Bone Healing Research Articles

Multi-omics joint analysis reveals the mechanism underlying Chinese herbal Yougui Pill in the treatment of knee osteoarthritis

Ethnopharmacological relevanceYougui Pill (YGP), originating from Jingyue Quanshu, comprises 10 traditional Chinese medicines (TCMs). This classic prescription is renowned for its ability to tonify the kidney, warm the kidney, promote yang, warm the interior, and dispel cold. YGP has proven effective in treating degenerative knee arthritis, osteoporosis, delayed fracture healing, and other orthopedic conditions, making it a widely used clinical prescription for knee osteoarthritis (KOA).Aim of the study: Although YGP is commonly used in clinical practice, its pharmacodynamic material basis and anti-arthritis mechanisms remain unclear. This study aims to comprehensively analyze the chemical constituents of YGP and elucidate its anti-arthritis mechanisms. Materials and methodsUltra-high performance liquid chromatography coupled with electrospray ionization-triple quadrupole-linear ion trap mass spectrometry(ESI-Q TRAP-MS/MS) was used to identify the chemical constituents of YGP. The Hulth method was utilized to establish KOA rat model, and pathological examinations were performed to assess the anti-arthritis effects of YGP. Integrated metabolomics and transcriptomics analyses were conducted to explore the anti-arthritis mechanisms of YGP. Key targets were confirmed via immunohistochemistry. ResultsA total of 1981 chemical components were identified in YGP, predominantly phenolic acids and flavonoids. Compared with the model group, 422 differentially expressed metabolites and 214 differentially expressed genes were identified, primarily involving the MAPK signaling pathway, FoxO signaling pathway, and PI3K-Akt pathway. YGP exerted an anti-osteoarthritis effect by inhibiting the excessive activation of the EGFR/ERT/FOS signaling pathway. ConclusionsTCM offers significant advantages in the treatment of KOA, addressing the shortcomings of current clinical medications. YGP displayed exceptional pharmacodynamic effects. This study elucidated its pharmacodynamic material basis and anti-osteoarthritis mechanisms, providing substantial support for its clinical application and the development of related drugs.

Effectiveness of sacroiliac screw implantation assisted by three-dimensional printed faceted honeycomb guide plate in treatment of posterior pelvic ring fracture

To investigate the effectiveness of sacroiliac screw implantation assisted by three-dimensional (3D) printed faceted honeycomb guide plate in the treatment of posterior pelvic ring fracture. The clinical data of 40 patients with posterior pelvic ring fractures treated with sacroiliac screw implantation between December 2019 and December 2022 were retrospectively analyzed. Among them, 18 cases were treated with sacroiliac screws fixation assisted by 3D printed faceted honeycomb guide plate (guide plate group), and 22 cases were treated with sacroiliac screws percutaneously fixation under fluoroscopy (conventional group). There was no significant difference in baseline data ( P>0.05) such as gender, age, time from injury to operation, and Dennis classification between the two groups. The implantation time, frequency of C-arm X-ray fluoroscopy, frequency of guide pin adjustment of each sacroiliac screw, and postoperative complications and bone healing were recorded. Majeed score was used to evaluate the functional recovery at 6 months after operation, and CT was used to observe whether the screw penetrated the bone cortex. The deviation between the virtual position and the actual position of the screw tip, the sacral foramen, and the screw entry point was measured on the sagittal CT images of the guide plate group. The number of screws implanted in S 1 and S 2 vertebral bodies was 14 and 16 respectively in the guide plate group, and 17 and 18 respectively in the conventional group. The implantation time of each sacroiliac screw, the frequency of C-arm X-ray fluoroscopy, and the frequency of guide pin adjustment in S 1, S 2, and all vertebrae in the guide plate group were significantly less than those in the conventional group ( P<0.05). Patients in both groups were followed up 8-48 months, with an average of 19.7 months. There was no incision infection, screw displacement, or internal fixation loosening in both groups. Callus growth was observed in all patients at 12 weeks after operation, and bone healing was achieved in all patients. The healing time ranged from 12 to 24 weeks, with an average of 15.7 weeks. No sacroiliac screw penetrated the bone cortex in the guide plate group; 2 patients in the conventional group had sacroiliac screws penetrating the bone cortex without damaging blood vessels or nerves. In the guide plate group, the deviation between the virtual position and the actual position of the screw tip, the sacral foramen, and the screw entry point were (2.91±1.01), (2.10±0.74), and (1.67±0.70) mm, respectively, with an average deviation of (2.19±1.22) mm. There was no significant difference in Majeed function evaluation between the two groups at 6 months after operation ( P>0.05). The application of 3D printed faceted honeycomb guide plate in sacroiliac screw implantation for posterior pelvic ring fracture can shorten the screw implantation time, reduce the frequency of fluoroscopy and guide pin adjustment, and reduce the risk of screw penetration through the bone cortex.

