Programmed surface platform orchestrates anti-bacterial ability and time-sequential bone healing for implant-associated infection.

Implant-associated infection (IAI) has become an intractable challenge in clinic. The healing of IAI is a complex physiological process involving a series of spatiotemporal connected events. However, existing titanium-based implants in clinic suffer from poor antibacterial effect and single function. Herein, a versatile surface platform based on the presentation of sequential function is developed. Fabrication of titania nanotubes and poly-γ-glutamic acid (γ-PGA) achieves the efficient incorporation of silver ions (Ag+) and the pH-sensitive release in response to acidic bone infection microenvironment. The optimized PGA/Ag platform exhibits satisfactory biocompatibility and converts macrophages from pro-inflammatory M1 to pro-healing M2 phenotype during the subsequent healing stage, which creates a beneficial osteoimmune microenvironment and promotes angio/osteogenesis. Furthermore, the PGA/Ag platform mediates osteoblast/osteoclast coupling through inhibiting CCL3/CCR1 signaling. These biological effects synergistically improve osseointegration under bacterial infection in vivo, matching the healing process of IAI. Overall, the novel integrated PGA/Ag surface platform proposed in this study fulfills function cascades under pathological state and shows great potential in IAI therapy.

Exosomal non-coding RNAs: Emerging insights into therapeutic potential and mechanisms in bone healing.

Exosomes are nano-sized extracellular vesicles (EVs) released by diverse types of cells, which affect the functions of targeted cells by transporting bioactive substances. As the main component of exosomes, non-coding RNA (ncRNA) is demonstrated to impact multiple pathways participating in bone healing. Herein, this review first introduces the biogenesis and secretion of exosomes, and elucidates the role of the main cargo in exosomes, ncRNAs, in mediating intercellular communication. Subsequently, the potential molecular mechanism of exosomes accelerating bone healing is elucidated from the following four aspects: macrophage polarization, vascularization, osteogenesis and osteoclastogenesis. Then, we systematically introduce construction strategies based on modified exosomes in bone regeneration field. Finally, the clinical trials of exosomes for bone healing and the challenges of exosome-based therapies in the biomedical field are briefly introduced, providing solid theoretical frameworks and optimization methods for the clinical application of exosomes in orthopedics.

Do NSAIDs affect bone healing rate, delay union, or cause non-union: an updated systematic review and meta-analysis.

Introduction: Nonsteroidal anti-inflammatory drugs (NSAIDs) may potentially delay or cause non-union of fractures by inhibiting prostaglandin synthesis. However, studies have shown conflicting results. This systematic review and meta-analysis aim to synthesize current evidence on the potential influence of NSAIDs on bone healing. Methods: We conducted a comprehensive search of PubMed, Embase, and Cochrane CENTRAL databases for studies published up to 25 July 2023. Specific keywords included "NSAID," "nonsteroidal anti-inflammatory drug," "cyclooxygenase-2 inhibitor," "bone healing," "non-union," "pseudoarthrosis," "delayed union," and "atrophic bone." Eligible studies included prospective, retrospective, and case-controlled studies assessing the correlation between NSAID use and bone healing outcomes. The leave-one-out approach was used to test the robustness of the meta-analysis results. Results: A total of 20 studies with 523,240 patients were included in the analysis. The mean patient age ranged from 6.7 to 77.0 years, with follow-up durations from 3 to 67 months. The meta-analysis revealed no significant difference in non-union or delayed union between NSAID users and non-users [pooled adjusted odds ratio (OR) = 1.11; 95% confidence interval (CI): 0.99-1.23]. Initial analysis identified a significant association between NSAID usage and an increased risk of reoperation, but this association became insignificant upon sensitivity analysis (crude OR = 1.42; 95% CI: 0.88-2.28). Discussion: NSAIDs may have a minimal impact on non-union or delayed union risks. However, caution is advised due to the limited number of studies and the absence of a specific focus on NSAID types and dosages. Further research is necessary to better understand the implications of NSAID use on bone healing.

