was free of microorganisms. The dentin had characteristic tubules that opened after chemical treatment. At the cellular level, dentin released bone morphogenetic protein 2, induced significant cell growth, and stimulated the reorganization of the fibroblast cytoskeleton. Most clinical studies have focused on alveolar bone regeneration. After the transplantation of demineralized dentin particles, studies have observed new bone formation, a reduction in residual bone, and an increase in connective tissue. Clinical reports consistently indicate uncomplicated healing and recovery post-transplantation. However, there is a notable gap in the evidence concerning complication rates, patient-reported outcomes, and the presence of pro-inflammatory factors. In conclusion, dentin biomaterial emerges as a versatile bone substitute, demonstrating high biocompatibility and ease of acquisition. The preservation of its internal structure containing organic matter and growth factors enhances its potential for effective bone regeneration. Particularly, in dental surgery, dentin-derived materials present a promising alternative to traditional autologous bone autografts, offering the potential to reduce patient morbidity and treatment costs.

Osteogenic potentials in canine mesenchymal stem cells: unraveling the efficacy of polycaprolactone/hydroxyapatite scaffolds in veterinary bone regeneration.

BACKGROUND: The integration of stem cells, signaling molecules, and biomaterial scaffolds is fundamental for the successful engineering of functional bone tissue. Currently, the development of composite scaffolds has emerged as an attractive approach to meet the criteria of ideal scaffolds utilized in bone tissue engineering (BTE) for facilitating bone regeneration in bone defects. Recently, the incorporation of polycaprolactone (PCL) with hydroxyapatite (HA) has been developed as one of the suitable substitutes for BTE applications owing to their promising osteogenic properties. In this study, a three-dimensional (3D) scaffold composed of PCL integrated with HA (PCL/HA) was prepared and assessed for its ability to support osteogenesis in vitro. Furthermore, this scaffold was evaluated explicitly for its efficacy in promoting the proliferation and osteogenic differentiation of canine bone marrow-derived mesenchymal stem cells (cBM-MSCs) to fill the knowledge gap regarding the use of composite scaffolds for BTE in the veterinary orthopedics field. RESULTS: Our findings indicate that the PCL/HA scaffolds substantially supported the proliferation of cBM-MSCs. Notably, the group subjected to osteogenic induction exhibited a markedly upregulated expression of the osteogenic gene osterix (OSX) compared to the control group. Additionally, the construction of 3D scaffold constructs with differentiated cells and an extracellular matrix (ECM) was successfully imaged using scanning electron microscopy. Elemental analysis using a scanning electron microscope coupled with energy-dispersive X-ray spectroscopy confirmed that these constructs possessed the mineral content of bone-like compositions, particularly the presence of calcium and phosphorus. CONCLUSIONS: This research highlights the synergistic potential of PCL/HA scaffolds in concert with cBM-MSCs, presenting a multidisciplinary approach to scaffold fabrication that effectively regulates cell proliferation and osteogenic differentiation. Future in vivo studies focusing on the repair and regeneration of bone defects are warranted to further explore the regenerative capacity of these constructs, with the ultimate goal of assessing their potential in veterinary clinical applications.

Macrophage-Centric Biomaterials for Bone Regeneration in Diabetes Mellitus: Contemporary Advancements, Challenges, and Future Trajectories.

Increased susceptibility to bone fragility and the diminution of bone regenerative capacity are recognized as significant and frequent sequelae of diabetes mellitus. Research has elucidated the pivotal role of macrophages in the pathogenesis and repair of diabetic bone defects. Notwithstanding this, the therapeutic efficacy of traditional interventions remains predominantly inadequate. Concomitant with substantial advancements in tissue engineering in recent epochs, there has been an escalation in the development of biomaterials designed to modulate macrophage activity, thereby augmenting osseous tissue regeneration in the context of hyperglycemia. This review amalgamates insights from extant research and delineates recent progressions in the domain of biomaterials that target macrophages for the regeneration of diabetic bone, whilst also addressing the clinical challenges and envisaging future directions within this field.

Barrier Membrane with Janus Function and Structure for Guided Bone Regeneration.

