Early Stages Of Healing Research Articles

Exosomal PD-L1 induces osteogenic differentiation and promotes fracture healing by acting as an immunosuppressant

A moderate inflammatory response at the early stages of fracture healing is necessary for callus formation. Over-active and continuous inflammation, however, impairs fracture healing and leads to excessive tissue damage. Adequate fracture healing could be promoted through suppression of local over-active immune cells in the fracture site. In the present study, we achieved an enriched concentration of PD-L1 from exosomes (Exos) of a genetically engineered Human Umbilical Vein Endothelial Cell (HUVECs), and demonstrated that exosomes overexpressing PD-L1 specifically bind to PD-1 on the T cell surface, suppressing the activation of T cells. Furthermore, exosomal PD-L1 induced Mesenchymal Stem Cells (MSCs) towards osteogenic differentiation when pre-cultured with T cells. Moreover, embedding of Exos into an injectable hydrogel allowed Exos delivery to the surrounding microenvironment in a time-released manner. Additionally, exosomal PD-L1, embedded in a hydrogel, markedly promoted callus formation and fracture healing in a murine model at the early over-active inflammation phase. Importantly, our results suggested that activation of T cells in the peripheral lymphatic tissues was inhibited after local administration of PD-L1-enriched Exos to the fracture sites, while T cells in distant immune organs such as the spleen were not affected. In summary, this study provides the first example of using PD-L1-enriched Exos for bone fracture repair, and highlights the potential of Hydrogel@Exos systems for bone fracture therapy through immune inhibitory effects.

Electrospun Scaffold of Collagen and Polycaprolactone Containing ZnO Quantum Dots for Skin Wound Regeneration.

Nanofibers (NFs) have been widely used in tissue engineering such as wound healing. In this work, the antibacterial ZnO quantum dots (ZnO QDs) have been incorporated into the biocompatible poly (ε-caprolactone)/collagen (PCL/Col) fibrous scaffolds for wound healing. The as-fabricated PCL-Col/ZnO fibrous scaffolds exhibited good swelling, antibacterial activity, and biodegradation behaviors, which were beneficial for the applications as a wound dressing. Moreover, the PCL-Col/ZnO fibrous scaffolds showed excellent cytocompatibility for promoting cell proliferation. The resultant PCL-Col/ZnO fibrous scaffolds containing vascular endothelial growth factor (VEGF) also exhibited promoted wound-healing effect through promoting expression of transforming growth factor-β (TGF-β) and the vascular factor (CD31) in tissues in the early stages of wound healing. This new electrospun fibrous scaffolds with wound-healing promotion and antibacterial property should be convenient for treating wound healing.Supplementary InformationThe online version contains supplementary material available at 10.1007/s42235-021-00115-7.

Application of concentrated growth factor to autotransplantation with inflammation in recipient area

ObjectiveThe purpose of this study was to apply concentrated growth factor (CGF) to the transplanted area with inflammation, to observe the clinical effects of CGF on the inflammation area assisted by 3D printing technology.MethodsA total of 52 compromised mandibular first or second molar with chronic periapical lesions were transplanted with mature third molars. The patients were divided into CGF group (n = 26) and control group (n = 26) and transplanted into fresh extraction sockets with or without CGF. All the patients underwent clinical and radiographic examinations during the follow-up.ResultsAverage surgery and extra-oral time were 39 min (± 7.8) and 42 s (± 10.2). The success rates of CGF group and control group were 100% and 92.3% respectively. Most of the periapical lesions in CGF group healed completely within 3 months, which was significantly faster than control group. The initial stability of CGF group was better than control group immediately after operation, and the degree of pain in CGF group was lower than control group on the 1st and 3rd day after operation.ConclusionsThe application of CGF in recipient site with chronic periapical lesions can accelerate the regeneration of alveolar bone and the healing of inflammation, greatly shorten the healing period. Meanwhile, CGF help to reduce postoperative pain and reaction at the early stage of healing and increase the success rate of autogenous tooth transplantation (ATT). Additionally, the use of 3D printing model can greatly reduce the extra-oral time of donor teeth.

