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.

Pre-vascularized porous gelatin-coated ß-tricalcium phosphate scaffolds for bone regeneration: an in vivo and in vitro investigation.

Vascularization is vital in bone tissue engineering, supporting development, remodeling, and regeneration. Lack of vascularity leads to cell death, necessitating vascularization strategies. Angiogenesis, forming new blood vessels, provides crucial nutrients and oxygen. Pre-vascularized gelatin-coated ß-tricalcium phosphate (G/ß-TCP) scaffolds show promise in bone regeneration and vascularization. Our study evaluates G/ß-TCP scaffolds' osteogenic and angiogenic potential in vitro and a canine model with vascular anastomosis. Channel-shaped G/ß-TCP scaffolds were fabricated using foam casting and sintering of a calcium phosphate/silica slurry-coated polyurethane foam, then coated with cross-linked gelatin. Buccal fat pad-derived stem cells (BFPdSCs) were seeded onto scaffolds and assessed over time for adhesion, proliferation, and osteogenic capacity using scanning electron microscopy (SEM), 4,6-diamidino-2-phenylindole (DAPI) staining, Alamar blue, and alkaline phosphatase (ALP) assays. Scaffolds were implanted in a canine model to evaluate osteogenesis and angiogenesis by histology and CT scans at 12 wk. Our studies showed preliminary results for G/ß-TCP scaffolds supporting angiogenesis and bone regeneration. In vitro analyses demonstrated excellent proliferation/viability, with BFPdSCs adhering and increasing on the scaffolds. ALP activity and protein levels increased, indicating osteogenic differentiation. Examination of tissue samples revealed granulation tissue with a well-developed vascular network, indicating successful angiogenesis and osteogenesis was further confirmed by a CT scan. In vivo, histology revealed scaffold resorption. However, scaffold placement beneath muscle tissue-restricted bone regeneration. Further optimization is needed for bone regeneration applications.

3D-Printed-Cryogel-Impregnated Functionalized Scaffold Augments Bone Regeneration in Critical Tibia Fracture in Goat.

Critical-size bone trauma injuries present a significant clinical challenge because of the limited availability of autografts. In this study, a photocurable composite comprising of polycaprolactone, polypropylene fumarate, and nano-hydroxyapatite (nHAP) (P─P─H) is printed, which shows good osteoconduction in a rat model. A cryogel composed of gelatin-nHAP (GH) is developed to incorporate osteogenic components, specifically bone morphogenetic protein-2 (BMP-2) and zoledronic acid (ZA), termed as GH+B+Z, which is investigated for osteoinductive property in a rat model. Further, a 3D-printed P─P─H scaffold impregnated with GH+B+Z is designed and implanted in a critical-size defect (25 × 10 × 5 mm) in goat tibia. After 4 months, the scaffold is well-integrated with adjacent native bone, with osteoinduction observed in the cryogel-filled region and osteoconduction over the printed scaffold. X-ray radiography and micro-CT analysis showed bone in-growth in the treatment group with 45 ± 1.4% bone volume/tissue volume (BV/TV), while the defect remained unhealed in the control group with BV/TV of 10.5 ± 0.5%. Histology showed significant cell infiltration and matrix deposition over the printed P─P─H scaffold and within the GH cryogel site in the treatment group. Immunohistochemical staining depicted significantly higher normalized collagen I intensity in the treatment group (34.45 ± 2.61%) compared to the control group (4.22 ± 0.78).

Clinical and radiographic changes following transcrestal sinus augmentation: A scoping review of the last 25 years.

