Bone Healing In Rats Research Articles

Piezocatalytic strategy facilitates diabetic bone regeneration through high-performance anti-oxidative recycling

Anti-oxidative therapy for resistance of oxidative stress-induced damage has attracted substantial attention for bone regeneration under diabetic conditions. However, most anti-oxidants suffer from low efficiency due to their one-off reaction with oxidative products and rapid loss of activity. Herein, the piezoelectric nanocomposite with built-in electric field was fabricated as a cyclic anti-oxidative device for improved reactive oxygen species (ROS) scavenging and pro-osteogenic outcome. Under ultrasound (US) irradiation, the polydopamine (PDA) -functionalized generator with piezocatalytic effect exhibits high-performance recycling of redox catalytic reaction via continuous electron supplementation for cyclic group switch from quinone to phenol. The piezocatalytic method substantially boosts ROS elimination and reverses inflammatory status, contributing to strengthened osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and M2 polarization of macrophages. In vivo results further validated superior bone healing in rats with diabetes mellitus (DM). Our study therefore provides fundamental insights into the potential value of piezocatalytic effect-triggered cyclic anti-oxidative function for optimized osteogenesis under DM condition, and lays a basis for application of piezocatalytic effect in regenerative medicine.

Dose-response association of smoking with delayed healing of apical periodontitis after endodontic treatment.

A prospective cohort study aimed to assess the inhibitory effect of cigarette smoking on the rate of periapical bone healing after root canal treatment (RCT). Examination included both clinical and radiographic parameters to define healing status at baseline, 6 months, and 1 year after RCT. To examine and compare the healing rate of apical periodontitis (AP) after RCT between smokers and nonsmokers, and to evaluate how the intensity and duration of smoking affect AP healing up to 1-year follow-up. Study hypothesis was that smoking habits could delay or deteriorate AP healing. The study protocol was approved by the local ethics committee and all of the participants signed a consent form. Included were adult patients with a radiographically confirmed AP in a single tooth with a favorable periodontal prognosis and adequate coronal restoration, with no previous RCT. Excluded patients were those diagnosed with a systemic disease or on medications affecting bone metabolism, former and occasional smokers, pregnant patients, and those who refused to participate. Smokers were defined as those who consumed at least 100 cigarettes in their lifetime and currently smoke. Smoking intensity was classified according to cigarette consumption per day (CPD) into: heavy smoking (≥20 CPD) and mild smoking (˂20 CPD). Tobacco exposure over time was assessed by smoking index (=CPD ˟ duration of tobacco smoking in years) and categorized into: nonsmoker, <400, 400-799, and ≥800. The control group included healthy nonsmokers and matched the smoker group in termsof age and gender. All RCTs were performed by endodontic specialists following a standardized protocol. Clinical examination involved percussion and palpation tests, periodontal probing and examination of the coronal restoration; while the periapical healing was radiographically assessed using the periapical index (PAI) scoring. A total of 110 patients (55 smokers and 55 nonsmokers) were included. The two groups were comparable regarding age, gender, tooth type, socioeconomics, and periapical index scores at the baseline. The mean CPD among smokers was 12.22, and most of them were "mild smokers". At 12-month follow-up, nonsmokers showed a significantly higher healing rate compared to smokers (90.9% vs. 58.2%; χ2 = 13.846; p < 0.001). Conversely, smokers had significantly higher PAI when compared to the control group (p = 0.024). Regression analysis demonstrated that the risk of AP persistence increases with an increase in the smoking index [OR = 7.66; 95% CI: 2.51-23.28; p < 0.001, for smoking index <400 and (OR = 9.65; 95% CI: 1.45-64.14; p = 0.019, for smoking index 400-799]. Smoking was significantly associated with delayed AP healing after RCT. The likelihood of AP persistence rises as smoking exposure increases. These results could impact clinical decisions and guidelines concerning smokers.

Induced membrane technique versus one-stage autografting in management of atrophic nonunion of long bone in the lower limb: clinical and health burden outcomes