Lipid mediator profiles of burn wound healing: Acellular cod fish skin grafts promote the formation of EPA and DHA derived lipid mediators following seven days of treatment

The use of acellular fish skin grafts (FSG) for the treatment of burn wounds is becoming more common due to its beneficial wound healing properties. In our previous study we demonstarted that FSG is a scaffold biomaterial that is rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) conjugated to phosphatidylcholines. Here we investigated whether EPA and DHA derived lipid mediators are influenced during the healing of burn wounds treated with FSG. Deep partial and full thickness burn wounds (DPT and FT, respectively) were created on Yorkshire pigs (n = 4). DPT were treated with either FSG or fetal bovine dermis while FT were treated either with FSG or cadaver skin initially and followed by a split thickness skin graft. Punch biopsies were collected on days 7, 14, 21, 28 and 60 and analyzed in respect of changes to approximately 45 derivatives of EPA, DHA, arachidonic acid (AA), and linoleic acid (LA) employing UPLC-MS/MS methodology. Nine EPA and DHA lipid mediators, principally mono-hydroxylated derivatives such as 18-HEPE and 17-HDHA, were significantly higher on day 7 in the DPT when treated with FSG. A similar but non-significant trend was observed for the FT. The results suggest that the use of FSG in burn wound treatment can alter the formation of EPA and DHA mono hydroxylated lipid mediators in comparison to other grafts of mammalian origin. The differences observed during the first seven days after treatment indicates that FSG affects the early stages of wound healing.

Pulsed electromagnetic field therapy alters early healing in a rat model of rotator cuff injury and repair: Potential mechanisms.

Rotator cuff repair failure remains common due to poor tendon healing, particularly at the enthesis. We previously showed that pulsed electromagnetic field (PEMF) therapy improved the mechanical properties of the rat supraspinatus tendon postoperatively. However, little is known about the mechanisms behind PEMF-dependent contributions to improved healing in this injury model. The objective of this study was to determine the influence of PEMF treatment on tendon gene expression and cell composition, as well as bone microarchitecture and dynamic bone metabolism during early stages of healing. We hypothesized that PEMF treatment would amplify tendon-healing related signaling pathways while mitigating inflammation and improve bone metabolism at the repair site. Rats underwent rotator cuff injury and repair followed by assignment to either control (non-PEMF) or PEMF treatment groups. Gene and protein expression as well as tendon and bone histological assessments were performed 3, 7, 14, 21, and 28 days after injury. Gene expression data demonstrated an upregulation in the bone morphogenetic protein 2 signaling pathway and increases in pro-osteogenic genes at the insertion, supporting important processes to re-establish the tendon-bone interface. PEMF also downregulated genes related to a fibrotic healing response. Anti-inflammatory effects were demonstrated by both gene expression and macrophage phenotype. PEMF significantly increased the rate of kinetic bone formation directly adjacent to the tendon enthesis as well as the number of cuboidal surface osteoblasts (active osteoblasts) in the humeral head. This study has provided insight into how PEMF affects cellular and molecular processes in the supraspinatus tendon and adjacent bone after injury and repair.

Differences in artificial ligament graft osseointegration of the anterior cruciate ligament in a sheep model: a comparison between interference screw and cortical suspensory fixation.

BackgroundInterference screws are the most common femoral fixation for anterior cruciate ligament (ACL) reconstruction with polyethylene terephthalate (PET) artificial ligaments. However, interference screws have several disadvantages, such as the risk of one tunnel blowout and damage to the graft. Suspensory fixations have the advantages of high tensile strength and promotion of graft bone contact. The purpose of this study was to compare PET artificial ligament graft osseointegration between interference screw fixation (ISF) and cortical suspensory fixation (CSF) for ACL reconstruction.MethodsForty sheep underwent ACL reconstruction of the right knee with PET artificial ligament. The graft was fixed with ISF or CSF for femoral fixation. Animals were randomly assigned to the ISF (n=20) or the CSF (n=20) groups. The sheep were sacrificed at 3 or 12 months postoperatively for biomechanical tests, micro computed tomography (micro-CT) scans, and histological assessments.ResultsThe mean load-to-failure between the CSF group (836±355 N) appeared higher than that of the ISF group (604±277 N) at 3 months, but no significant difference was detected between the groups (P=0.24). At 12 months, there was also no significant difference in load-to-failure between the CSF and ISF groups (1,194±350 vs. 1,097±764 N; P=0.78). According to the micro-CT scan results, the femoral bone tunnel diameter of the ISF group appeared larger than that of the CSF group at 3 months (12±1 vs. 10±1 mm; P=0.02) and similar to that of the CSF group at 12 months (12±1 vs. 11±2 mm; P=0.38). Furthermore, histological results showed that at the graft-tunnel interface of the femoral tunnel aperture, disoriented fibers formed in the ISF group while oriented and dense fibers formed in the CSF group.ConclusionsACLR with synthetic ligament by cortical suspension devices with adjustable loops demonstrated a better graft-bone healing capacity at the femoral tunnel aperture compared with that from titanium interference screws over 12 months postoperatively. No significant difference was found in biomechanical strength between the two fixation methods during the early healing stage.