Guided bone regeneration (GBR) technology has been demonstrated to be an effective method for reconstructing bone defects. A membrane is used to cover the bone defect to stop soft tissue from growing into it. The biosurface design of the barrier membrane is key to the technology. In this work, an asymmetric functional gradient Janus membrane was designed to address the bidirectional environment of the bone and soft tissue during bone reconstruction. The Janus membrane was simply and efficiently prepared by the multilayer self-assembly technique, and it was divided into the polycaprolactone isolation layer (PCL layer, GBR-A) and the nanohydroxyapatite/polycaprolactone/polyethylene glycol osteogenic layer (HAn/PCL/PEG layer, GBR-B). The morphology, composition, roughness, hydrophilicity, biocompatibility, cell attachment, and osteogenic mineralization ability of the double surfaces of the Janus membrane were systematically evaluated. The GBR-A layer was smooth, dense, and hydrophobic, which could inhibit cell adhesion and resist soft tissue invasion. The GBR-B layer was rough, porous, hydrophilic, and bioactive, promoting cell adhesion, proliferation, matrix mineralization, and expression of alkaline phosphatase and RUNX2. In vitro and in vivo results showed that the membrane could bind tightly to bone, maintain long-term space stability, and significantly promote new bone formation. Moreover, the membrane could fix the bone filling material in the defect for a better healing effect. This work presents a straightforward and viable methodology for the fabrication of GBR membranes with Janus-based bioactive surfaces. This work may provide insights for the design of biomaterial surfaces and treatment of bone defects.

Investigation of the extent of post-extraction bone contraction and remodeling after 4 months. A prospective pilot study.

OBJECTIVES: To investigate the correlation between the serum levels of 25(OH)D and the resorption of the alveolar bone walls and regeneration of the alveolar space after tooth extraction. METHODS: 14 adults in need of extraction of hopeless teeth were enrolled. An intraoral digital impression was performed, and each patient was tested to assess serum vitamin D levels. Subsequently, extraction of teeth and contextual guided bone regeneration was performed using porcine origin graft material and a resorbable collagen membrane to covert the defect. After 4 months, an impression was taken, and the model was scanned using a professional scanner for lab. At the same time, a cone beam computed tomography was performed to plan implant insertion through fully digital computer guided surgery. Bone was collected to perform histological and histomorphometric analysis. Pre and postoperative scans were compared using a specific software to estimate the volumetric changes. Tests were applied to investigate the relationship between the different predictor variables and the outcome variables. RESULTS: 14 patients were divided in 3 groups depending on the serum Vit-D levels, identifying three ranges corresponding to low (lower than 20), medium (between 20 and 30), and optimal vitamin D levels (higher than 30). Volumetric contraction after extraction was observed for all patients, without any significant difference between the groups. Focusing on the post-extraction regeneration, patients belonging to the group with lower levels of Vit-D displayed lower and more disorganized levels of bone. Immunohistochemistry analysis showed that Col1A1 and Osteocalcin had no physiological alteration. Osteopontin could be identified near the external surface of bone tissue granules. Runx2 signals were detected near the margins of bone trabeculae. CONCLUSIONS: Serum vit-D levels do not appear to influence the extent of post-extraction bone contraction; on the contrary, they seem to influence the post-extraction regeneration. CLINICAL SIGNIFICANCE: Vit D serum levels may influence the regenerative aspect during post-extraction turn-over. This might suggest controlling and (in case of low levels) recommend Vit D supplement in the patient diet in case of extraction.

Liquefied capsules containing nanogrooved microdiscs and umbilical cord-derived cells for bone tissue engineering.

Background: Surface topography has been shown to influence cell behavior and direct stromal cell differentiation into distinct lineages. Whereas this phenomenon has been verified in two-dimensional cultures, there is an urgent need for a thorough investigation of topography's role within a three-dimensional (3D) environment, as it better replicates the natural cellular environment. Methods: A co-culture of Wharton's jelly-derived mesenchymal stem/stromal cells (WJ-MSCs) and human umbilical vein endothelial cells (HUVECs) was encapsulated in a 3D system consisting of a permselective liquefied environment containing freely dispersed spherical microparticles (spheres) or nanogrooved microdiscs (microdiscs). Microdiscs presenting 358 ± 23 nm grooves and 944 ± 49 nm ridges were produced via nanoimprinting of spherical polycaprolactone microparticles between water-soluble polyvinyl alcohol counter molds of nanogrooved templates. Spheres and microdiscs were cultured in vitro with umbilical cord-derived cells in a basal or osteogenic medium within liquefied capsules for 21 days. Results: WJ-MSCs and HUVECs were successfully encapsulated within liquefied capsules containing spheres and microdiscs, ensuring high cellular viability. Results show an enhanced osteogenic differentiation in microdiscs compared to spheres, even in basal medium, evidenced by alkaline phosphatase activity and osteopontin expression. Conclusions: This work suggests that the topographical features present in microdiscs induce the osteogenic differentiation of adhered WJ-MSCs along the contact guidance, without additional differentiation factors. The developed 3D bioencapsulation system comprising topographical features might be suitable for bone tissue engineering approaches with minimum in vitro manipulation.