Microwave Technique for Linear Skull Fracture Detection-Simulation and Experimental Study Using Realistic Human Head Models.

Microwave (MW) sensing is regarded as a promising technique for various medical monitoring and diagnostic applications due to its numerous advantages and the potential to be developed into a portable device for use outside hospital settings. The detection of skull fractures and the monitoring of their healing process would greatly benefit from a rapidly and frequently usable application that can be employed outside the hospital. This paper presents a simulation- and experiment-based study on skull fracture detection with the MW technique using realistic models for the first time. It also presents assessments on the most promising frequency ranges for skull fracture detection within the Industrial, Scientific and Medical (ISM) and ultrawideband (UWB) ranges. Evaluations are carried out with electromagnetic simulations using different head tissue layer models corresponding to different locations in the human head, as well as an anatomically realistic human head simulation model. The measurements are conducted with a real human skull combined with tissue phantoms developed in our laboratory. The comprehensive evaluations show that fractures cause clear differences in antenna and channel parameters (S11 and S21). The difference in S11 is 0.1-20 dB and in S21 is 0.1-30 dB, depending on the fracture width and location. Skull fractures with a less than 1 mm width can be detected with microwaves at different fracture locations. The detectability is frequency dependent. Power flow representations illustrate how fractures impact on the signal propagation at different frequencies. MW-based detection of skull fractures provides the possibility to (1) detect fractures using a safe and low-cost portable device, (2) monitor the healing-process of fractures, and (3) bring essential information for emerging portable MW-based diagnostic applications that can detect, e.g., strokes.

Decoding Cold Therapy Mechanisms of Enhanced Bone Repair through Sensory Receptors and Molecular Pathways.

Applying cold to a bone injury can aid healing, though its mechanisms are complex. This study investigates how cold therapy impacts bone repair to optimize healing. Cold was applied to a rodent bone model, with the physiological responses analyzed. Vasoconstriction was mediated by an increase in the transient receptor protein channels (TRPs), transient receptor potential ankyrin 1 (TRPA1; p = 0.012), and transient receptor potential melastatin 8 (TRPM8; p < 0.001), within cortical defects, enhancing the sensory response and blood flow regulation. Cold exposure also elevated hypoxia (p < 0.01) and vascular endothelial growth factor expression (VEGF; p < 0.001), promoting angiogenesis, vital for bone regeneration. The increased expression of osteogenic proteins peroxisome proliferator-activated receptor gamma coactivator (PGC-1α; p = 0.039) and RNA-binding motif protein 3 (RBM3; p < 0.008) suggests that the reparative processes have been stimulated. Enhanced osteoblast differentiation and the presence of alkaline phosphatase (ALP) at day 5 (three-fold, p = 0.021) and 10 (two-fold, p < 0.001) were observed, along with increased osteocalcin (OCN) at day 10 (two-fold, p = 0.019), indicating the presence of mature osteoblasts capable of mineralization. These findings highlight cold therapy's multifaceted effects on bone repair, offering insights for therapeutic strategies.

A comparative analysis of postoperative morbidity and alveolar bone regeneration following surgical extraction of impacted lower third molar teeth using piezosurgery and conventional instruments: a split-mouth clinical investigation.