Evaluation of Preoperative Factors That Affect the Alpha Angle of Screw Insertion After the Open Latarjet Procedure.

The open Latarjet procedure yields excellent results as a treatment for anterior shoulder instability. The position of the bony fragment and the insertion angle of the screw (the alpha angle) are critical factors for a successful procedure. The alpha angle is considered overangulated at >25°, which is associated with poor bone fixation and healing. To assess preoperative patient anatomic factors that affect the alpha angle in the Latarjet procedure for anterior shoulder instability. Case-control study; Level of evidence, 3. In this retrospective study, 76 patients who underwent the open Latarjet procedure between October 2009 and December 2023 were included. Postoperative computed tomography scans were reviewed for the alpha angle, and patients were classified into 2 groups: group 1 (alpha angle ≥25°) and group 2 (alpha angle <25°). Preoperative patient characteristics and radiological parameters obtained from preoperative computed tomography scans were analyzed and compared between groups 1 and 2. We developed a novel method to measure the depth of the chest and the angle between the deltopectoral interval and the plane of screw insertion. We also measured the thickness of the pectoralis major and subscapularis muscles. Of the 76 patients in this study, 41 and 35 patients were included in groups 1 and 2, respectively. The mean alpha angles of groups 1 and 2 were 36° and 12°, respectively, and the body mass index was significantly higher in group 1 (P < .001). In addition, group 1 had a significantly longer distance from the anterior edge of the glenoid to the skin margin of the deltopectoral interval (P < .001). The angle between the deltopectoral interval and the plane of screw insertion (traction angle) was significantly larger in group 1 (P < .001), and the pectoralis major and subscapularis muscles were thicker in group 1 (P = .017 and P = .032, respectively). The alpha angle after the Latarjet procedure was strongly related to the patient's weight, body mass index, depth of the chest, and the angle between the deltopectoral interval and the plane of screw insertion. To our knowledge, this is the first study in which the preoperative factors that facilitate proper screw fixation in the Latarjet procedure are reported.

Biomaterial Cues for Regulation of Osteoclast Differentiation and Function in Bone Regeneration

AbstractTissue regeneration involves dynamic dialogue between and among different cells and their surrounding matrices. Bone regeneration is specifically governed by reciprocity between osteoblasts and osteoclasts within the bone microenvironment. Osteoclast‐directed resorption and osteoblast‐directed formation of bone are essential to bone remodeling, and the crosstalk between these cells is vital to curating a sequence of events that culminate in the creation of bone tissue. Among bone biomaterial strategies, many have investigated the use of different material cues to direct the development and activity of osteoblasts. However, less attention has been given to exploring features that similarly target osteoclast formation and activity, with even fewer strategies demonstrating or integrating biomaterial‐directed modulation of osteoblast‐osteoclast coupling. This review aims to describe various biomaterial cues demonstrated to influence osteoclastogenesis and osteoclast function, emphasizing those that enhance a material construct's ability to achieve bone healing and regeneration. Additionally discussed are approaches that influence the communication between osteoclasts and osteoblasts, particularly in a manner that takes advantage of their coupling. Deepening the understanding of how biomaterial cues may dictate osteoclast differentiation, function, and influence on the microenvironment may enable the realization of bone‐replacement interventions with enhanced integrative and regenerative capacities.