The effects of a proprietary Manuka honey and essential oil hydrogel on the healing of acute full‐thickness wounds in dogs

To evaluate the effect of a proprietary Manuka honey essential oil hydrogel on the healing of acute, full-thickness wounds in dogs. Prospective, controlled, randomized, experimental study. Purpose-bred, adult, female beagles (n = 10). Two 2 × 2cm surgical wounds were created bilaterally on the trunk of each dog; each side was randomized to receive HoneyCure® (HOC) or standard-of-care (CON) dressings. Cranial wounds were for histopathological analysis and the caudal wounds for culture and planimetry. Total and open wound areas were measured with digital image planimetry at 15 time points. From these data, percent contraction and percent epithelialization were calculated. Tissue biopsies were obtained at 7 time points and histologic features scored. Cultures were obtained at 2 time points. Epithelialization was 11.7, 10.4, and 10.1 percentage points higher in HOC wounds compared to CON wounds at days 16, 18, and 21 respectively. Wound contraction and histological scores did not differ between groups. Cultures were positive in 7/40 (17.5%) wounds, with Staphylococcus pseudintermedius and Staphylococcus epidermidis isolated evenly. There was no difference of infection rate between the two groups; all infections were superficial and did not require treatment. This study did not provide evidence to support the application of HoneyCure® in small, acute wounds in healthy dogs. However, application may be beneficial in the early proliferative stage of wound healing and in wounds that would benefit from early, robust epithelialization.

In Vivo Analyses of Osteogenic Activity and Bone Regeneration Capacity of Demineralized Freeze-Dried Bovine Bone Xenograft: A Potential Candidate for Alveolar Bone Fillers.

Background Deproteinized bovine bone mineral (DBBM) particle is the commonly used bone graft substitute in implant surgery which is mainly osteoconductive and has very slow degradation. Demineralized freeze-dried bovine bone xenograft (DFDBBX) particle is being developed as a novel xenogeneic bone filler. Objectives The study aimed to analyze osteogenic activity and bone-forming capacity of DFDBBX particles compared to DBBM particles in alveolar bone defects in rabbit mandibles models. Material and Methods. This study investigated bone defects whether filled with DBBM particles or DFDBBX particles or left unfilled in 30 rabbit mandibles. Specimens were processed for histology, immunohistochemistry, and micro-CT scanning. Statistical difference was set at a p value < 0.05. Results The quantitative assessment showed a significantly lower number of osteoclasts and a higher number of osteoblasts in the DFDBBX group compared to the DBBM group in 2 and 4 weeks (p < 0.05). Immunostaining analyses showed significantly higher expression of RUNX2, collagen type I, alkaline phosphatase, and osteocalcin in the DFDBBX group compared to the DBBM group in 2 and 4 weeks. Bone healing score in the DFDBBX group was comparable to the DBBM group. Micro-CT presented no significant difference in the volume percentage of the mineralized tissue in the DBBM and DFDBBX groups in spite of the different healing patterns in both groups. Conclusion DFDBBX particles induced higher osteoblastic activities than DBBM particles at the early stage of healing. Meanwhile, the capacity of bone formation in DFDBBX particles was comparable with DBBM particles at the later stage of healing. Considering the limitation of this study, the results presented DFDBBX particles as potential bone filler candidates.