BACKGROUND-OBJECTIVE(S): This randomized, split-mouth study aimed to compare postoperative complications following the surgical extraction of impacted lower third molars using piezosurgery versus conventional rotary instruments. MATERIALS AND METHODS: Twenty-one patients, aged 18-35 years, with bilaterally and symmetrically impacted lower third molars, were randomly assigned to undergo extraction using piezosurgery on one side and conventional rotary instruments on the other. RESULTS: The piezosurgery method required a longer operation time. However, it resulted in quicker resolution of postoperative swelling by the 7th day compared to the conventional method, where swelling persisted longer. Mandibular angle-tragus measurements were significantly higher with the conventional method on the 1st, 3rd, and 7th postoperative days. Although mouth opening decreased significantly after piezosurgery, it returned to preoperative levels by the 7th day, outperforming the conventional method. Postoperative pain was notably higher with the conventional method during the first four days but showed no significant difference from the 5th day onward. Alveolar bone healing was significantly better with piezosurgery at the 3rd and 6th months. Temporary paresthesia occurred in one patient from the conventional group, resolving within four weeks. Neither method resulted in alveolar osteitis. CONCLUSION(S): Within the study's limitations, piezosurgery demonstrated a reduction in postoperative discomfort, suggesting its advantage in enhancing patient recovery following lower third molar extractions. CLINICAL SIGNIFICANCE: Piezosurgery, when used appropriately, can reduce postoperative complications compared to conventional methods. Clinicians should be aware of its indications, benefits, and potential challenges. Trial registration This study was registered as a clinical trial to the ClinicalTrials.gov, and the registration ID is NCT06262841 ( https://clinicaltrials.gov/study/NCT06262841 ).

Systemic Factors Affecting Healing in Dentistry.

Healing process in the oral cavity is influenced by a range of systemic factors. More specifically, patient health status, medications, habits, and nutritional state play crucial roles in dental healing. Additionally, the body's immune response, inflammation, and overall well-being are key determinants in wound repair. Understanding these systemic factors is essential for dental professionals to optimize patient care, minimize complications, and achieve successful healing.

Minimizing Invasiveness in Neurosurgical Osteotomies: A Comparative Histomorphometric Study of Piezoelectric Craniotomy versus High-Speed Drill.

BACKGROUND: Piezoelectric bone cutting has gained popularity in neurosurgical osteotomies due to perceived lower trauma compared to rotary instruments. However, histological confirmation of its decreased aggressiveness is lacking, hindering conclusive proof. This study compares the bony and neuro-meningeal invasiveness of piezoelectric craniotomy with high-speed drill techniques. METHODS: Histological data from 21 sheep undergoing piezoelectric craniotomy and 19 sheep subjected to high-speed electric drill craniotomy were compared. Piezoelectric craniotomy utilized a 0.35 mm micro saw titanium nitride coated. Outcome parameters included the detection of the "smear layer," average osteoblast count per high-power field, and residual bone matrix for bony invasiveness assessment. Parameters for meningeal and brain parenchymal invasiveness included pachymeningeal and leptomeningeal injury, gliosis, and histiocytic infiltration. Statistical significance was determined at P < 0.05. RESULTS: Results showed the Piezo group had fewer frequent smear layers (P <0.001), higher residual bone matrix (P < 0.05), and greater osteoblast counts per high-power field (P < 0.05). Additionally, the Piezo group exhibited lower rates of leptomeningeal injury, cerebral gliosis, and histiocytic infiltration (P < 0.05). CONCLUSIONS: Piezoelectric craniotomy preserves residual osteoblast viability and leptomeningeal integrity while demonstrating lower rates of thermally induced gliosis and histiocytic infiltration compared to high-speed drills. This suggests the piezoelectric osteotome's minimal invasiveness in bone, meningeal, and brain tissue.

Beyond bone volume: Understanding tissue-level quality in healing of maxillary vs. femoral defects.