Antibacterial bioadaptive scaffold promotes vascularized bone regeneration by synergistical action of intrinsic stimulation and immunomodulatory activity

The coupling of angiogenesis and osteogenesis is the fundamental necessity in bone fracture healing, thus simulative action of tissue-engineered bone provides powerful and beneficial effects in the treatment of bone defect. Herein, an immunoregulatory biocomposite scaffold with intrinsic activities of coupling angiogenesis and osteogenesis was constructed based on polyelectrolytes-modified 3D-printed scaffold for enhanced bone regeneration. The doping of Sr-doped hydroxyapatite (SrHA) within 3D-printed polycaprolactone (PCL) scaffold and subsequent slit guidance ligand 3 (SLIT3) protein adsorption through surface coating of carboxymethyl chitosan (CCS)/hyperbranched polylysine (HBPL) achieved on-demand delivery of SLIT3 and Sr ions. The antibacterial property of polyelectrolytes-modified scaffold was characterized and was directly proportional to the layer number of polyelectrolytes coating. The dual-factor delivery scaffold had good biocompatibility to support cell proliferation and migration, and was capable of stimulating angiogenesis and osteogenesis by intrinsic stimulation from released SLIT3 protein and Sr ions. Importantly, the multifunctional scaffold had immunomodulatory effects of promoting M2-type polarization of macrophages and thereby increasing anti-inflammatory factors level, as well as indirectly promoting angiogenesis and osteogenesis. The in vivo experiments revealed that the anti-inflammatory effect was significantly reinforced for providing a better regenerative microenvironment and bone regeneration capacity was dramatically enhanced accompanied with type H vessels formation when implanted with multifunctional scaffold. Therefore, the bioadaptive scaffold possessed amplified bone regeneration performance through intrinsic stimulation and immunomodulatory effects, suggesting a promising therapeutic candidate for bone defect repair.

LncRNA CASC11 regulates the progress of delayed fracture healing via sponging miR-150-3p

BackgroundLong non-coding RNA (lncRNA) plays a pivotal role in bone regeneration by interaction with microRNAs (miRNAs) and constructing a lncRNA-miRNA regulatory network.ObjectivesThis research aimed to elucidate the role of lncRNA CASC11 in the delayed healing process of tibial fractures and to explore its potential regulatory mechanisms.Materials and methodsThe expression levels of CASC11 and miR-150-3p in serum samples were detected and the predictive capability of CASC11 regarding delayed healing in fracture patients. Furthermore, the study confirmed the accuracy of the binding sites between CASC11 and miR-150-3p. Subsequently, overexpression/interference plasmids of CASC11, along with overexpression plasmids co-transfected with both CASC11 and miR-150-3p, were systematically introduced into MC3T3-E1 cells to investigate their effects on the expression of osteogenic marker genes, as well as their influence on cellular proliferation and apoptosis.ResultsThe expression levels of CASC11 were significantly elevated, while miR-150-3p levels were markedly decreased in individuals exhibiting delayed fracture healing (P < 0.001). CASC11 was observed to suppress the expression of osteogenic marker genes, inhibit the proliferation of MC3T3-E1 cells, and promote cell apoptosis (P < 0.05). Furthermore, the overexpression of miR-150-3p effectively countered the inhibitory impact of CASC11 on osteogenic differentiation and the promoting effect on cell apoptosis (P < 0.05).ConclusionThe sponging effect of CASC11 on miR-150-3p led to delayed fracture healing. CASC11 emerges as a potential target for treating delayed fracture healing.

Optimizing α-tricalcium phosphate bone cement composite formulations: The critical role of bioactive glass particle size

Calcium phosphate cements (CPCs) have been extensively utilized as bone grafting material due to their inherent osteoconductive properties, although they often lacked sufficient biological performance for effective bone healing at the defect site. Incorporating mesoporous bioactive glass (MBG) into CPCs offers a solution by improving porosity, promoting degradation and increasing the available surface area. In the scope of this study, we integrated MBG into CPCs and assessed the impact of varying MBG particle sizes (<20 µm, <38 µm, <100 µm) on the setting characteristics, microstructure, mechanical strength, and preliminary cell response of CPCs. Investigations revealed that < 20 µm MBG particles significantly improved the setting characteristics and compressive strength of CPCs, while < 38 µm particles promoted degradation and ion release, facilitating apatite formation. MBG incorporation was found to promote microstructural homogeneity and facilitate apatite formation, with particle size directly affecting these outcomes. Biocompatibility assessments indicated no cytotoxic effects, supported by the favorable cellular responses (> 92 % viability compared to control group). These findings underscore the critical impact of MBG particle size on developing advanced CPCs for biomedical applications, guiding future design and optimization strategies.