ObjectiveIn this study, we aimed to compare the outcomes of the two-stage induced membrane technique (IMT) and one-stage autografting in the treatment of aseptic atrophic nonunion in lower limb long bones.MethodsFrom January 2014 to January 2022, we reviewed all surgically treated long bone nonunion patients, including patients aged 18 years or older with atrophic nonunion, who were either treated with the two-stage induced membrane technique (IMT) or one-stage autografting. Outcome parameters interns of clinical, quality of life and healthcare burden were recorded and retrospectively analysed between the two treatment populations. The follow-up time was at least 1 year.ResultsIn total, 103 patients who met the criteria for aseptic atrophic nonunion were enrolled. Among them, 41 (39.8%) patients were treated with two-stage IMT, and 62 (60.2%) patients were treated with one-stage autologous bone grafting. The follow-up time was 12 to 68 months, with an average of 28.4 months. The bone healing rate was comparable in both groups (IMT: 92.7% vs. one-stage grafting: 91.9%, P = 0.089) at 12 months post-operation, and the bone healing Lane–Sandhu score was superior in the IMT group (mean: 8.68 vs. 7.81, P = 0.002). Meanwhile, the SF-12 scores of subjective physical component score (PCS) (mean: 21.36 vs. 49.64, P < 0.01) and mental health component score (MCS) (mean: 24.85 vs. 46.14, P < 0.01) significantly increased in the IMT group, as well as in the one-stage grafting group, and no statistically significant difference was found within groups. However, the total hospital stays (median: 8 days vs. 14 days, P < 0.01) and direct medical healthcare costs (median: ¥30,432 vs. ¥56,327, P < 0.05) were greater in the IMT group, while the complications (nonunion 8, infection 3, material failure 2, and donor site pain 6) were not significantly different between the two groups (17.1% vs. 19.4, P = 0.770).ConclusionThe data indicate that two-stage method of IMT serves as an alternative method in treating atrophic nonunion; however, it may not be a preferred option, in comprehensive considering patient clinical outcomes and healthcare burden. More evidence-based research is needed to further guide clinical decision-making.

Multifunctional DNA-Based Hydrogel Promotes Diabetic Alveolar Bone Defect Reconstruction.

Diabetic alveolar bone defect (DABD) causes persistent bacterial infection, prolonged inflammation, and delayed bone healing, making it a considerable clinical challenge. In this study, by integrating silver nanoclusters (AgNCs) and M2 macrophage-derived extracellular vesicles (M2EVs), a multifunctional DNA-based hydrogel, called Agevgel, is developed with antibacterial, anti-inflammatory, immunomodulatory, and osteogenic properties to promote DABD rebuilding. AgNCs are tightly embedded into the DNA scaffolds and exhibit effective anti-bacterial activity, while immunomodulatory M2EVs are encapsulated within the shape-variable DNA scaffolds and exhibit potent anti-inflammatory and osteogenic properties. The results reveal that Agevgel effectively prolongs the local retention time and bioactivity of M2EVs in vivo. In particular, the sustained release of M2EVs can last for at least 7 days when applying Agevgel to DABD. Compared to free M2EVs or Aggel (AgNCs encapsulated within the DNA hydrogel) treatments, the Agevgel treatment accelerates the defect healing rate of alveolar bone and dramatically improves the trabecular architecture. Mechanistically, Agevgel plays a key role in regulating macrophage polarization and promoting the expression of proliferative and osteogenic factors. In summary, Agevgel provides a comprehensive treatment strategy for DABD with a great clinical translational value, highlighting the application of DNA hydrogels as an ideal bioscaffolds for periodontal diseases.

Inlay structure can improve bone graft stability in the Bristow procedure

Compared with the Latarjet procedure, the Bristow procedure has a lower screw-related complication rate but poor bone healing. A modified Inlay Bristow procedure has been reported to significantly improve the bone healing rate, but the biomechanical mechanism is unclear. The aim of this study was to evaluate the biomechanical stability of the bone graft between a modified Inlay Bristow procedure and the classic Bristow procedure. Sixteen left scapula models (Sawbones, Composite Scapula, 4th generation) were randomly divided into two groups (8:8). The bone graft in the first group was fixed with a 3.5 mm screw using the Inlay structure. The bone graft in the second group was fixed with a 3.5 mm screw via the traditional method. The maximum cyclic displacement, ultimate failure load and stiffness were evaluated biomechanically. The failure type was recorded for each model. Cyclic loading tests demonstrated that the maximum cyclic displacement of the Inlay procedure was significantly smaller (P = 0.001) than that of the classic procedure. The Inlay Bristow technique resulted in a significantly higher (P = 0.024) ultimate failure load than the classic Bristow technique. The stiffness of the classic group was 19.17±4.01 N/mm and that of the inlay group was 22.34±5.35 N/mm (P = 0.232). Failure was mainly due to bone graft fractures through the drill hole or glenoid bone fractures. Inlay Bristow fixation of the bone graft in a Sawbones model provides significantly stronger fixation and better time point zero stability than classic Bristow fixation, suggesting a higher likelihood of graft union.