INTRODUCTION: Maxillary sinus floor elevation is a surgical procedure intended to increase the volume of the bone vertically to accommodate dental implant placement. This intervention is frequently required for implant installation in the posterior maxilla, where the bone may be insufficient for securing implants of necessary length and stability. Sinus floor elevation can be completed either through a direct approach with a "window" through the lateral wall of the alveolar ridge or an indirect "transcrestal/transalveolar" sinus floor elevation (TSFE), which accesses the sinus floor through the crest of the edentulous ridge. Our study aims to provide a comprehensive scoping review of research conducted over the past 25 years on TSFE, specifically. METHODS: A literature search aimed at identifying pertinent literature for the purpose of this PRISMA-ScR-compliant scoping review was conducted. Only randomized controlled trials, non-randomized controlled trials, prospective cohort studies, and case series that met the eligibility criteria were selected. Relevant data from these studies were extracted. Primary outcome measures included radiographic bone levels and implant failure >5 years. Secondary outcome measures included implant stability at time of placement and complications. Interventions reported in the selected studies were grouped based on treatment modality, which were then compared with the control therapy (traditional osteotome technique) after a minimum of 12 months healing period. RESULTS: Our search yielded 633 records, and after deduplication, 574 of these were screened. Application of the eligibility criteria led to the inclusion of 37 articles in the final selection. Case selection for included studies enrolling subjects: Four different transcrestal sinus elevation treatment modalities were identified: (a) osteotome, (b) piezoelectric surgery, (c) osseodensification, and (d) hydraulic techniques. Due to the heterogeneity of the studies, no superior approach for TSFE could be identified. Overall, all techniques demonstrated high implant survival rates. CONCLUSION: Comprehensive understanding of the patient's medical history, available armamentarium, and post-operative complications/management strategies are all essential to the completion of a successful TSFE approach for implant placement in the posterior maxilla, regardless of the treatment modality used.

The impact of collagen membrane fixation protocols on volume stability in horizontal ridge augmentation in the aesthetic area: A retrospective study.

OBJECTIVES: This study aimed to evaluate the impact of different collagen membran fixation protocols on the volume stability in horizontal ridge augmentation in the aesthetic area. METHODS: A total of 48 patients with 65 augmented sites were included in this study. Implants were placed in the aesthetic region, and simultaneous guided bone regeneration (GBR) surgery was performed for horizontal ridge augmentation. Participants were divided into four groups, each comprising 12 patients, based on different absorbable collagen membrane fixation protocols. Group 1: without fixation; Group 2: fixation with absorbable sutures; Group 3: fixation with titanium pins; Group 4: fixation with titanium pins and absorbable sutures. Cone beam computed tomography (CBCT) was performed immediately after surgery and at 6 months post-surgery, respectively. The horizontal thickness of the augmented region was analyzed for volume stability at the implant shoulder (H0) and 1-5 mm apical to the implant shoulder (H1-H5). Changes in labial thickness during bone healing were calculated as absolute values (mm) and relative values (%). RESULTS: After 6 months of bone healing, horizontal thickness was significantly reduced at all levels (H0-H5) in all groups compared to immediate post-surgery results (p < 0.05). At H1-H5, horizontal bone loss in group 1 was significantly higher than in the other three groups (p < 0.05). Group 4 exhibited significantly less horizontal bone loss compared to group 2 at H0-H2 (p < 0.05) and group 4 compared to group 3 at H0-H1 (p < 0.05). No significant difference in horizontal bone loss between groups 2 and 3 was detected at H0-H5 (p > 0.05). CONCLUSION: Guided bone regeneration in the aesthetic area with additional membrane fixation demonstrated superior volume stability of the augmented region compared to cases without fixation. There was no significant difference in bone volume stability between membrane fixation with titanium pins and fixation with absorbable sutures. However, the combined use of pins and absorbable sutures yielded superior volume stability.

Horizontal Guided Bone Regeneration of the Posterior Mandible to Allow Implant Placement: 1-Year Prospective Study Results.