Framework Nucleic Acid-Based Selective Cell Catcher for Endogenous Stem Cell Recruitment.

Cell-surface engineering holds great promise in boosting endogenous stem cell attraction for tissue regeneration. However, challenges such as cellular internalization of ligand and the dynamic nature of cell membranes often complicate ligand-receptor interactions. The aim of this study is to harness the innovative potential of programmable tetrahedral framework nucleic acid (tFNA) to enable precise, tunable ligand-receptor interactions, thereby improving stem cell recruitment efficiency. This approach involves experimental screening and theoretical analysis using dissipative particle dynamics. The results demonstrate that altering the flexibility and topology of ligands on tFNA changes their cellular internalization and membrane binding efficiency. Furthermore, optimizing the distribution of the mesenchymal stem cell (MSC)-binding aptamer 19S (Apt19S) on the tFNA enhances the stem cell capture efficiency. Following successful in vitro MSC capture, Apt19S-modified tFNA is chemically linked to a hyaluronic acid hydrogel, forming an efficient "stem cell catcher" system. Subsequent in vivo experiments demonstrate that this system effectively promotes early stem cell recruitment and accelerates bone regeneration in different bone healing scenarios, including cranial and maxillary defects.

Bilateral neck of femur stress fracture secondary to osteopetrosis treated with dynamic hip screw

Osteopetrosis, a rare hereditary bone disorder, is characterized by increased bone density due to defective osteoclast-mediated bone resorption. This condition often leads to skeletal fragility, resulting in recurrent fractures despite increased bone mass. Among these, stress fractures of the femoral neck pose a unique challenge where conventional management may not be optimal. Valgus osteotomy offers a viable surgical intervention to realign the mechanical axis, thereby reducing stress on the femoral neck and facilitating healing. This paper reviews the pathophysiology of osteopetrosis, its impact on fracture healing, and the role of valgus osteotomy in managing femoral neck stress fractures in osteopetrotic patients.

Local Delivery of Melatonin Along With Bone Grafts to Improve Osteogenesis

This review is an attempt to investigate the effects of local delivery of melatonin along with bone grafts to improve osteogenesis. A systematic literature search was done from January 1970 to December 2023 using PubMed following PRISMA instructions. A structured search was carried out to identify in vivo and in vitro studies. After screening the articles based on the abstract and title, 24 articles were included. The included studies were animal/human in vivo studies or in vitro studies. In total, 91.7% of the studies reported better outcomes in comparison with the control groups. Melatonin potentially can affect many signaling molecules and pathways promoting osteoblastic differentiation, such as activating pathways including Wnt, Nrf2/HO-1, PI3K/AKT, MAPK, NFkB, SIRT/SOD, BMP/Smad, PERK/ATF4. In conclusion, locally administered melatonin may stimulate bone healing in surgical bone defects and enhance peri-implant bone response.

Integrating 3D-printed customized guides with hemicorticotomy bone transport: clinical outcomes in chronic osteomyelitis management

PurposeChronic osteomyelitis with large bone defects remains a challenging condition in orthopedic surgery. This study aimed to evaluate the clinical efficacy of hemicorticotomy bone transport assisted by 3D-printed customized guides in the treatment of chronic osteomyelitis with bone defects.MethodsA retrospective analysis was conducted on 21 patients with chronic osteomyelitis treated with hemicorticotomy bone transport with 3D-printed guide assistance between January 2015 and January 2021. Preoperative planning utilized 3D CT reconstruction for precise guide design and osteotomy placement. The surgical technique involved hemicorticotomy, placement of the 3D-printed guide, and gradual bone transport using a monolateral external fixator. Clinical outcomes were assessed using the Association for the Study and Application of Methods of Ilizarov (ASAMI) scoring system. The external fixation time (EFT), external fixation index (EFI), and complications evaluated using the Paley classification were recorded.ResultsThe mean bone defect size was 7.9 ± 2.0 cm. The average follow-up period was 28.6 ± 6.4 months. The mean external fixation time was 289.4 ± 52.7 days, with an external fixation index of 36.8 ± 4.2 days/cm. According to the ASAMI criteria, the bone results were excellent in 17 patients (81%), good in 3 (14%), and fair in 1 (5%). The functional results were excellent in 15 patients (71%), good in 4 (19%), and fair in 2 (10%). Complete eradication of the infection and union at the docking site were achieved in all patients. The complication rate was 38% and all of which were successfully managed.ConclusionHemicorticotomy bone transport assisted by 3D-printed customized guides is an effective treatment for chronic osteomyelitis with bone defects. This technique offers excellent bone healing, favorable functional results, and a relatively low complication rate. Further studies with larger sample sizes are warranted to validate these findings.