Currently, principles of tissue engineering and implantology are uniformly applied to all bone sites, disregarding inherent differences in collagen, mineral composition, and healing rates between craniofacial and long bones. These differences could potentially influence bone quality during the healing process. Evaluating bone quality during healing is crucial for understanding local mechanical properties in regeneration and implant osseointegration. However, site-specific changes in bone quality during healing remain poorly understood. In this study, we assessed newly formed bone quality in sub-critical defects in the maxilla and femur, while impairing collagen cross-linking using ß-aminopropionitrile (BAPN). Our findings revealed that femoral healing bone exhibited a 73 % increase in bone volume but showed significantly greater viscoelastic and collagen changes compared to surrounding bone, leading to increased deformation during long-term loading and poorer bone quality in early healing. In contrast, the healing maxilla maintained equivalent hardness and viscoelastic constants compared to surrounding bone, with minimal new bone formation and consistent bone quality. However, BAPN-impaired collagen cross-linking induced viscoelastic changes in the healing maxilla, with no further changes observed in the femur. These results challenge the conventional belief that increased bone volume correlates with enhanced tissue-level bone quality, providing crucial insights for tissue engineering and site-specific implant strategies. The observed differences in bone quality between sites underscore the need for a nuanced approach in assessing the success of regeneration and implant designs and emphasize the importance of exploring site-specific tissue engineering interventions. STATEMENT OF SIGNIFICANCE: Accurate measurement of bone quality is crucial for tissue engineering and implant therapies. Bone quality varies between craniofacial and long bones, yet it's often overlooked in the healing process. Our study is the first to comprehensively analyze bone quality during healing in both the maxilla and femur. Surprisingly, despite significant volume increase, femur healing bone had poorer quality compared to the surrounding bone. Conversely, maxilla healing bone maintained consistent quality despite minimal bone formation. Impaired collagen diminished maxillary healing bone quality, but had no further effect on femur bone quality. These findings challenge the notion that more bone volume equals better quality, offering insights for improving tissue engineering and implant strategies for different bone sites.

Circadian Rhythm-Regulated ADSC-Derived sEVs and a Triphasic Microneedle Delivery System to Enhance Tendon-to-Bone Healing.

Modulating the inflammatory microenvironment to reconstruct the fibrocartilaginous layer while promoting tendon repair is crucial for enhancing tendon-to-bone healing in rotator cuff repair (RCR), a persistent challenge in orthopedics. Small extracellular vesicles (sEVs) hold significant potential to modulate inflammation, yet the efficient production of highly bioactive sEVs remains a substantial barrier to their clinical application. Moreover, achieving minimally invasive local delivery of sEVs to the tendon-to-bone interface presents significant technical difficulties. Herein, the circadian rhythm of adipose-derived stem cells is modulated to increase the yield and enhance the inflammatory regulatory capacity of sEVs. Circadian rhythm-regulated sEVs (CR-sEVs) enhance the cyclic adenosine monophosphate signaling pathway in macrophage (Mφ) via platelet factor 4 delivery, thereby inhibiting Mφ M1 polarization. Subsequently, a triphasic microneedle (MN) scaffold with a tip, stem, and base is designed for the local delivery of CR-sEVs (CR-sEVs/MN) at the tendon-to-bone junction, incorporating tendon-derived decellularized extracellular matrix in the base to facilitate tendon repair. CR-sEVs/MN mitigates inflammation, promotes fibrocartilage regeneration, and enhances tendon healing, thereby improving biomechanical strength and shoulder joint function in a rat RCR model. Combining CR-sEVs with this triphasic microneedle delivery system presents a promising strategy for enhancing tendon-to-bone healing in clinical settings.

Clinical management and innovation in fracture non-union.

INTRODUCTION: With the introduction and continuous improvement in operative fracture fixation, even the most severe bone fractures can be treated with a high rate of successful healing. However, healing complications can occur and when healing fails over prolonged time, the outcome is termed a fracture non-union. Non-union is generally believed to develop due to inadequate fixation, underlying host-related factors, or infection. Despite the advancements in fracture fixation and infection management, there is still a clear need for earlier diagnosis, improved prediction of healing outcomes and innovation in the treatment of non-union. AREAS COVERED: This review provides a detailed description of non-union from a clinical perspective, including the state of the art in diagnosis, treatment, and currently available biomaterials and orthobiologics.Subsequently, recent translational development from the biological, mechanical, and infection research fields are presented, including the latest in smart implants, osteoinductive materials, and in silico modeling. EXPERT OPINION: The first challenge for future innovations is to refine and to identify new clinical factors for the proper definition, diagnosis, and treatment of non-union. However, integration of in vitro, in vivo, and in silico research will enable a comprehensive understanding of non-union causes and correlations, leading to the development of more effective treatments.