Patient-reported outcome measures and clinical outcomes following peri-implant vestibuloplasty with a free gingival graft versus xenogeneic collagen matrix: a comparative prospective clinical study

BackgroundThe objective of this study was to compare patient-reported outcome measures (PROMs) and clinical outcomes after augmentation with xenogeneic collagen matrix (XCM) or free gingival graft (FGG) during different postoperative phases.MethodsForty-two patients (21 per group) with keratinized mucosa width (KMW) of < 2 mm at buccal implant sites in the posterior mandible were enrolled. All underwent vestibuloplasty and were allocated to either FGG (control) or XCM (test) group. Intraoperative morbidity of pain, stress, nausea, tolerance to time, and acceptance of surgery were evaluated immediately after surgery. The severity and duration of subjective pain, swelling, and bleeding were compared within a 2-week postoperative period. The willingness to retreat and satisfaction were assessed at 6 months. All PROMs were obtained using questionnaires and visual analog scales. The buccal KMW and other peri-implant parameters were also evaluated.ResultsNo significant between-group differences were observed in PROMs immediately after surgery, except acceptance of surgery (0, 0–30.0 vs. 30, 0–50.0, p = 0.025). At 2 weeks, pain severity (46.7 ± 25.9 vs 61.9 ± 20.2, p = 0.040) and duration (5.52 ± 3.57 vs 8.48 ± 2.80, p = 0.005) were significantly lower in the test group, and pain perception during speaking and chewing was significantly higher for FGG, with no significant between-group differences in swelling and bleeding. At 6 months, the test group showed a higher willingness to retreat (76% vs 43%, p = 0.021); however, satisfaction with treatment outcomes was similar in both groups. At 6 months, the gain of KMW was significantly higher in FGG than in XCM (XCM: 1.57 ± 1.69 mm, FGG: 2.68 ± 1.80 mm, p = 0.003). Other peri-implant parameters did not show significant differences.ConclusionsWithin the limitation of the present nonrandomized study, XCM demonstrated more positive PROMs than FGG during different postoperative phases, mainly for less pain perception during the early healing stage, but was inferior to FGG in terms of gain of KMW. For KMW augmentation in the posterior mandible, XCM may be indicated when patients can bear little pain.Clinical trial registrationChiCTR1900022575, date of registration: 17/4/2019, retrospectively registered,

The Role of Adenosine Receptor A2A in the Regulation of Macrophage Exosomes and Vascular Endothelial Cells During Bone Healing.

BackgroundMacrophage exosomes and vascular endothelial cells (VECs) are critical to bone healing. However, few studies explore the molecular regulation of them in the bone fracture microenvironment.MethodsIn this study, we explored the effects of adenosine receptor A2A (ADA2AR) in macrophage exosomes and VECs during bone healing. CGS21680 (an ADA2AR agonist) and ZM241385 (an ADA2AR antagonist) were used. First, the effects of the ADA2AR on VECs during bone healing were studied in vivo in a rat tibial fracture model. Second, the effects of ADA2AR on VECs and in the regulation of VECs by macrophages were examined in the bone fracture microenvironment. Third, the effects of ADA2AR on the regulation of macrophage exosomes on VECs were analyzed. Finally, the genes and long non-coding RNAs (lncRNAs) associated with the regulation of VECs by the ADA2AR were examined by high-throughput sequencing and bioinformatics analysis.ResultsCGS21680 accelerated VEC proliferation in the early stage of bone healing and that ZM241385 suppressed VEC proliferation in vivo. ZM241385 inhibited cell viability and tube formation in vitro. However, CGS21680 did not promote tube formation, cell proliferation, or cell migration in vitro. The inhibition of macrophage exosomes could suppress tube formation and VEC migration. CGS21680 had no effects on tube formation in a macrophage-VEC co-culture. The macrophage exosomes were purified and CGS21680 promoted the macrophage secretion of exosomes. In contrast, ZM241385 inhibited the macrophage secretion exosomes. Finally, the lncRNA and mRNA involved in the activation of the ADA2AR in VECs were analyzed. CGS21680 upregulated 3274 mRNAs and downregulated 2236 mRNAs, and upregulated 1696 lncRNAs and downregulated 1882 lncRNAs. The hub genes involved in angiogenesis were Flt1, Fgf2, Mapk14, Fn1, and Jun.ConclusionThe activation of ADA2AR was essential for angiogenesis and the secretion of exosomes by macrophages during bone healing; moreover, the inactivation of the ADA2AR led to poor angiogenesis and bone nonunion.