OBJECTIVE: Assess whether horizontal ridge augmentation with guided bone regeneration (GBR) using deproteinized bovine bone mineral (DBBM), autologous bone, and a resorbable collagen membrane supports successful implant placement. MATERIALS AND METHODS: This open, prospective, single-cohort, multicenter clinical study included patients with ridge defects that required GBR prior to implant insertion. The primary endpoint was radiologically assessed bone gain after 8 months post-GBR, measured at the center of planned implant sites. Secondary endpoints included implant survival and success, marginal bone levels (MBLs), MBL changes, and soft tissue health. RESULTS: Of 45 patients evaluated 8 months post-GBR, nine experienced dehiscence in the first 3 weeks of the healing period. GBR led to radiologically determined mean bone width gain of 4.0 ± 1.5 mm and 4.8 ± 1.7 mm, measured 1 and 3 mm from the top of the crest, respectively, allowing successful implant placement in 44 patients (97.8%). The cumulative implant survival and success rates were 98.9% and 95.5%, respectively. MBLs were stable: -1.18 ± 0.64 mm at definitive prosthesis placement (DPP) and - 1.07 ± 0.74 mm at 1 year. Soft tissue health and esthetics (plaque and bleeding indices, papilla, keratinized mucosa, and pink esthetic score) improved from DPP to 1 year. Patients were highly satisfied with implant function and esthetics, and their oral health-related quality of life improved. CONCLUSIONS: GBR using DBBM and a collagen membrane offered a safe and effective treatment option for horizontal ridge augmentation sufficient to support implant-based tooth rehabilitation. TRIAL REGISTRATION: Registered at ClinicalTrials.gov NCT03028922 (registrations sites, as above listed affiliations, first posted January 23, 2017).

Hypoxia-Mimicking Mediated Macrophage-Elimination of Erythrocytes Promotes Bone Regeneration via Regulating Integrin αvß3/Fe2+-Glycolysis-Inflammation.

Erythrocytes are the dominant component of a blood clot in terms of volume and number. However, longstanding compacted erythrocytes in blood clots form a physical barrier and make fibrin mesh more anti-fibrinolytic, thus impeding infiltration of mesenchymal stem cells. The necrosis or lysis of erythrocytes that are not removed timely can also lead to the release of pro-inflammatory toxic metabolites, interfering with bone regeneration. Proper bio-elimination of erythrocytes is essential for an undisturbed bone regeneration process. Here, hypoxia-mimicking is applied to enhance macrophage-elimination of erythrocytes. The effect of macrophage-elimination of erythrocytes on the macrophage intracellular reaction, bone regenerative microenvironment, and bone regeneration outcome is investigated. Results show that the hypoxia-mimicking agent dimethyloxalylglycine successfully enhances erythrophagocytosis by macrophages in a dose-dependent manner primarily by up-regulating the expression of integrin αvß3. Increased phagocytosed erythrocytes then regulate macrophage intracellular Fe2+-glycolysis-inflammation, creating an improved bone regenerative microenvironment characterized by loose fibrin meshes with down-regulated local inflammatory responses in vivo, thus effectively promoting early osteogenesis and ultimate bone generation. Modulating macrophage-elimination of erythrocytes can be a promising strategy for eradicating erythrocyte-caused bone regeneration hindrance and offers a new direction for advanced biomaterial development focusing on the bio-elimination of erythrocytes.

Graphene Oxide Quantum Dots-Preactivated Dental Pulp Stem Cells/GelMA Facilitates Mitophagy-Regulated Bone Regeneration.