Lateral Alveolar Ridge Augmentation with Autogenous Tooth Roots and Staged Implant Placement-5-Year Follow-Up Case Series.

Background/Objectives: Alveolar bone augmentation before implant placement is a safe and effective treatment option for the reconstruction of a deficient alveolar ridge. According to recent research, permanent teeth have been used as bone graft materials, with studies confirming their clinical and histological results. This study aimed to evaluate the efficacy of alveolar ridge augmentation with autogenous tooth roots and staged implant placement, and peri-implant tissue stability in augmented sites. Methods: A total of 20 augmentations with autogenous tooth roots on mandibular alveolar ridges in 15 patients were performed. After 6 months, the ridge width (RWa) and ridge width gain (RWg) were measured. Titanium dental implants were placed in grafted sites and loaded 10 weeks after placement. Clinical parameters (bleeding on probing-BOP; probing depth-PD; mucosal recession-MR; and clinical attachment level-CAL) were assessed 2 months (T1), 3 years (T2), and 5 years (T3) after implant loading. Results: The mean RWa was 6.71 ± 0.74 mm, and the RWg was 3.15 ± 0.54 mm, respectively. No statistically significant differences were observed for clinical parameters (BOP, PD, MR, and CAL) among different time points (p > 0.05). Conclusions: Autogenous tooth roots represent a viable solution for alveolar ridge augmentation and implant placement, providing a stable environment for peri implant tissues.

Effectiveness of the Association of Fibrin Scaffolds, Nanohydroxyapatite, and Photobiomodulation with Simultaneous Low-Level Red and Infrared Lasers in Bone Repair.

Biomaterials and biopharmaceuticals for correcting large bone defects are a potential area of translational science. A new bioproduct, purified from snake venom and fibrinogen from buffalo blood, aroused interest in the repair of venous ulcers. Expanding potential uses, it has also been used to form biocomplexes in combination with bone grafts, associated with physical therapies or used alone. The aim of this preclinical study was to evaluate low-level laser photobiomodulation (PBM) in critical defects in the calvaria of rats filled with nanohydroxyapatite (NH) associated with the heterologous fibrin biopolymer (HFB). Sixty animals were used, divided into six groups (n = 10 each): G1 (NH); G2 (HFB); G3 (NH + HFB); G4 (NH + PBM); G5 (HFB + PBM); G6 (NH + HFB + PBM). PBM simultaneously used red (R) and infrared (IR) light emission, applied intraoperatively and twice a week, until the end of the experiment at 42 days. Microtomography, bone formation can be seen initially at the margins of the defect, more evident in G5. Microscopically, bone formation demonstrated immature and disorganized trabeculation at 14 days, with remnants of grafting materials. At 42 days, the percentage of new bone formed was higher in all groups, especially in G5 (HFB, 45.4 ± 3.82), with collagen fibers at a higher degree of maturation and yellowish-green color in the birefringence analysis with Picrosirius-red. Therefore, it is concluded that the HFB + PBM combination showed greater effectiveness in the repair process and presents potential for future clinical studies.

Novel Strategies for Spatiotemporal and Controlled BMP-2 Delivery in Bone Tissue Engineering.

Bone morphogenetic protein-2 (BMP-2) has been commercially approved by the Food and Drug Administration for use in bone defects and diseases. BMP-2 promotes osteogenic differentiation of mesenchymal stem cells. In bone tissue engineering, BMP-2 incorporated into scaffolds can be used for stimulating bone regeneration in organoid construction, drug testing platforms, and bone transplants. However, the high dosage and uncontrollable release rate of BMP-2 challenge its clinical application, mainly due to the short circulation half-life of BMP-2, microbial contamination in bone extracellular matrix hydrogel, and the delivery method. Moreover, in clinical translation, the requirement of high doses of BMP-2 for efficacy poses challenges in cost and safety. Based on these, novel strategies should ensure that BMP-2 is delivered precisely to the desired location within the body, regulating the timing of BMP-2 release to coincide with the bone healing process, as well as release BMP-2 in a controlled manner to optimize its therapeutic effect and minimize side effects. This review highlights improvements in bone tissue engineering applying spatiotemporal and controlled BMP-2 delivery, including molecular engineering, biomaterial modification, and synergistic therapy, aiming to provide references for future research and clinical trials.