Comparison of two different intramedullary rods combined with Ilizarov external fixation and wrapped autologous iliac bone grafting for the treatment of congenital tibial pseudarthrosis in children

Objective: To compare the initial clinical efficacy of extensible intramedullary rod fixation and Williams intramedullary rod fixation combined with Ilizarov external fixation and wrapped autologous iliac bone grafting in the treatment of congenital tibial pseudarthrosis in children. Methods: A retrospective analysis was conducted on the clinical data of 60 children with Crawford Ⅳtype congenital pseudarthrosis of the tibia treated with combined surgery at the Orthopedics Department of Hunan Children's Hospital from January 2013 to December 2020.According to different internal fixation methods,patients were divided into the extensible intramedullary rod group (30 cases) and the Williams intramedullary rod group (30 cases). There were 12 males and 18 females in the extendable intramedullary rod group, aged (33.6±6.3) months (range: 18 to 44 months), while there were 10 males and 20 females in the Williams intramedullary rod group, aged (47.8±8.6) months (range: 36 to 66 months). The anteroposterior and lateral views of tibia and fibula and the full length anteroposterior film of both lower limbs were examined to compare the clinical treatment effects of the two groups at 1-,3-,6-,9-, and 12-month after surgery. Independent sample t-test, χ2 test or Fisher exact test was used for inter group comparison. Results: Both groups of children underwent surgery successfully, with postoperative follow-up time greater than 2 years. The extensible intramedullary rod group was followed up for (49.5±6.4) months, while the Williams intramedullary rod group was followed up for (53.7±10.5) months. The initial bone healing time between the broken ends of the tibial pseudarthrosis was (5.1±0.8) months in the extensible intramedullary rod group and (5.0±0.6) months in the Williams intramedullary rod group. There was no statistically significant difference between the two groups (t=0.584, P=0.562). The initial postoperative bone healing rate of the extensible intramedullary rod group was 93.3% (28/30), while that of the Williams intramedullary rod group was 96.7% (29/30). There was no statistically significant difference between the groups (χ2=0.351 P=0.554).The postoperative fracture rate of the extensible intramedullary rod group was 20.0% (6/30), while that of the Williams intramedullary rod group was 16.7% (5/30);Six cases (20.0%) in the extensible intramedullary rod group had unequal limb lengths in both lower limbs after surgery, with a limb length difference of (2.5±1.4)cm (range: 1.5 to 5.2 cm). Eight cases (26.7%) in the Williams intramedullary rod group had a limb length difference of (2.8±1.4)cm (range: 1.8 to 6.0 cm);After surgery, there were 4 (13.3%) cases of proximal tibial valgus deformity in the extensible intramedullary rod group, with an valgus angle range of (12.5±4.9)° (range: 7 °to 18°), and 3 (10.0%) cases in the Williams intramedullary rod group, with an valgus angle of (15.0±6.0)° (range: 9°to 21°). There were 2 (6.7%) cases of ankle valgus deformity in the extensible intramedullary rod group, with an valgus angle of (11.5±4.9)° (range: 8 °to 15°), and 4 (13.3%) cases in the Williams intramedullary rod group, with an valgus angle of (14.8±6.2)° (range: 6 °to 20°). The postoperative activities of the knee and ankle joints in the extensible intramedullary rod group were normal and unrestricted, with 4 cases of extensible intramedullary rod displacement.In the Williams intramedullary rod group, there were 30 cases of postoperative ankle joint stiffness and no displacement of the fixation position of the intramedullary rod.There was no statistically significant difference in postoperative complications between the two groups of children (all P>0.05). Conclusions: The use of both extensible intramedullary rods and Williams intramedullary rods in the combined surgery for congenital tibial pseudarthrosis in children can achieve effective internal fixation results. The initial postoperative bone healing rate is high, and there is no difference in the incidence of postoperative complications between groups. Both internal fixation methods have their own advantages and disadvantages, and suitable internal fixation methods can be selected based on the characteristics of the patient.

The polymicrobial infection affects the infection recurrence rate (not failure) in treating femoral and tibial bone defects with the Masquelet technique-a comparative retrospective analysis of 54 patients with mono- and polymicrobial infections.