Background: In bone tissue engineering (BTE), cell-laden scaffolds offer a promising strategy for repairing bone defects, particularly when host cell regeneration is insufficient due to age or disease. Exogenous stem cell-based BTE requires bioactive factors to activate these cells. Graphene oxide quantum dots (GOQDs), zero-dimensional derivatives of graphene oxide, have emerged as potential osteogenic nanomedicines. However, constructing biological scaffolds with GOQDs and elucidating their biological mechanisms remain critical challenges. Methods: We utilized GOQDs with a particle size of 10 nm, characterized by a surface rich in C-O-H and C-O-C functional groups. We developed a gelatin methacryloyl (GelMA) hydrogel incorporated with GOQDs-treated dental pulp stem cells (DPSCs). These constructs were transplanted into rat calvarial bone defects to estimate the effectiveness of GOQDs-induced DPSCs in repairing bone defects while also investigating the molecular mechanism underlying GOQDs-induced osteogenesis in DPSCs. Results: GOQDs at 5 µg/mL significantly enhanced the osteogenic differentiation of DPSCs without toxicity. The GOQDs-induced DPSCs showed active osteogenic potential in three-dimensional cell culture system. In vivo, transplantation of GOQDs-preactivated DPSCs/GelMA composite effectively facilitated calvarial bone regeneration. Mechanistically, GOQDs stimulated mitophagy flux through the phosphatase-and-tensin homolog-induced putative kinase 1 (PINK1)/Parkin E3 ubiquitin ligase (PRKN) pathway. Notably, inhibiting mitophagy with cyclosporin A prevented the osteogenic activity of GOQDs. Conclusion: This research presents a well-designed bionic GOQDs/DPSCs/GelMA composite scaffold and demonstrated its ability to promote bone regeneration by enhancing mitophagy. These findings highlight the significant potential of this composite for application in BTE and underscore the crucial role of mitophagy in promoting the osteogenic differentiation of GOQDs-induced stem cells.

Simple-Challenging-Difficult (SCD) Difficulty Classification for Vertical Bone Augmentation.

OBJECTIVE: To propose a new difficulty classification for vertical bone augmentation (VBA) based on different defect morphologies. OVERVIEW: VBA procedures for dental implant placement present significant biological and technical challenges. Among the various techniques, guided bone regeneration (GBR) provides an optimal balance between the anticipated bone gain and the likelihood of postoperative complications. Understanding the specific configuration of defects and adjacent bone peaks is essential for tailoring treatment strategies and improving outcomes. The proposed Simple-Challenging-Difficult (SCD) difficulty classification was based on defect morphology (V-shaped, U-shaped, VV-shaped), including defect size (Height: < 5 mm, 5-8 mm, and > 8 mm), proximity of neighboring bony walls (Width: < 10 mm, 10-20 mm, and > 20 mm), as well as predictability of treatment outcomes. CONCLUSIONS: The proposed difficulty classification for VBA serves as a guide for selecting the most appropriate GBR treatment modality and sequence for safe and predictable management of VBA in implant therapy. In addition, when determining the preferred treatment, it is again essential to consider site-specific and patient-related factors alongside the clinician's surgical experience and skill. CLINICAL SIGNIFICANCE: Identifying defect patterns and bone peak structures is crucial, and the proposed classification assists in decision-making in VBA treatment.

Proanthocyanidins modification of the mineralized collagen scaffold based on synchronous self-assembly/mineralization for bone regeneration.

Proteoglycans (PG) is crucial for regulating collagen formation and mineralization during bone tissue development. A wide variety of PG-modified collagen scaffolds have been proposed for bone engineering application to promote biological responses and work as artificial matrices that guide tissue regeneration. However, poor performance of theses biomaterials against infections has led to an unmet need for clinical prevention. Therefore, we utilized proanthocyanidins (PA) to simulate the functions of PG, including mediating the collagen assembly and intrafibrillar mineralization, to optimize scaffolds performance. The excellent antibacterial properties of PA can endow the scaffolds with anti-infection effects in the process of tissue regeneration. When PA was added during fibrillogenesis, the collagen fibrils appeared irregular aggregation and the mineralization degree was reduced. In contrast, the addition of PA after collagen self-assembly improved the latter's ability to act as a deposition template and remarkably promoted mineral ions infiltration, thus enhancing intrafibrillar mineralization. The PA-modified scaffold displayed a highly hydrophilicity behaviour and long-term resistance to degradation. The sustained release of PA effectively inhibited the activity of Staphylococcus aureus. The scaffold also showed excellent biocompatibility and improved bone regeneration in calvarial critical-size defect models. The application of PA enables a dual-function scaffold with favourable intrafibrillar mineralization and anti-bacterial properties for bone regeneration.