The Effect of Platelet-Rich Fibrin (PRF) in Accelerating Periodontal Regeneration: A Randomized Controlled Clinical Trial

ABSTRACT Background: Regeneration of periodontal tissues is an essential component in treating periodontal disease, and there is an increasing focus on biological agents that might improve the healing process. Materials and Methods: The randomized controlled clinical study included a cohort of 60 individuals diagnosed with chronic periodontitis. Each participant was randomly allocated to one of two groups: the experimental group (n = 30), which underwent PRF in combination with traditional open flap debridement (OFD), and the control group (n = 30), which received OFD alone. Clinical criteria such as probing pocket depth (PPD), clinical attachment level (CAL), and bone fill percentage were assessed at baseline and after 6 months. Furthermore, cone-beam computed tomography (CBCT) was used to evaluate bone regrowth radiographically. Results: Following a period of 6 months, the experimental group had a notable decrease in postpartum depression (mean decrease of 4.2 mm) and an increase in central artery ligation (mean increase of 3.5 mm) compared to the control group, which had a mean decrease in postpartum depression of 2.8 mm and a mean increase in central artery ligation of 2.1 mm. The test group had a notably greater proportion of bone fill (45%) in comparison to the control group (30%). Further radiographic study verified enhanced bone regeneration in the areas treated with PRF. Conclusion: The use of Platelet-Rich Fibrin (PRF) in combination with traditional periodontal surgery greatly expedites the process of periodontal regeneration, as shown by notable enhancements in clinical indicators and bone regeneration.

Evaluation of the Tobacco Heating System (THS) During Closed Lower Limb Fracture Healing in Trauma Smokers’ Patients

BACKGROUND: Since 1976, it's been recognized that increased cigarette consumption correlates with decreased bone density, hindering fracture healing and leading to prolonged hospitalization. Although prior research has shown the relatively less harmful effects of electronic nicotine delivery systems (ENDS) on bone cells in lab settings and animal models, clinical evidence regarding their impact on fracture healing remains scarce. This study aims to investigate whether switching to a tobacco heating system (THS) post-orthopedic surgery improves outcomes for smoking patients during tibia or femur fracture healing over a 6-month period. METHODS: The study is a prospective, open-label, non-parallel, single-center trial involving 150 patients from a Level 1 Trauma center, Germany, diagnosed and treated for closed tibia, closed femur shaft, or closed distal femur fractures (according to AO/OTA: 41A2-41C3, 42A-C, 43A-C, 32A-C, 33A2-3, 33B-C). Participants will be categorized into three groups based on smoking behavior: smokers (no intervention), THS (participants switching from cigarettes to THS), and ex-smokers (participants abstaining from cigarettes or ENDS during the study). Clinical, radiological, and laboratory data will be collected during preoperative and postoperative assessments at 6, 12, 18, and 24 weeks. The primary outcome will be the serum concentration of N-terminal propeptide procollagen type 1, a bone formation marker. Secondary outcomes include bone metabolism, healing, immunological, blood count, and clinical parameters. Approval for the study protocol and consent declarations was obtained from the ethics committee of the medical faculty of Eberhard Karls University (724/2022BO1). DISCUSSION: The study results will provide evidence that switching to THS previous orthopedic intervention improves clinical outcomes during closed tibia or femur fracture healing in smokers’ patients due to reduced bone resorption rate consequent to the diminished activity of cigarette smoke-activated osteoclast.