This study evaluated whether polymicrobial infection affects reoperation rates due to infection recurrence and treatment failure with the Masquelet technique in infected posttraumatic segmental bone defects of the femur and tibia. We retrospectively analyzed patients treated between 2012 and 2021 in two trauma referral centers. We evaluated demographic data, injury, treatment, infection recurrence, failures, and bone healing rates according to whether the infection was mono- or polymicrobial. After uni-bivariate analysis between patients with polymicrobial and monomicrobial infection, we identified the variables associated with infection recurrence and failure through multivariate analysis. We analyzed 54 patients, 30 (55.55%) with tibial and 24 (44.44%) femoral segmental bone defects, with a mean follow-up of 41.7 ± 15.0months. Forty-four (81.48%) presented monomicrobial, and 10 (18.51%) polymicrobial infections. Comparatively, the need for soft tissue reconstruction and the infection recurrence rate was significantly higher in patients with polymicrobial infections. There was no significant difference in the failure rate (20 vs. 6.81% p = 0.23). Multivariable logistic regression analysis identified the polymicrobial infection as the only independent variable associated with infection recurrence (Odds Ratio = 11.07; p = 0.0017). Our analysis suggests that polymicrobial infection is associated with a higher risk of infection recurrence in treating the femur and tibia segmental bone defects with the Masquelet technique. This information can help surgeons to inform patients about this and give them a realistic expectation of the outcome and the possibility of reoperation.

The osteogenic and angiogenic potential of microRNA-26a delivered via a non-viral delivery peptide for bone repair

Bone-related injuries and diseases are among the most common causes of morbidity worldwide. Current bone-regenerative strategies such as auto- and allografts are invasive by nature, with adverse effects such as pain, infection and donor site morbidity. MicroRNA (miRNA) gene therapy has emerged as a promising area of research, with miRNAs capable of regulating multiple gene pathways simultaneously through the repression of post-transcriptional mRNAs. miR-26a is a key regulator of osteogenesis and has been found to be upregulated following bone injury, where it induces osteodifferentiation of mesenchymal stem cells (MSCs) and facilitates bone formation. This study demonstrates, for the first time, that the amphipathic, cell-penetrating peptide RALA can efficiently deliver miR-26a to MSCs in vitro to regulate osteogenic signalling. Transfection with miR-26a significantly increased expression of osteogenic and angiogenic markers at both gene and protein level. Using a rat calvarial defect model with a critical size defect, RALA/miR-26a NPs were delivered via an injectable, thermo-responsive Cs-g-PNIPAAm hydrogel to assess the impact on both rate and quality of bone healing. Critical defects treated with the RALA/miR-26a nanoparticles (NPs) had significantly increased bone volume and bone mineral density at 8 weeks, with increased blood vessel formation and mechanical properties. This study highlights the utility of RALA to deliver miR-26a for the purpose of bone healing within an injectable biomaterial, warranting further investigation of dose-related efficacy of the therapeutic across a range of in vivo models.

Dendronized chitosan hydrogel with GIT1 to accelerate bone defect repair through increasing local neovascular amount

Bone defects have long been a major healthcare issue because of the difficulties in regenerating bone mass volume and the high cost of treatment. G protein-coupled receptor kinase 2 interacting protein 1 (GIT1) has been proven to play an important role both in vascular development and in bone fracture healing. In this study, a type of thermoresponsive injectable hydrogel from oligoethylene glycol-based dendronized chitosan (G1-CS) was loaded with GIT1-plasmids (G1-CS/GIT1), and used to fill unicortical bone defects. RT-PCR analysis confirmed that G1-CS/GIT1 enhanced DNA transfection in MSCs both in vitro and in vivo. From the results of micro-CT, RT-PCR and histological analysis, it can be concluded that G1-CS/GIT1 accelerated the bone healing rate and increased the amount of neovascularization around the bone defects. In addition, an adeno-associated virus (AAV)-GIT1 was constructed to transfect mesenchymal stem cells. The results of capillary tube formation assay, immunofluorescence staining and western blot analysis proved that high expression of GIT1 induces mesenchymal stem cells to differentiate into endothelial cells. RT-PCR analysis and capillary tube formation assay confirmed that the Notch signaling pathway was activated in the differentiation process. Overall, we developed an efficient strategy through combination of injectable hydrogel and G1T1 for bone tissue engineering.

Comparative analysis of cancellous graft and cortico-cancellous graft in osteosynthesis of scaphoid pseudoarthrosis with plate.