Bifunctional mesoporous HMUiO-66-NH2 nanoparticles for bone remodeling and ROS scavenging in periodontitis therapy.

Periodontal bone defects represent an irreversible consequence of periodontitis associated with reactive oxygen species (ROS). However, indiscriminate removal of ROS proves to be counterproductive for tissue repair and insufficient for addressing existing bone defects. In the treatment of periodontitis, it is crucial to rationally alleviate local ROS while simultaneously promoting bone regeneration. In this study, Zr-based large-pore hierarchical mesoporous metal-organic framework (MOF) nanoparticles (NPs) HMUiO-66-NH2 were successfully proposed as bifunctional nanomaterials for bone regeneration and ROS scavenging in periodontitis therapy. HMUiO-66-NH2 NPs demonstrated outstanding biocompatibility both in vitro and in vivo. Significantly, these NPs enhanced the osteogenic differentiation of bone mesenchymal stem cells (BMSCs) under normal and high ROS conditions, upregulating osteogenic gene expression and mitigating oxidative stress. Furthermore, in vivo imaging revealed a gradual degradation of HMUiO-66-NH2 NPs in periodontal tissues. Local injection of HMUiO-66-NH2 effectively reduced bone defects and ROS levels in periodontitis-induced C57BL/6 mice. RNA sequencing highlighted that differentially expressed genes (DEGs) are predominantly involved in bone tissue development, with notable upregulation in Wnt and TGF-ß signaling pathways. In conclusion, HMUiO-66-NH2 exhibits dual functionality in alleviating oxidative stress and promoting bone repair, positioning it as an effective strategy against bone resorption in oxidative stress-related periodontitis.

An immunomodulatory and osteogenic bacterial cellulose scaffold for bone regeneration via regulating the immune microenvironment.

Creating a bone homeostasis microenvironment that balances osteogenesis and immunity is a substantial challenge for bone regeneration. Here, we prepared an immunomodulatory and osteogenic bacterial cellulose scaffold (FOBS) via a facile one-pot approach. The aldehyde groups were generated via selective oxidation of the hydroxyl groups of bacterial cellulose, offering the bonding sites for dopamine through a Schiff base reaction. At the same time, the deposition of Ca2+ and PO43- was promoted on the aldehyde cellulose scaffold because of the high affinity of the catechol moiety for Ca2+. Compared with that of the unmodified scaffold, the hydroxyapatite content of FOBS increased by 47.1 % according to the ICP results. Interestingly, FOBS regulated the immune microenvironment to accelerate the conversion of M1 to M2 macrophages. The expressions of ARG-1 and Dectin-1 (M2) in the FOBS group increased by >100 %. The expression of osteogenic differentiation of BMSCs was also upregulated. In a rat cranial defect model, the BV/TV of FOBS was significantly increased. Further immunohistochemical analysis revealed that an improved immune microenvironment promoted the osteogenic differentiation of stem cells in vivo. This work provides an effective and easy-to-operate strategy for the development of the bone tissue engineering scaffolds.

Hydraulic sinus floor elevation using advanced platelet-rich fibrin: A randomized clinical trial with two-dimensional radiographic results.

PURPOSE: To assess the radiographic outcomes, complications, and implant survival rates of advanced platelet-rich fibrin versus xenografts in hydraulic sinus floor elevation. METHODS: In this randomized trial, 40 patients with 46 implants were divided into two groups: a test group (advanced platelet-rich fibrin alone) and a control group (xenograft alone). The key outcome measures included bone regeneration, implant survival, and complications. RESULTS: Both groups achieved 100% implant survival. One case of maxillary sinus infection occurred in the control group after surgery. There was no significant difference in bone regeneration between the two groups at 6 months post-surgery and 12 months post-load (P > 0.05). The residual bone height and sinus width at the apex of the implant were significant negative predictors of bone regeneration (P < 0.05), whereas the presence of adjacent teeth was a significant positive predictor (P < 0.05). CONCLUSIONS: Both advanced platelet-rich fibrin and xenografts effectively enhanced bone growth at sinus floor elevation, achieving high implant survival rates over one year. Advanced platelet-rich fibrin alone may be a viable xenograft alternative, necessitating further long-term studies to confirm its efficacy. The study was registered in the Chinese Clinical Trial Registry (http://www.chictr.org.cn/) with the registration number ChiCTR2100042060. This clinical trial was not registered before participant recruitment or randomization.