Propolis in Dental Implantology: A Systematic Review of Its Effects and Benefits.

Dental implants are widely recognized for their effectiveness in restoring missing teeth, yet their success is often compromised by infections or inadequate osseointegration. Propolis, a natural resinous substance with potent antimicrobial, anti-inflammatory, and osteogenic properties, has emerged as a promising adjunct in dental implantology. This systematic review critically evaluates the current evidence on the incorporation of propolis into dental implants, focusing on its impact on antimicrobial efficacy, bone healing, and overall implant stability. The study protocol was registered in PROSPERO under the registration number CRD42024577122. The PRISMA diagram visually represented the search strategy, screening, and inclusion process. Two reviewers conducted a comprehensive literature search across five databases: PubMed, PubMed Central, Embase, Scopus, and Web of Science. The review synthesized findings from 13 studies; in vitro, in vivo, and clinical studies, highlighting that propolis significantly enhances antibacterial and antifungal activities against pathogens such as Staphylococcus aureus, Candida albicans, and Streptococcus mutans, thereby reducing the risk of peri-implant infections. Additionally, propolis promotes osseointegration by stimulating osteoblast activity and reducing inflammatory cytokine expression, leading to improved bone formation and implant stability. The anti-inflammatory and antioxidant properties of propolis further contribute to a favorable healing environment, enhancing the long-term success of dental implants. The systematic review underscores the potential of propolis as a safe, biocompatible, and effective material for improving dental implant outcomes. However, it also identifies the need for more extensive clinical trials to fully establish standardized protocols for propolis application in implantology. This review provides an overview of propolis's potential role in dental implants and suggests promising avenues for future research to optimize its benefits in clinical practice.

Modified double-row suture bridge technique for anterior colliculus fractures combined with deltoid ligament injury: a retrospective study

BackgroundThe management of anterior colliculus fractures in combination with deltoid ligament injuries is a topic of debate, and there is a need to improve surgical outcomes. The purpose of the present study was to describe the application of a modified double-row suture bridge technique and evaluate its early clinical outcomes in the management of anterior colliculus fracture combined with deltoid ligament injury.MethodsFrom 2020 to 2022, 12 patients with anterior colliculus fracture combined with deltoid ligament injury were treated using a modified double-row suture bridge technique. For clinical outcome evaluation, objective data are presented through clinical examination findings; radiographic assessments, including X-rays and computed tomography (CT); and follow-up analysis utilizing American Orthopaedic Foot & Ankle Society ankle‒hindfoot (AOFAS) scores, Olerud Molander Ankle Scores (OMAS), and visual analogue scale (VAS) scores. Preoperative and follow-up scores were compared with Student’s t test. (p < .05).ResultsThe mean age of the patients was 52.67 ± 9.42 years (range: 39–74). The mean duration of follow-up was 14.42 ± 1.51 months (range: 12–17). At the final follow-up, the mean AOFAS score (P < 0.001) improved to 91.50 ± 2.65 points (range: 87–96), the mean OMAS (P < 0.001) improved to 77.08 ± 3.97 points (range: 70–85), and the mean VAS score (P < 0.001) improved to 0.25 ± 0.45 points (range: 0–1). Nine patients achieved excellent outcomes, and three achieved good outcomes according to the AOFAS score. Follow-up imaging evaluation indicated satisfactory alignment of the fracture and complete healing. Clinical examination suggested good mobility of the ankle. At the last follow-up, ankle dorsiflexion mobility was 14–18 degrees, plantar flexion mobility was 42–45 degrees, inversion mobility was 27–32 degrees, and eversion mobility was 22–25 degrees.ConclusionsThe modified double-row suture bridge technique is effective for achieving anatomic reduction of anterior colliculus fractures, and the technique also provides substantial benefit to the injured deltoid ligament. With this technique, the clinical outcomes can be significant and encouraging, indicating a new stage in its application and development.