Scaphoid is the most fractured carpal bone, with a 5-10% nonunion rate. Treatment challenges include choosing the implant and graft that best corrects humpback deformity and carpal malalignment with higher chances of bony healing. Compare cortico-cancellous and cancellous grafts between two groups of patients treating scaphoid nonunion with locking plates using autologous bone graft and evaluate bone healing rates and radiographic, tomographic, and functional parameters before and after surgery. Non-randomized prospective study including 20 cases of scaphoid nonunion. Groups were divided into Group A (ten patients treated with cortico-cancellous iliac graft) and Group B (ten patients treated with cancellous iliac graft). Patients underwent pre- and postoperative radiographs, computed tomography, and functional evaluation. In postoperative analysis, Group A showed a statistically significant difference in intrascaphoid angle (p = 0.002) and scapholunate angle (p = 0.011) correction when comparing the pre- and postoperative periods. Group B showed a statistically significant difference in intrascaphoid angle (p = 0.002) and scapholunate angle correction (p = 0.0018), grip strength (p = 0.002), and tip pinch strength (p = 0.001) when comparing the pre- and postoperative periods. By comparing both groups, Group B showed a statistically significant difference in intrascaphoid angle correction (p = 0.002), grip strength (p = 0.002), tip pinch strength (p = 0.002), and radial deviation (p = 0.0003). There was no statistical difference when comparing bony healing between groups. Scaphoid nonunion treatment with a locking plate was effective, showing a high bony healing rate and improved carpal alignment in imaging tests for both graft types. However, results for intrascaphoid angle correction, grip strength, tip pinch strength, and radial deviation were better in Group B. IV, case series.

Recent advances in the development of Mg-Ca-Zn alloys as biodegradable orthopedic implants

Development of biodegradable orthopedic implants has gathered significant attention around the globe as it eliminates the second implant removal surgery after bone healing. Mg based alloys are most sought-after materials for these applications however the imbalance between the rate of bone healing and rate of degradation of Mg alloys poses a main challenge for their clinical success. Mg-Ca-Zn alloys possess potential properties to be adopted as biodegradable orthopedic implants. This review presents an overview on the properties and performance of Mg-Ca-Zn alloys. First, Mg-Ca and then Mg-Ca-Zn system is discussed. The effects of manufacturing processes, alloying elements, heat treatments on microstructure, mechanical and corrosion properties of these systems are presented. The effects of surface modification on the corrosion behavior of Mg-Ca-Zn alloys are also discussed in this review. The aim of this review is to coherently present the various scattered results on the development of Mg-Ca-Zn alloys for orthopedic implant applications.

Radiographic Evaluation of Bone Healing Following Oral Administration of Bone Broth and Quail Eggs on Experimentally Drilled Femoral Bone Defect in Rabbits

Introduction: Radiography can monitor bone healing to detect delayed healing, non-union, and mal-union early. This study aimed to monitor bone healing, following oral administration of quail eggs and bone broth (BB) on a bone defect in the rabbit model.&#x0D; Materials and methods: A total of 24 adult white New Zealand rabbits were used in the study. They were divided into four six groups before creating a 3.5 mm bone defect. The first group received a daily oral dose of BB, the second group a daily oral dose of quail egg (QE), and the third group received a daily oral dose combination of BB and quail eggs (BQE). At the same time, the fourth group was given an oral daily dose of distilled water (CN) for 12 weeks. Radiographs were taken at 2, 4, 6, 8, 10, and 12 weeks postoperative. An experienced radiologist blinded to the groupings scored the radiographs on a scale of 0-4 based on mineral opacity.&#x0D; Results: At week 6, the BB and BQE groups differed significantly from the QE and CN groups. There was a significant difference between the treatments and the control group at weeks 8 and 10. The complete healing of BB and BQE groups occurred before week 10. The healing of two rabbits in the QE group was done before week 10 although the others completed healing before week 12. The CN group did not heal even after week 12.&#x0D; Conclusion: Using radiography, Monitoring the bone healing rate was done successfully. The BQE group showed the fastest healing, followed by BB, and QE groups.

Antibacterial PLA/Mg composite with enhanced mechanical and biological performance for biodegradable orthopedic implants

Biodegradability, bone-healing rate, and prevention of bacterial infection are critical factors for orthopedic implants. Polylactic acid (PLA) is a good candidate biodegradable material; however, it has insufficient mechanical strength and bioactivity for orthopedic implants. Magnesium (Mg), has good bioactivity, biodegradability, and sufficient mechanical properties, similar to that of bone. Moreover, Mg has an inherent antibacterial property via a photothermal effect, which generates localized heat, thus preventing bacterial infection. Therefore, Mg is a good candidate material for PLA composites, to improve their mechanical and biological performance and add an antibacterial property. Herein, we fabricated an antibacterial PLA/Mg composite for enhanced mechanical and biological performance with an antibacterial property for application as biodegradable orthopedic implants. The composite was fabricated with 15 and 30 vol% of Mg homogeneously dispersed in PLA without the generation of a defect using a high-shear mixer. The composites exhibited an enhanced compressive strength of 107.3 and 93.2 MPa, and stiffness of 2.3 and 2.5 GPa, respectively, compared with those of pure PLA which were 68.8 MPa and 1.6 GPa, respectively. Moreover, the PLA/Mg composite at 15 vol% Mg exhibited significant improvement of biological performance in terms of enhanced initial cell attachment and cell proliferation, whereas the composite at 30 vol% Mg showed deteriorated cell proliferation and differentiation because of the rapid degradation of the Mg particles. In turn, the PLA/Mg composites exerted an antibacterial effect based on the inherent antibacterial property of Mg as well as the photothermal effect induced by near-infrared (NIR) treatment, which can minimize infection after implantation surgery. Therefore, antibacterial PLA/Mg composites with enhanced mechanical and biological performance may be a candidate material with great potential for biodegradable orthopedic implants.