Magnesium Nanocomposite Hydrogel Reverses the Pathologies to Enhance Mandible Regeneration.

The healing of bone defects after debridement in medication-related osteonecrosis of the jaw (MRONJ) is a challenging medical condition with impaired angiogenesis, susceptible infection, and pro-inflammatory responses. Magnesium (Mg) nanocomposite hydrogel is developed to specifically tackle multiple factors involved in MRONJ. Mg-oxide nanoparticles tune the gelation kinetics in the reaction between N-hydroxysuccinimide-functionalized hyperbranched poly (ethylene glycol) and proteins. This reaction allows an enhanced mechanical property after instant solidification and, more importantly, also stable gelation in challenging environments such as wet and hemorrhagic conditions. The synthesized hydrogel guides mandible regeneration in MRONJ rats by triggering the formation of type H vessels, activating Osterix+ osteoprogenitor cells, and generating anti-inflammatory microenvironments. Additionally, this approach demonstrates its ability to suppress infection by inhibiting specific pathogens while strengthening stress tolerance in the affected alveolar bone. Furthermore, the enhanced osteogenic properties and feasibility of implantation of the hydrogel are validated in mandible defect and iliac crest defect created in minipigs, respectively. Collectively, this study offers an injectable and innovative bone substitute to enhance mandible defect healing by tackling multiple detrimental pathologies.

Anti-aging Metabolite-Based Polymeric Microparticles for Intracellular Drug Delivery and Bone Regeneration.

Alpha-ketoglutarate (AKG), a key component of the tricarboxylic acid (TCA) cycle, has attracted attention for its anti-aging properties. Our recent study indicates that locally delivered cell-permeable AKG significantly promotes osteogenic differentiation and mouse bone regeneration. However, the cytotoxicity and rapid hydrolysis of the metabolite limit its application. In this study, we synthesize novel AKG-based polymeric microparticles (PAKG MPs) for sustained release. In vitro data suggest that the chemical components, hydrophilicity, and size of the MPs can significantly affect their cytotoxicity and pro-osteogenic activity. Excitingly, these biodegradable PAKG MPs are highly phagocytosable for nonphagocytic pre-osteoblasts MC3T3-E1 and primary bone marrow mesenchymal stem cells (BMSCs), significantly promoting their osteoblastic differentiation. RNAseq data suggest that PAKG MPs strongly activate Wnt/ß-catenin and PI3K-Akt pathways for osteogenic differentiation. Moreover, PAKG enables poly (L-lactic acid) and poly (lactic-co-glycolic acid) MPs (PLLA & PLGA MPs) for efficient phagocytosis. Our data indicate that PLGA-PAKG MPs-mediated intracellular drug delivery can significantly promote stronger osteoblastic differentiation compared to PLGA MPs-delivered phenamil. Notably, PAKG MPs significantly improve large bone regeneration in a mouse cranial bone defect model. Thus, the novel PAKG-based MPs show great promise to improve osteogenic differentiation, bone regeneration, and enable efficient intracellular drug delivery for broad regenerative medicine.

Osseointegration of Anodized vs. Sandblasted Implant Surfaces in a Guided Bone Regeneration Acute Dehiscence-Type Defect: An In Vivo Experimental Mandibular Minipig Model.