Bone healing under different lay-up configuration of carbon fiber-reinforced PEEK composite plates.

Secondary healing of fractured bones requires an application of an appropriate fixator. In general, steel or titanium devices are used mostly. However, in recent years, composite structures arise as an attractive alternative due to high strength to weight ratio and other advantages like, for example, radiolucency. According to Food and Drug Administration (FDA), the only unidirectionally reinforced composite allowed to be implanted in human bodies is carbon fiber (CF)-reinforced poly-ether-ether-ketone (PEEK). In this work, the healing process of long bone assembled with CF/PEEK plates with cross- and angle-ply lay-up configurations is studied in the framework of finite element method. The healing is simulated by making use of the mechanoregulation model basing on the Prendergast theory. Cells transformation is determined by the octahedral shear strain and interstitial fluid velocity. The process runs iteratively assuming single load cycle each day. The fracture is subjected to axial and transverse forces. In the computations, the Abaqus program is used. It is shown that the angle-ply lamination scheme of CF/PEEK composite seems to provide better conditions for the transformation of the soft callus into the bone tissue.

A 3D-printed scaffold composed of Alg/HA/SIS for the treatment of diabetic bone defects.

Background: Diabetic bone healing remains a great challenge due to its pathological features including biochemical disturbance, excessive inflammation, and reduced blood vessel formation. In previous studies, small intestine submucosa (SIS) has been demonstrated for its immunomodulatory and angiogenic properties, which are necessary to diabetic bone healing. However, the noticeable drawbacks of SIS such as fast degradation rate, slow gelling time, and weak mechanical property seriously impede the 3D printing of SIS for bone repair. Method: In this study, we developed a novel kind of 3D-printed scaffold composed of alginate, nano-hydroxyapatite, and SIS. The morphological characterization, biocompatibility, and in vitro biological effects of the scaffolds were evaluated, and an established diabetic rat model was used for testing the in vivo biological effect of the scaffold after implantation. Results: The in vitro and in vivo results show that the addition of SIS can tune the immunomodulatory properties and angiogenic and osteogenic performances of 3D-printed scaffold, where the macrophages polarization of M2 phenotype, migration and tube formation of HUVECs, as well as osteogenic expression of ALP, are all improved, which bode well with the functional requirements for treating diabetic bone nonunion. Furthermore, the incorporation of alginate substantially improves the printability of composites with tunable degradation properties, thereby broadening the application prospect of SIS-based materials in the field of tissue engineering. Conclusion: The fabricated 3D-printed Alg/HA/SIS scaffold provides desirable immunomodulatory effect, as well as good osteogenic and angiogenic performances in vitro and in vivo, which properties are well-suited with the requirement for treating diabetic bone defects. Translational potential of this article: The incorporation of SIS and alginate acid not only provides good printability of the newly fabricated 3D-printed Alg/HA/SIS scaffold, but also improves its immunoregulatory and angiogenic properties, which suits well with the requirement for treating diabetic bone disease and opens up new horizons for the development of implants associating diabetic bone healings.

Structure, ingredient, and function-based biomimetic scaffolds for accelerated healing of tendon-bone interface.