Spontaneous immunomodulation and regulation of angiogenesis and osteogenesis by Sr/Cu-borosilicate glass (BSG) bone cement to repair critical bone defects

Injectable bone biomaterials like bone cement should be designed and fabricated with certain biological criteria, which include: 1) recruitment and polarization of the macrophages from M1 (pro-inflammatory) to M2 (anti-inflammatory) phenotype, 2) enhance vascularization, and 3) activate osteogenic differentiation of bone marrow-derived stem cells to promote bone healing. So far, no injectable biomaterials could spontaneously regulate the entire bone healing process that involves inflammation, angiogenesis, and osteogenesis. Therefore, in this study, we designed bone cement comprised of strontium and copper-incorporated borosilicate glass (Sr/Cu-BSG) in the liquid phase of chitosan to modulate bone healing. In vitro studies showed that the controlled release of Sr and Cu ions up-regulated anti-inflammatory genes(IL-1Ra and TGF-β1) while down-regulating pro-inflammatory genes(IL-1β and IL-6) in macrophages at 3 days. Sr and Cu ions also increased the expressions of angiogenic genes (VEGF and bFGF) in HUVECs at 5 days and osteogenic genes (Runx-2, OCN, and OPN) in hBMSCs at 7, 14, and 21 days. 5Sr3Cu-BSG bone cement exhibited the best anti-inflammatory, angiogenic, and osteogenic properties among the bone cement groups with different Sr and Cu ratios. Short-term and long-term implantation of Sr/Cu-BSGs in femoral condylar bone defects of rats and rabbits confirmed the in vitro results, where the degradation rate of Sr/Cu-BSG matched the bone healing rate. Similar to in vitro, the 5Sr3Cu-BSG group also showed the highest bone formation in vivo. Excellent physical and chemical properties, along with its bone repairing ability, make the Sr/Cu-BSG bone cement a good candidate biomaterial for treating bone defects.

Split dCas12a activator for lncRNA H19 activation to enhance BMSC differentiation and promote calvarial bone healing

Healing of large calvarial bone defects in adults is challenging. We previously showed that inducing chondrogenic differentiation of mesenchymal stem cells from bone marrow (BMSC) or adipose tissue (ASC) before implantation can switch the repair pathway and improve calvarial bone healing. Split dCas12a activator is a new CRISPR activation system comprising the amino (N) and carboxyl (C) fragments of dCas12a protein, each being fused with synthetic transcription activators at both termini. The split dCas12a activator was shown to induce programmable gene expression in cell lines. Here we exploited the split dCas12a activator to activate the expression of chondroinductive long non-coding RNA H19. We showed that co-expression of the split N- and C-fragments resulted in spontaneous dimerization, which elicited stronger activation of H19 than full-length dCas12a activator in rat BMSC and ASC. We further packaged the entire split dCas12a activator system (13.2 kb) into a hybrid baculovirus vector, which enhanced and prolonged H19 activation for at least 14 days in BMSC and ASC. The extended H19 activation elicited potent chondrogenic differentiation and inhibited adipogenesis. Consequently, the engineered BMSC promoted in vitro cartilage formation and augmented calvarial bone healing in rats. These data implicated the potentials of the split dCas12a activator for stem cell engineering and regenerative medicine.

Bioinspired Mild Photothermal Effect-Reinforced Multifunctional Fiber Scaffolds Promote Bone Regeneration.