OBJECTIVES: This controlled preclinical study analyzed the effect of implant surface characteristics on osseointegration and crestal bone formation in a grafted dehiscence defect minipig model. MATERIAL AND METHODS: A standardized 3 mm × 3 mm acute-type buccal dehiscence minipig model grafted with deproteinized bovine bone mineral and covered with a porcine collagen membrane after 2 and 8 weeks of healing was utilized. Crestal bone formation was analyzed histologically and histomorphometrically to compare three implant groups: (1) a novel, commercially available, gradient anodized (NGA) implant, to two custom-made geometric replicas of implant "1," (2) a superhydrophilic micro-rough large-grit sandblasted and acid-etched surface, and (3) a relatively hydrophobic micro-rough large-grit sandblasted and acid-etched surface. RESULTS: At 2 and 8 weeks, there was no difference between the amount and height of newly formed bone (NBH, new bone height; BATA, bone area to total area) for any of the groups (p > 0.05). First bone-to-implant contact (fBIC) and vertical bone creep (VBC) at 2 and 8 weeks were significantly increased for Groups 2 and 3 compared to Group 1 (p < 0.05). At 8 weeks, osseointegration in the dehiscence (dehiscence bone-implant-contact; dBIC) was significantly higher for Groups 2 and 3 compared to Group 1 (p < 0.05). CONCLUSIONS: The amount of newly formed bone (BATA) and NBH was not influenced by surface type. However, moderately rough surfaces demonstrated significantly superior levels of osseointegration (dBIC) and coronal bone apposition (fBIC) in the dehiscence defect compared to the NGA surface at 2 and 8 weeks. TRIAL REGISTRATION: For this type of study, clinical trial registration is not required. This study was conducted at the Biomedical Department of Lund University (Lund, Sweden) and approved by the local Ethics Committee of the University (M-192-14).

Repairing Dehiscence Defects at Implant Sites using ß-Tricalcium Phosphate/Calcium Sulfate versus Xenograft Combined With Membrane: A Randomized Clinical Trial.

Guided bone regeneration (GBR) typically involves bone grafts and a membrane to enhance bone formation. Beta-tricalcium phosphate calcium sulfate (ß-TCP/CS) is a novel material with self-hardening and tissue growth inhibition properties and can potentially replace the need for a membrane. This study compares ß-TricalciumPhosphate/CalciumSulfate with deproteinized bovine bone mineral and a collagen membrane (DBBM/CM) to repair bone defects at implant sites over six months. Sixteen implant defects were divided into ß-TCP/CS (n = 8) and DBBM/CM (n = 8). The results showed no significant differences in vertical and horizontal defect fill in millimeters between ß-TCP/CS (2.87±1.25 and 2.37±1.06 mm., respectively) and DBBM/CM (3.5±0.92 and 2.87±1.12 mm. , respectively). Buccal bone thickness (BT) alterations at the implant platform levels (BT0) were similar for both materials. However, ß-TCP/CS exhibited greater bone alteration at the 2-mm level (BT2: -1.85 mm vs. -0.47 mm) and 4-mm level (BT4: -1.79 mm vs. 0.12 mm) apical to the implant platform compared to DBBM/CM. When assessing volume alteration, ß-TCP/CS showed a significantly greater reduction at the platform to the 2 mm level (-61.98% vs. -23.76%) than DBBM/CM. In conclusion, ß-TCP/CS demonstrated promise for treating buccal bone defects around implants but exhibited higher graft reduction. This suggests that while ß-TricalciumPhosphate/CalciumSulfate may offer clinical benefits, its potential for greater graft reduction should be considered. Further research and evaluation are warranted to fully understand the long-term implications of using ß-TCP/CS in guided bone regeneration procedures.

Mechanical Properties, Microstructure, Degradation Behavior, and Biocompatibility of Zn-0.5Ti-0.5Fe and Zn-0.5Ti-0.5Mg Guided Bone Regeneration Barrier Membranes Prepared Using a Powder Metallurgy Method.