Diagnostic prediction of ovine fracture healing outcomes via a novel multi-location direct electromagnetic coupling antenna.

BackgroundExpedient prediction of adverse bone fracture healing (delayed- or non-union) is necessary to advise secondary treatments for improving healing outcome to minimize patient suffering. Radiographic imaging, the current standard diagnostic, remains largely ineffective at predicting nonunions during the early stages of fracture healing resulting in mean nonunion diagnosis times exceeding six months. Thus, there remains a clinical deficit necessitating improved diagnostic techniques. It was hypothesized that adverse fracture healing expresses impaired biological progression at the fracture site, thus resulting in reduced temporal progression of fracture site stiffness which may be quantified prior to the appearance of radiographic indicators of fracture healing (i.e., calcified tissue).MethodsA novel multi-location direct electromagnetic coupling antenna was developed to diagnose relative changes in the stiffness of fractures treated by metallic orthopaedic hardware. The efficacy of this diagnostic was evaluated during fracture healing simulated by progressive destabilization of cadaveric ovine metatarsals treated by locking plate fixation (n=8). An ovine in vivo comparative fracture study (n=8) was then utilized to better characterize the performance of the developed diagnostic in a clinically translatable setting. In vivo measurements using the developed diagnostic were compared to weekly radiographic images and postmortem biomechanical, histological, and micro computed tomography analyses.ResultsFor all cadaveric samples, the novel direct electromagnetic coupling antenna displayed significant differences at the fracture site (P<0.05) when measuring a fully fractured sample versus partially intact and fully intact fracture states. In subsequent in vivo fracture models, this technology detected significant differences (P<0.001) in fractures trending towards delayed healing during the first 30 days post-fracture.ConclusionsThis technology, relative to traditional X-ray imaging, exhibits potential to greatly expedite clinical diagnosis of fracture nonunion, thus warranting additional technological development.

Limited added value of negative pressure wound therapy compared with calcium alginate dressings for second intention healing in a noncontaminated and contaminated equine distal limb wound model.

Distal limb wounds in horses often show aberrant healing due to a slow inflammatory response. In human medicine, negative pressure wound therapy (NPWT) is used for the treatment of chronic wounds with a similar inflammatory response. To compare the effect of NPWT to calcium alginate dressings on the healing of (non) contaminated equine distal limb wounds. Controlled experiment. Circular wounds were created on the left and right dorsomedial metacarpus of 10 horses. In five horses, the wounds were contaminated with Staphylococcus aureus and Pseudomonas aeruginosa. In all horses, one limb was treated with NPWT, the other with calcium alginate dressings. Treatments were applied during nine days for noncontaminated wounds and six days for contaminated wounds. Noninvasive (clinical assessment, bacteriology swabs, thermographic images and wound dimensions) and invasive (biopsies for histology and growth factor analysis) measurements were taken regularly for 71 and 29days respectively. Effects of selected parameters on continuous dependent variables were analysed using ANOVA, while for discrete dependent variables, logistic regression was applied. In noncontaminated wounds, there was significantly less wound retraction in the early healing stages when treated with NPWT (mean difference [95% CI]=19.2% [13.3%-25.1%]; P=.005), although wound size was not significantly different between NPWT and control wounds at later healing stages. Noncontaminated control wounds had a significantly higher neutrophil influx (OR [95% CI]=1.99 [1.49-2.66]; P<.001) and lower macrophage influx (OR [95% CI]=0.75 [0.60-0.93]; P=.008) compared with NPWT-treated wounds. Bacterial load and the presence of growth factors did not differ between treatments in noncontaminated wounds. In contaminated wounds, no differences between treatments were observed in wound size, histological parameters, bacterial load or growth factor concentration. Sample size is small. No long-term advantage was detected with NPWT compared with calcium alginate dressings in noncontaminated or contaminated equine distal limb wounds healing by second intention.