Bone fractures are often companied with poor bone healing and high rates of infection. Early recruitment of mesenchymal stem cells (MSCs) is critical for initiating efficient bone repair, and mild thermal stimulation can accelerate the recovery of chronic diseases. Here, a bioinspired, staged photothermal effect-reinforced multifunctional scaffold was fabricated for bone repair. Uniaxially aligned electrospun polycaprolactone nanofibers were doped with black phosphorus nanosheets (BP NSs) to endow the scaffold with excellent near-infrared (NIR) responsive capability. Apt19S was then decorated on the surface of the scaffold to selectively recruit MSCs toward the injured site. Afterward, microparticles of phase change materials loaded with antibacterial drugs were also deposited on the surface of the scaffold, which could undergo a solid-to-liquid phase transition above 39 °C, triggering the release of payload to eliminate bacteria and prevent infection. Under NIR irradiation, photothermal-mediated up-regulation of heat shock proteins and accelerated biodegradation of BP NSs could promote the osteogenic differentiation of MSCs and biomineralization. Overall, this strategy shows the ability of bacteria elimination, MSCs recruitment, and bone regeneration promotion with the assistance of photothermal effect in vitro and in vivo, which emphasizes the design of a bioinspired scaffold and its potential for a mild photothermal effect in bone tissue engineering.

Definitive fixation in the first stage of the induced membrane technique for septic segmental bone defects. Why not?

BackgroundInfected segmental bone defects (I-SBD) are challenging and complex to manage. This study aimed to show the outcomes achieved in I-SBD of the femur and tibia, treated with the induced membrane technique performing a definitive bone stabilization in the first stage. MethodsWe retrospectively reviewed 30 patients with infected non-articular segmental bone defects of the femur (n = 11) and tibia (n = 19), operated consecutively between January 2015 and May 2021. The need for fixation exchange, bone defect length, allo/autograft ratio used, bone healing, reoperation (discriminating between mechanical and infection-related causes), and failure rates (graft resorption or nonunion) were recorded. ResultsFixation in the first stage was performed with 28 (93.33%) intramedullary nails, ten coated with antibiotic cement, and 2 (6.67%) locked plates. None were removed during the second stage of the technique. The mean length of the bone defects was 5cm (range 3.5–12). The most commonly used allo-/autograft ratio was 50-50. The bone healing rate was 93.33% (n = 28), with a median follow-up of 7 months (range 3–12). The reoperation rate due to mechanical instability was 3.33% (n = 1) and for recurrence of infection was 10.0% (n = 3). The overall failure rate was 6.67% (n = 2). The median follow-up was 42 months (range 12–85). ConclusionMasquelet technique appears feasible and effective in treating infected segmental bone defects of the femur and tibia. Definitive fixation at the first stage showed a success rate of 93.33%, with a re-operation rate of 10.0% related to infection.

Clinical and radiological outcome of Mason-Johnston types III and IV radial head fractures treated by an on-table reconstruction

BackgroundOnly few methods treating comminuted radial head fractures have been established providing sufficient joint reconstruction, restoring radial length and enabling early joint mobilization. When an anatomical reconstruction using open reduction and internal fixation is not possible, radial head resection or primary arthroplasty is often conducted. An “Ex situ/on-table” reconstruction is widely disregarded but can be an option. The purpose of this study was to evaluate the functional and radiological outcome of comminuted radial head fractures treated with an “on-table” reconstruction and internal fixation using a low profile plate.MethodsFourteen patients who sustained a radial head fracture (9 Mason-Johnston type III and 5 Mason-Johnston type IV) and were treated with an “on-table” reconstruction between 2010 and 2020 were evaluated retrospectively. The patients mean age was 41.3 years (range 21–69). The clinical evaluation included active range of motion, grip strength, pain level and elbow stability. The functional outcome was assessed using the Disability of Arm, Shoulder and the Hand (DASH) score, Mayo Elbow Performance Index (MEPI), Broberg and Morrey score. The radiological examination included a.p. and lateral views of the injured elbow to evaluate nonunions, loss of reduction, joint alignment, avascular radial head necrosis, heterotopic ossifications and posttraumatic osteoarthritis.ResultsThe inclusion rate was 74% with a mean follow-up of 50 months (range 16–128). The mean elbow flexion of the injured side was 126° (range110–145°) with an average extension loss of 8° (range 0–40°). Pronation was 65° (15–90°) and supination 66° (5–90°). The mean MEPI was 87 points (range 45–100). The mean DASH score was 13 points (range 1–88). According to the Broberg and Morrey functional scoring system, the average score was 92 points (range 88–100). Complete bone union was achieved in 9 cases, partial union in 4 cases and nonunion in one case. There were no signs of avascular necrosis of the radial head. Signs of post-traumatic osteoarthritis were seen in 11 cases. Five patients needed an implant removal due to a radio-ulnar impingement and one patient a revision surgery due to the nonunion and implant breakage.ConclusionsAn on-table (ex situ) reconstruction of the radial head is a reliable option with a good clinical outcome and low complication rate in the surgical treatment of comminuted radial head fractures. It can restore joint alignment and maintain radial length. The risk for avascular necrosis is neglectable, and the bone healing rate is high.