Background: Tendon-bone interface (TBI) repair is slow and challenging owing to its hierarchical structure, gradient composition, and complex function. In this work, enlightened by the natural characteristics of TBI microstructure and the demands of TBI regeneration, a structure, composition, and function-based scaffold was fabricated. Methods: The biomimetic scaffold was designed based on the "tissue-inducing biomaterials" theory: (1) a porous scaffold was created with poly-lactic-co-glycolic-acid, nano-hydroxyapatite and loaded with BMP2-gelatinmp to simulate the bone (BP); (2) a hydrogel was produced from sodium alginate, type I collagen, and loaded with TGF-ß3 to simulate the cartilage (CP); (3) the L-poly-lactic-acid fibers were oriented to simulate the tendon (TP). The morphology of tri-layered constructs, gelation kinetics, degradation rate, release kinetics and mechanical strength of the scaffold were characterized. Then, bone marrow mesenchymal stem cells (MSCs) and tenocytes (TT-D6) were cultured on the scaffold to evaluate its gradient differentiation inductivity. A rat Achilles tendon defect model was established, and BMSCs seeded on scaffolds were implanted into the lesionsite. The tendon-bone lesionsite of calcaneus at 4w and 8w post-operation were obtained for gross observation, radiological evaluation, biomechanical and histological assessment. Results: The hierarchical microstructures not only endowed the scaffold with gradual composition and mechanical properties for matching the regional biophysical characteristics of TBI but also exhibited gradient differentiation inductivity through providing regional microenvironment for cells. Moreover, the scaffold seeded with cells could effectively accelerate healing in rat Achilles tendon defects, attributable to its enhanced differentiation performance. Conclusion: The hierarchical scaffolds simulating the structural, compositional, and cellular heterogeneity of natural TBI tissue performed therapeutic effects on promoting regeneration of TBI and enhancing the healing quality of Achilles tendon. The translational potential of this article: The novel scaffold showed the great efficacy on tendon to bone healing by offering a structural and compositional microenvironment. The results meant that the hierarchical scaffold with BMSCs may have a great potential for clinical application.

Bone Regeneration of Rat Critical-Sized Calvarial Defects by the Combination of Photobiomodulation and Adipose-Derived Mesenchymal Stem Cells.

Introduction: This study explored the synergistic effects of low-level laser therapy (LLLT) and adipose-derived stem cells (ADSCs) on cranial bone regeneration in rats, addressing the limitations of autogenous grafts and advancing bone tissue engineering with innovative photobiomodulation (PBM) applications. Methods: Sixty Wistar rats were allocated to 5 separate groups randomly; (1) natural bovine bone mineral (NBBM); (2) NBBM+LLLT; (3) NBBM+allogenic ADSCs; (4) NBBM+allogenic ADSCs+LLLT; (5) Only defects. 8-mm calvarial defects were made in each rat in the surgical procedure. A diode laser was applied with the following parameters (continuous mode, power of 100mW, wavelength of 808nm, and 4 J/cm2 energy density) immediately after the procedure and every other day. Bone samples were obtained and assessed histomorphometrically and histologically after staining with hematoxylin and eosin (H&E). Results: Different volumes of bony material were observed in two weeks; 2.94%±1.00 in group 1, 5.1%±1.92 in group 2, 7.11%±2.82 in group 3, 7.34%±2.31 in group 4, and 2.01%±0.83 in group 5 (P<0.05). On the other hand, foreign body residuals were up by 23% in the groups with scaffolding by the end of 2 weeks. Four weeks of observation led to 6.74 %±1.95, 13.24%±1.98, 15.76%±1.19, 15.92%±3.4, and 3.11%±1.00 bone formation in groups 1 to 5, respectively (P<0.05). Generally, the difference between groups 2-4 was not statistically significant based on different types of bone and the extent of inflammation. Conclusion: Bearing in mind the limitations of our research, it was demonstrated that ADSCs in combination with PBM have promising effects on bone tissue regeneration in sizeable bony defects. Furthermore, this study also showed that PBM usage improved the newly regenerated bone quality.

Controlled Lateral Pressure on Cortical Bone Using Blade-Equipped Implants: An Experimental Study in Rabbits.