Bone augmentation using titanium mesh: A systematic review and meta-analysis.

PURPOSE: To review and compare the available literature on bone regeneration using titanium mesh and map the current evidence on bone gain outcomes and complications while comparing this scaffold with collagen membranes. MATERIALS AND METHODS: A comprehensive electronic and manual search was performed to identify randomised and non-randomised prospective controlled clinical trials that involved the use of titanium mesh in at least one arm, with outcomes including complications and vertical and/or horizontal bone gain. The focused questions were defined as follows: What are the outcomes of using titanium mesh in ridge augmentation compared to other types of barrier membrane, and what is the complication rate (membrane exposure and infection) when titanium mesh is used in these procedures? RESULTS: A total of 22 articles were included in the qualitative analysis. Overall, the studies that measured bone gain resulted in 3.36 mm vertical (196 subjects; 95% confidence interval 2.44 to 4.64 mm, range 1.4 to 5.7 mm) and 3.26 mm horizontal augmentation (81 subjects; 95% confidence interval 2.93 to 3.63 mm, range 2.6 to 3.7 mm), with variability among studies. The most commonly noted complication was mesh exposure, regardless of the type of mesh used, and the second most common was graft failure. The overall pooled complications rate reported in clinical trials was 10.8%. The meta-analysis comparing titanium mesh and collagen membranes, controlling for the type of bone regeneration (staged or simultaneous with implant placement), failed to show a significant difference in horizontal bone gain between the two techniques. CONCLUSIONS: Within the limitations of the present study and acknowledging the heterogeneity among the articles included, titanium mesh can serve as a feasible protective scaffold for bone regeneration with a relatively acceptable complication rate and in defects requiring around 4 mm 3D reconstruction. Data on patient-reported outcomes were scarce. CONFLICT-OF-INTEREST STATEMENT: None of the authors have any financial interests, either directly or indirectly, in the products or information mentioned in the present article.

A randomised controlled trial comparing the effectiveness of guided bone regeneration with polytetrafluoroethylene titanium-reinforced membranes, CAD/CAM semi-occlusive titanium meshes and CAD/CAM occlusive titanium foils in partially atrophic arches.

PURPOSE: To compare the clinical effectiveness of three different devices used in guided bone regeneration procedures for partially atrophic arches. MATERIALS AND METHODS: A randomised controlled trial with three parallel arms was conducted. The study evaluated titanium-reinforced polytetrafluoroethylene membrane (PTFE group), semi-occlusive CAD/CAM titanium mesh (mesh group) and occlusive CAD/CAM titanium foil (foil group) in terms of surgical outcomes and complications as well as surgical times and surgeon satisfaction in 27 guided bone regeneration procedures, presenting results from 1 year post-implant placement. RESULTS: Complications occurred in seven patients. No significant difference was found between the groups in terms of the occurrence of complications (P = 0.51), device exposure (P = 0.12) and implant failure (P = 0.650). Surgeon satisfaction varied significantly, with the PTFE group differing from the mesh (P = 0.003) and foil groups (P 0.001), but not between meshes and foils (P = 0.172). Surgical times also differed significantly, with longer times for PTFE membranes compared to meshes (P 0.001) and foils (P = 0.006), but with no difference between meshes and foils (P = 0.308). The mean reconstructed bone volume was 1269.55 ± 561.08 mm3, with no significant difference observed between the three groups (P = 0.815). There was also no significant difference for mean maximum height (6.72 mm, P = 0.867) and width (7.69 mm, P = 0.998). The mean marginal bone loss at 1 year after implant placement was 0.59 ± 0.27 mm. CONCLUSIONS: Although this study provides valuable insights into the potential benefits of using different types of CAD/CAM devices, further research with larger sample sizes and longer follow-up periods is warranted to validate these findings. CONFLICT-OF-INTEREST STATEMENT: The authors declare there are no conflicts of interest relating to this study.