Pure zinc exhibits low mechanical properties, making it unsuitable for use in guided bone regeneration (GBR) membranes. The present study focused on the preparation of Zn alloy GBR films using powder metallurgy, resulting in Zn-0.5Ti-0.5Fe and Zn-0.5Ti-0.5Mg alloy GBR films. The tensile strength of the pure Zn GBR film measured 85.9 MPa, while an elongation at break was 13.5%. In contrast, Zn-0.5Ti-0.5Fe and Zn-0.5Ti-0.5Mg alloy GBR films demonstrated significantly higher tensile strengths of 145.3 and 164.4 MPa, respectively, whereas elongations at break were 30.2% and 19.3%. The addition of Ti, Fe, and Mg substantially enhanced the mechanical properties of the zinc alloys. Corrosion analysis revealed that Zn-0.5Ti-0.5Fe and Zn-0.5Ti-0.5Mg alloy GBR membranes exhibited corrosion potentials of -1.298 and -1.316 V, respectively, with corresponding corrosion current densities of 12.11 and 13.32 µA/cm2. These values were translated to corrosion rates of 0.181 and 0.199 mm/year, indicating faster corrosion rates compared to pure Zn GBR membranes, which displayed a corrosion rate of 0.108 mm/year. Notably, both Zn-based alloy GBR membranes demonstrated excellent cytocompatibility, with a cytotoxicity rating of 0-1 in 25% leachate. Additionally, these membranes exhibited favorable osteogenic ability, as evidenced by the quantitative bone volume/tissue volume ratios (BV/TV) of new bone formation, which reached 30.3 ± 1.4% and 65.5 ± 1.8% for the Zn-0.5Ti-0.5Fe and Zn-0.5Ti-0.5Mg alloy GBR membranes, respectively, after 12 weeks of implantation. These results highlighted the significant potential for facilitating new bone growth. The proposed Zn-0.5Ti-0.5Fe and Zn-0.5Ti-0.5Mg alloy GBR membranes showed promise as viable biodegradable materials for future clinical studies.

Shape Memory Polymer Bioglass Composite Scaffolds Designed to Heal Complex Bone Defects.

An off-the-shelf scaffold with requisite properties could enable the viable treatment of irregular craniomaxillofacial bone defects. Notably, the scaffold should be conformally fitting, innately bioactive, and bioresorbable. In prior work, we developed a series of shape memory polymer (SMP) scaffolds based on cross-linked poly(ε-caprolactone) (PCL). These were capable of "self-fitting" into complex bone defects when exposed to temperatures above the melt transition of the constituent PCL, either linear-PCL-diacrylate (linear-PCL-DA, Tm ∼55 °C) or star-PCL-tetraacrylate (star-PCL-TA, Tm ∼45 °C) for the potential to improve tissue safety. To achieve favorably increased degradation rates versus PCL-only scaffolds, semi-interpenetrating networks (semi-IPNs) were formed by including linear- or star-poly(l-lactic acid) (PLLA). A potential limitation of these self-fitting scaffolds is the lack of bioactivity, which is essential to osteoinductivity and osseointegration. Herein, analogous composite scaffolds were formed with 45S5 bioglass (BG) to impart bioactivity. The solvent-cast particulate leaching fabrication method was adapted to introduce BG to the fused salt template, resulting in composites with BG concentrated on the pore wall surfaces rather than within pore struts. Composite scaffolds with good pore wall integrity were produced with 2.5, 5, and 10 wt % BG. All composite scaffolds exhibited non-brittle behavior and did not fracture with 85% strain. For semi-IPN composite scaffolds, PLLA crystallinity was lost, and mechanical properties were not appreciably altered versus the non-BG controls. Sufficient retention of PCL crystallinity led to excellent shape memory behavior. The inclusion of 5 and 10 wt % BG led to hydroxyapatite mineralization after 1 day of exposure to simulated body fluid, as well as increased rates of in vitro degradation.