BACKGROUND: This study aimed to evaluate the biological behavior of a novel implant design incorporating decompressive cervical blades. Hence, the aim of the present study was to evaluate the healing outcomes in cortical regions where decompressive protocols were implemented using implants equipped with blades and installed applying a bicortical anchorage. MATERIALS AND METHODS: Blades with varying diameters were integrated into the coronal portion of the implant to prepare the cortical region of rabbit tibiae. The blade diameters differed from the implant collar by the following amounts: control group (0 µm), +50 µm, and +200 µm. RESULTS: No marginal bone loss was detected. Instead, all implants exhibited new bone formation in the coronal region. Complete closure was observed in the CG-0 group, as well as in the TG-50 and TG-200 groups, despite the presence of marginal gaps without primary bone contact at installation. In the apical region, most implants breached the cortical layer. Nevertheless, new bone formation in this region completely closed the osteotomy, effectively isolating the internal environment of the tibia from the external. CONCLUSIONS: The use of a blade incorporated into the implant body enabled precise preparation of the cortical layer, allowing for controlled decompression in the targeted area. This technique resulted in optimal osseointegration with no loss of marginal bone, and complete restoration of marginal gaps ranging from 0 µm to 200 µm.

Short-Term Celecoxib Promotes Bone Formation without Compromising Cefazolin Efficacy in an Early Orthopaedic Device-Related Infection: Evidence from a Rat Model.

Non-steroidal anti-inflammatory drugs (NSAIDs) are crucial components of multimodal analgesia for musculoskeletal injuries, targeting cyclooxygenase (COX) enzymes (COX-1 and/or COX-2 isoenzymes). Concerns exist regarding their potential interference with bone healing and orthopaedic device-related infections (ODRI), where data are limited. This study aimed to investigate whether the COX-selectivity of NSAIDs interfered with antibiotic efficacy and bone changes in the setting of an ODRI. In vitro testing demonstrated that combining celecoxib (a COX-2 inhibitor) with cefazolin significantly enhanced antibacterial efficacy compared to cefazolin alone (p < 0.0001). In vivo experiments were performed using Staphylococcus epidermidis in the rat proximal tibia of an ODRI model. Long and short durations of celecoxib treatment in combination with antibiotics were compared to a control group receiving an antibiotic only. The long celecoxib treatment group showed impaired infection clearance, while the short celecoxib treatment showed increased bone formation (day 6, p < 0.0001), lower bone resorption (day 6, p < 0.0001), and lower osteolysis (day 6, BV/TV: p < 0.0001; BIC: p = 0.0005) compared to the control group, without impairing antibiotic efficacy (p > 0.9999). Given the use of NSAIDs as part of multimodal analgesia, and considering these findings, short-term use of COX-2 selective NSAIDs like celecoxib not only aids pain management but also promotes favorable bone changes during ODRI.

Comparative effect of skeletal stem cells versus bone marrow mesenchymal stem cells on rotator cuff tendon-bone healing.