Hybrid scaffolds for bone tissue engineering: Integration of composites and bioactive hydrogels loaded with hDPSCs.

Bone tissue regeneration remains a significant challenge in clinical settings due to the complexity of replicating the mechanical and biological properties of bone environment. This study addresses this challenge by proposing a hybrid scaffold designed to enhance both bioactivity and physical stability for bone tissue regeneration. This research is the fisrt to develop a rigid 3D structure composed of polycaprolactone (PCL) and hydroxyapatite nanoparticles (nHA) integrated with a bioink containing human dental pulp stem/stromal cells (hDPSCs), alginate, nHA and collagen (Col). The biofabricated constructs were extensively characterized through cytocompatibility tests, osteogenic differentiation assessment, and biocompatibility evaluation in a rat model. In vitro results demontrated that the hybrid scaffolds presented significantly higher cell viability after 168 h compared to the control group. Furthermore, the hybrid scaffolds showed increased osteogenic differentiation relative to other groups. In vivo evaluation indicated good biocompatibility, characterized by minimal inflammatory response and successful tissue integration. These findings highlight the scaffold's potential to support bone tissue regeneration by combining the mechanical strength of PCL and nHA with the biological activity of the alginate-nHA-Col and hDPSCs bioink. The current study provides a promising foundation for the development of biomaterials aimed at improving clinical outcomes in bone repair and regeneration, particulary for the treatment of critical-size bone defects, targeted drug administration, and three-dimensional models for bone tissue engineering.

Multi-functional PEEK implants enhance osseointegration in OVX rat by remodeling the bone immune microenvironment.

Osseointegration is significantly impeded in osteoporotic conditions due to the elevated levels of reactive oxygen species (ROS) and inflammation at the site of injury. To enhance bone regeneration in osteoporotic conditions, a modified polyether ether ketone (PEEK) implants was prepared, denoted as PEEK-PDA-Sr. The implants consisted of mussel adhesion layer with the conjugation of strontium (Sr) ions, which can constantly release Sr ions for up to 3 weeks. PEEK-PDA-Sr demonstrated excellent biocompatibility and effectively regulated intracellular ROS levels and macrophage differentiation. In addition, the PEEK-PDA-Sr facilitated the osteogenesis of bone marrow stromal cells (BMSCs). In the ovariectomized (OVX) rat model of osteoporosis, the PEEK-PDA-Sr exhibited raised osseointegration in the femoral bone defects. The PEEK-PDA-Sr can be used as an immunoregulator with enhanced osseointegration and osteogenesis both in vivo and in vitro, which provides an available approach to treat osteoporotic bone defects.

Guided bone regeneration at dehiscence comparing synthetic bone substitute versus bovine bone mineral: A multicenter, noninferiority, randomized trial.

AIM: To evaluate the efficacy of guided bone regeneration (GBR) for the treatment of peri-implant dehiscence defects using a synthetic bone substitute (SBS) or a deproteinized bovine bone mineral (DBBM) as a bone substitute. METHODS: Patients with expected dehiscence defects following implant placement were randomized to use either SBS or DBBM together with a bioabsorbable collagen membrane over dehiscenced implant surfaces aimed for GBR. The changes in the bone defect size were measured before the GBR procedure and 6 months after implant placement at the re-entry surgery. Secondary outcomes included peri-implant health outcomes, implant cumulative survival rates, bone level changes, and patient-reported outcomes (PROMs) at prosthesis delivery and 1-year follow-up. RESULTS: Of the 49 included patients, 24 were treated with SBS and 25 with DBBM. In the SBS group, the defect height (DH) at implant insertion was 5.1 ± 2.6 mm and was reduced at re-entry to 1.3 ± 2.0 mm (74.5%). In the DBBM group, the respective changes in DH were 4.1 ± 1.7 mm and 1.5 ± 1.9 mm (63.4%). These differences were not statistically significant (p = 0.216). The complete defect resolution rate was also comparable in both groups without statistical difference (62.5% of patients (15/24) vs. 44% of patients (11/25)). Overall, the marginal bone levels remained stable during the 1-year follow-up in both groups. CONCLUSION: The SBS is noninferior to DBBM for simultaneous GBR to implant placement at implant sites with buccal dehiscences in terms of defect resolution and evaluated secondary outcomes (KCT0008393 - this clinical trial was not registered before participant recruitment and randomization).