PREVENÇÃO E TRATAMENTO DA COMUNICAÇÃO BUCO-SINUSAL EM PROCEDIMENTOS ODONTOLÓGICOS: REVISÃO DE TÉCNICAS CIRÚRGICAS E BIOMATERIAIS

Oroantral communication (OAC) is a frequent complication in dental procedures, especially in extractions of upper posterior teeth due to the anatomical proximity to the maxillary sinus. This review addresses the main surgical techniques and the use of biomaterials in the treatment of OAC, based on articles published between 2010 and 2024, found in databases such as PubMed and Scielo. Risk factors like the proximity of dental roots to the floor of the maxillary sinus and advanced age increase the likelihood of OAC, with cone-beam computed tomography (CBCT) being an effective tool in preoperative evaluation. Minimally invasive surgical techniques, such as controlled osteotomy and piezosurgery, have been effective in preventing perforations, while biomaterials like collagen membranes and bone grafts are widely used in treating larger perforations, promoting bone regeneration and healing. The combination of appropriate sutures and biomaterials is essential to avoid postoperative complications such as chronic sinusitis and fistulas. The review concludes that despite advances in surgical techniques and the use of biomaterials, gaps remain in the literature regarding the management of complex perforations, highlighting the need for more comparative studies to optimize OAC treatment. An integrated approach—including preoperative evaluation, appropriate surgical techniques, and postoperative follow-up—is crucial for treatment success and the reduction of long-term complications.

Histopathological and radiological evaluation of the efficacy of hydroxyapatite–boric acid and hydroxyapatite–magnesium coated Kirschner wires on fracture healing in femoral diaphyseal fractures: an experimental study

BackgroundBiomaterials used in fracture healing hold a significant place in orthopedics. This study aimed to develop biomaterials coated with hydroxyapatite (HA), boric acid (BA), and magnesium (Mg) and investigate their effects on fracture healing.MethodsSixty female Wistar Albino rats were included in the study. The subjects were randomized into five groups. Cytotoxicity tests were performed on HA, BA, and Mg, and cell viability rates were calculated. Coatings were applied to Kirschner (K) wires at determined ratios. Group I was the control group with a steel K wire, Group II used HA-coated K wires, Group III used HA + BA-coated K wires, Group IV used HA + BA + Mg-coated K wires, and Group V used HA + Mg-coated K wires. A fracture was induced in the right femur of the subjects, followed by fixation with intramedullary K wires. The subjects were randomly divided into equal numbers and sacrificed at 6 and 12 weeks. Radiological and histopathological evaluations were performed.ResultsIn direct cytotoxicity tests, the highest viability rate was observed in Group IV, while in indirect cytotoxicity tests, it was highest in Group II. In radiological evaluation at the 6th week, the highest scores were in Groups IV and V, while the lowest was in Group III. At the 12th week, the highest scores were in Groups II and V, while the lowest was in Group I. No significant differences were found between the groups (p = 0.837, p = 0.0479). In histopathological evaluation, a significant difference was observed between the groups (p < 0.001), with the highest scores in Group V. A correlation was found between the radiological and histopathological scores (p < 0.001, r = 0.438).ConclusionIt was found that HA + Mg significantly improved histological outcomes in fracture healing. Good histological results can be achieved with the use of Mg-containing implants in both early and late-stage fracture healing. Coating the biomaterials used in fracture fixation with Mg may lead to positive outcomes in fracture healing.

Effect of nHA/CS/PLGA delivering adipose stem cell-derived exosomes and bone marrow stem cells on bone healing—in vitro and in vivo studies

Adipose stem cell-derived exosomes (ADSC-EXO) have been demonstrated to promote osteogenic differentiation of bone marrow stem cells (BMSCs) and facilitate bone regeneration. The present study aims to investigate the effect of ADSC-EXO-loaded nano-hydroxyapatite/chitosan/poly-lactide-co-glycolide (nHA/CS/PLGA) scaffolds on maxillofacial bone regeneration using tissue engineering. ADSC-EXO was isolated and co-cultured with BMSCs, and the osteogenic differentiation of BMSCs was assessed through the detection of mineralized nodule formation, alkaline phosphatase (ALP) activity, and mRNA expression of COL1A1 and runt-related transcription factor 2 (RUNX2). The nHA/CS/PLGA scaffolds were fabricated and loaded with ADSC-EXO and BMSCs, and these tissue engineering complexes were applied to the maxillofacial bone defect region of rabbits to elucidate their bone regeneration effect. The osteogenic differentiation of BMSCs was markedly enhanced when they were co-cultured with ADSC-EXO. This was evidenced by an increase in the formation of mineralized nodule formation, ALP activity, and mRNA expression of COL1A1 and runt-related transcription factor 2 (RUNX2). In vivo experiments demonstrated that the application of ADSC-EXO and BMSCs loaded nHA/CS/PLGA scaffolds effectively repaired maxillofacial bone defects in rabbits. ADSC-EXO has been demonstrated to promote the osteogenic differentiation of BMSCs. The ADSC-EXO and BMSCs loaded nHA/CS/PLGA scaffolds have been shown to facilitate the regeneration of maxillofacial bone defects. This may serve as a potential therapeutic strategy for large-scale bone defects.