Background: Bone marrow mesenchymal stem cells (BMSCs) have immense potential in applications for the enhancement of tendon-bone (T-B) healing. Recently, it has been well-reported that skeletal stem cells (SSCs) could induce bone and cartilage regeneration. Therefore, SSCs represent a promising choice for cell-based therapies to improve T-B healing. In this study, we aimed to compare the therapeutic potential of SSCs and BMSCs for tendon-bone healing. Methods: SSCs and BMSCs were isolated by flow cytometry, and their proliferation ability was measured by CCK-8 assay. The osteogenic, chondrogenic, and adipogenic gene expression in cells was detected by quantitative real-time polymerase chain reaction (qRT-PCR). C57BL/6 mice underwent unilateral supraspinatus tendon detachment and repair, and the mice were then randomly allocated to 4 groups: control group (tendon-bone interface without any treatment), hydrogel group (administration of blank hydrogel into the tendon-bone interface), hydrogel + BMSCs group (administration of hydrogel with BMSCs into the tendon-bone interface), and hydrogel + SSCs group (administration of hydrogel with SSCs into the tendon-bone interface). Histological staining, Micro-computed tomography (Micro-CT) scanning, biomechanical testing, and qRT-PCR were performed to assay T-B healing at 4 and 8 weeks after surgery. Results: SSCs showed more cell proportion, exhibited stronger multiplication capacity, and expressed higher osteogenic and chondrogenic markers and lower adipogenic markers than BMSCs. In vivo assay, the SSCs group showed a better-maturated interface which was characterized by richer chondrocytes and more proteoglycan deposition, as well as more newly formed bone at the healing site and increased mechanical properties when compared to other there groups. qRT-PCR analysis revealed that the healing interface in the SSCs group expressed more transcription factors essential for osteogenesis and chondrogenesis than the interfaces in the other groups. Conclusions: Overall, the results demonstrated the superior therapeutic potential of SSCs over BMSCs in tendon-bone healing. The translational potential of this article: This current study provides valuable insights that SSCs may be a more effective cell therapy for enhancing T-B healing compared to BMSCs.

Development and evaluation of an injectable ChitHCl-MgSO4-DDA hydrogel for bone regeneration: In vitro and in vivo studies on cell migration and osteogenesis enhancement.

Nonunion and delayed union of the bone are situations in orthopedic surgery that can occur even if the bone alignment is correct and there is sufficient mechanical stability. Surgeons usually apply artificial bone grafts in bone fracture gaps or in bone defect sites for osteogenesis to improve bone healing; however, these bone graft materials have no osteoinductive or osteogenic properties, and fit the morphology of the fracture gap with difficulty. In this study, we developed an injectable chitosan-based hydrogel with MgSO4 and dextran oxidative, with the purpose to improve bone healing through introducing an engineered chitosan-based hydrogel. The developed hydrogel can gelate and fit with any morphology or shape, has good biocompatibility, can enhance the cell-migration capacity, and can improve extracellular calcium deposition. Moreover, the amount of new bone formed by injecting the hydrogel in the bone tunnel was assessed by an in vivo test. We believe this injectable chitosan-based hydrogel has great potential for application in the orthopedic field to improve fracture gap healing.

Effectiveness of bone plate reduction combined with resorbable plate fixation in the treatment of large mandibular cysts.

OBJECTIVES: This study aims to observe the clinical effect of bone plate reduction in combination with a resorbable plate on large mandibular cysts. METHODS: Between October 2017 and September 2022, patients with large mandibular cysts in the presence of labial and buccal cortical bone were involved in the study. Intraoral approach was performed for bone plate reduction. Cone beam computed tomography (CBCT) scan was reviewed at 3, 6, and 9 months postoperatively to observe postoperative complications. Osteogenic results were assessed at these times to determine the clinical outcomes of this procedure. RESULTS: Eleven cases with large mandibular cysts in the presence of cortical bone were evaluated. The average thickness of the cortical bone on the labial and buccal sides was measured to be about (1.98±0.37) mm before surgery, with a mean value of (0.73±0.17) mm at the thinnest part of the plate and up to 0.51 mm at the thinnest part of the plate. The cystic cavities were well revealed during the surgeries, which were completed successfully. Postoperatively, the wounds healed in one stage without infection. The percentages of cyst shrinkage were 20.01%, 41.76%, and 73.41% at 3, 6, and 9 months after surgery, respectively. Quantitative measurement of bone mineral density in the jaws by CBCT with MIMICS software. The bone mineral densities of the adult bone were 313.78, 555.85, and 657.45 HU at the 3, 6, and 9 month time intervals, respectively. No significant change in the patient's maxillofacial appearance were observed from the preoperative period as assessed by the patient's and observer's visual analog scale. CONCLUSIONS: Bone plate reduction is an effective treatment for large mandibular cysts of the oral and maxillofacial region with the presence of cortical bone.