Maxillary and Mandibular Healing after Facial Allotransplantation

PURPOSE: Facial transplantation has emerged as a viable option in treating devastating facial injuries. Despite the high healing rate of Le Fort I-II-III and bilateral sagittal split osteotomies (BSSO) in non-transplant patients (with reported non-union rates of 1.6% and 2.6%, respectively),[1,2] previous studies have reported nonunion between the allograft and the recipient’s bone at the area of maxillary and mandibular osteotomies. [3,4] This suboptimal bone healing remains unexplained and is still yet to be investigated. In this study, we present three patients that received facial transplantation at our institution with a focus on the healing of the mandibular and maxillary osteotomies after osteocutaneous face transplantation. METHOD: A retrospective chart review was conducted of facial allotransplantation patients at the Cleveland Clinic from December 2008 to inception. Demographics such as age, date of birth, and sex were recorded. Additional variables included procedures, revisions, reoperations, medications, and bone stability and healing. Computed tomography (CT) images assessed alignment of skeletal components, bony union quality, and stability of fixation. RESULTS: Three patients receiving facial allotransplantation at our institution were included in our study: two had Le Fort III segment transplantation, and one had transplantation of both a Le Fort III segment and mandibular BSSO. The Le Fort III segment in all three patients exhibited mobility and fibrous union at the Le Fort III osteotomy on CT. In contrast, the BSSO healed uneventfully after transplantation and revision surgery, with bony union confirmed by both CT and histology of the fixation area between the donor and recipient mandible bilaterally. No patients with midfacial fibrous union required revision of the nonunion as they were clinically asymptomatic. CONCLUSION: Le Fort osteotomies demonstrated inferior healing in patients undergoing facial transplantation compared to Le Fort osteotomies in patients treated for malocclusion. Interestingly, the mandible healed uneventfully after facial transplantation, likely due to the amount of rich cancellous bone in the mandible. This similarly reflects bone healing rates in patients undergoing mandibular surgery for correction of malocclusion or hand transplantation at the level of the humerus, radius, and ulna. Nonunion of the midface does not require revision unless the patient is clinically symptomatic. REFERENCES: 1. Imholz B, Richter M, Dojcinovic I, and Hugentobler M, Non-union of the maxilla: a rare complication after Le Fort I osteotomy. Revue de stomatologie et de chirurgie maxillo-faciale. 2010; 111(5-6): p. 270-275. 2. Chin M and Toth BA, Le Fort III advancement with gradual distraction using internal devices. Plast Reconstr Surg. 1997; 100(4): p. 819-30; discussion 831-2. 3. Lantieri L, Grimbert P, Ortonne N, et al., Face transplant: long-term follow-up and results of a prospective open study. Lancet. 2016; 388(10052): p. 1398-1407. 4. Goutard M, Lellouch AG, Dussol B, and Lantieri LA, Facial Trauma 8 years after a Face Transplantation. Plast Reconstr Surg Glob Open. 2021; 9(5): p. e3575.

Current Research Studies of Mg–Ca–Zn Biodegradable Alloys Used as Orthopedic Implants—Review

Biodegradable alloys and especially magnesium-based alloys are considered by many researchers as materials to be used in medicine due to their biocompatibility and excellent mechanical properties. Biodegradable magnesium-based materials have applications in the medical field and in particular in obtaining implants for small bones of the feet and hands, ankles, or small joints. Studies have shown that Mg, Zn, and Ca are found in significant amounts in the human body and contribute effectively and efficiently to the healing process of bone tissue. Due to its biodegradability, magnesium alloys, including Mg–Ca–Zn alloys used in the manufacture of implants, do not require a second surgery, thus minimizing the trauma caused to the patient. Other studies have performed Mg–Ca–Zn system alloys with zinc variation between 0 and 8 wt.% and calcium variation up to 5 wt.%, showing high biocompatibility, adequate mechanical properties, and Mg2Ca and Mg6Ca2Zn compounds in microstructure. Biocompatibility is an essential factor in the use of these materials, so that some investigations have shown a cell viability with values between 95% and 99% compared with the control in the case of Mg–0.2Ca–3Zn alloy. In vivo analyses also showed no adverse reactions, with minimal H2 release. The aim of this review includes aspects regarding microstructure analysis and the degradation mechanisms in a specific environment and highlights the biocompatibility between the rate of bone healing and alloy degradation due to rapid corrosion of the alloys.