Treatment of Bone Defects and Nonunion via Novel Delivery Mechanisms, Growth Factors, and Stem Cells: A Review.

Bone nonunion following a fracture represents a significant global healthcare challenge, with an overall incidence ranging between 2 and 10% of all fractures. The management of nonunion is not only financially prohibitive but often necessitates invasive surgical interventions. This comprehensive manuscript aims to provide an extensive review of the published literature involving growth factors, stem cells, and novel delivery mechanisms for the treatment of fracture nonunion. Key growth factors involved in bone healing have been extensively studied, including bone morphogenic protein (BMP), vascular endothelial growth factor (VEGF), and platelet-derived growth factor. This review includes both preclinical and clinical studies that evaluated the role of growth factors in acute and chronic nonunion. Overall, these studies revealed promising bridging and fracture union rates but also elucidated complications such as heterotopic ossification and inferior mechanical properties associated with chronic nonunion. Stem cells, particularly mesenchymal stem cells (MSCs), are an extensively studied topic in the treatment of nonunion. A literature search identified articles that demonstrated improved healing responses, osteogenic capacity, and vascularization of fractures due to the presence of MSCs. Furthermore, this review addresses novel mechanisms and materials being researched to deliver these growth factors and stem cells to nonunion sites, including natural/synthetic polymers and bioceramics. The specific mechanisms explored in this review include BMP-induced osteoblast differentiation, VEGF-mediated angiogenesis, and the role of MSCs in multilineage differentiation and paracrine signaling. While these therapeutic modalities exhibit substantial preclinical promise in treating fracture nonunion, there remains a need for further research, particularly in chronic nonunion and large animal models. This paper seeks to identify such translational hurdles which must be addressed in order to progress the aforementioned treatments from the lab to the clinical setting.

GelMA hydrogels reinforced by PCL@GelMA nanofibers and bioactive glass induce bone regeneration in critical size cranial defects

BackgroundThe process of bone healing is complex and involves the participation of osteogenic stem cells, extracellular matrix, and angiogenesis. The advancement of bone regeneration materials provides a promising opportunity to tackle bone defects. This study introduces a composite hydrogel that can be injected and cured using UV light.ResultsHydrogels comprise bioactive glass (BG) and PCL@GelMA coaxial nanofibers. The addition of BG and PCL@GelMA coaxial nanofibers improves the hydrogel’s mechanical capabilities (353.22 ± 36.13 kPa) and stability while decreasing its swelling (258.78 ± 17.56%) and hydration (72.07 ± 1.44%) characteristics. This hydrogel composite demonstrates exceptional biocompatibility and angiogenesis, enhances osteogenic development in bone marrow mesenchymal stem cells (BMSCs), and dramatically increases the expression of critical osteogenic markers such as ALP, RUNX2, and OPN. The composite hydrogel significantly improves bone regeneration (25.08 ± 1.08%) in non-healing calvaria defects and promotes the increased expression of both osteogenic marker (OPN) and angiogenic marker (CD31) in vivo. The expression of OPN and CD31 in the composite hydrogel was up to 5 and 1.87 times higher than that of the control group at 12 weeks.ConclusionWe successfully prepared a novel injectable composite hydrogel, and the design of the composite hydrogels shows significant potential for enhancing biocompatibility, angiogenesis, and improving osteogenic and angiogenic marker expression, and has a beneficial effect on producing an optimal microenvironment that promotes bone repair.