Parathyroid hormone promotes cartilage healing after free reduction of mandibular condylar fractures by upregulating Sox9.

After high fractures of the mandibular condyle, the insufficient blood supply to the condyle often leads to poor bone and cartilage repair ability and poor clinical outcome. Parathyroid hormone (PTH) can promote the bone formation and mineralization of mandibular fracture, but its effects on cartilage healing after the free reduction and internal fixation of high fractures of the mandibular condyle are unknown. In this study, a rabbit model of free reduction and internal fixation of high fractures of the mandibular condyle was established, and the effects and mechanisms of PTH on condylar cartilage healing were explored. Forty-eight specific-pathogen-free (SPF) grade rabbits were randomly divided into two groups. In the experimental group, PTH was injected subcutaneously at 20 µg/kg (PTH (1-34)) every other day, and in the control group, PTH was replaced with 1 ml saline. The healing cartilages were assessed at postoperative days 7, 14, 21, and 28. Observation of gross specimens, hematoxylin eosin staining and Safranin O/fast green staining found that every-other-day subcutaneous injection of PTH at 20 µg/kg promoted healing of condylar cartilage and subchondral osteogenesis in the fracture site. Immunohistochemistry and polymerase chain reaction showed that PTH significantly upregulated the chondrogenic genes Sox9 and Col2a1 in the cartilage fracture site within 7-21 postoperative days in the experimental group than those in the control group, while it downregulated the cartilage inflammation gene matrix metalloproteinase-13 and chondrocyte terminal differentiation gene ColX. In summary, exogenous PTH can stimulate the formation of cartilage matrix by triggering Sox9 expression at the early stage of cartilage healing, and it provides a potential therapeutic protocol for high fractures of the mandibular condyle.

The osseointegration and stability of dental implants with different surface treatments in animal models: a network meta-analysis

Dental implants are commonly used to repair missing teeth. The implant surface plays a critical role in promoting osseointegration and implant success. However, little information is available about which implant surface treatment technology best promotes osseointegration and implant stability. The aim of this network meta-analysis was to evaluate the osseointegration and stability of four commonly used dental implants (SLA, SLActive, TiUnite, and Osseotite). The protocol of the current meta-analysis is registered in PROSPERO (International Prospective Register of Systematic Reviews) under the code CRD42020190907 (https://www.crd.york.ac.uk). We conducted a systematic review following PRISMA and Cochrane Recommendations. Medline (PubMed), Cochrane Library, Embase, and the Web of Science databases were searched. Only randomized controlled trials were considered. Twelve studies were included in the current network meta-analysis, eleven studies were included concerning the osseointegration effect and five studies were included for stability analysis (four studies were used to assess both stability and osseointegration). Rank possibility shows that the SLActive surface best promoted bone formation at an early healing stage and TiUnite seemed to be the best surface for overall osseointegration. For stability, TiUnite seemed to be the best surface. The present network meta-analysis showed that the SLActive surface has the potential to promote osseointegration at an early stage. The TiUnite surface had the best effect on osseointegration regarding the overall healing period. The TiUnite surface also had the best effect in stability.

CHANGES IN SUPERIOR DISPLACEMENT, ANGULATION, AND SHORTENING IN THE EARLY PHASE OF HEALING FOR COMPLETELY DISPLACED MIDSHAFT CLAVICLE FRACTURES IN ADOLESCENTS: RESULTS FROM A PROSPECTIVE, MULTICENTER STUDY

Background:Progressive displacement of diaphyseal clavicle fractures has been observed in adult patients, at times necessitating a change from non-operative to operative treatment. Whether this occurs in adolescent patients has not been well investigated.Purpose:The purpose of this study was to assess the rate and extent of progressive clavicle fracture displacement in adolescent patients following injury and during the early stages of healing.Methods:This was an IRB approved multi-center study evaluating prospective data that had previously been collected as part of a larger study evaluating the functional outcomes of adolescent clavicle fractures. A consecutive series of completely displaced diaphyseal clavicle fractures in patients age 10-18 years treated at one of three tertiary care pediatric trauma centers were included; all of which had standardized imaging within 2 weeks of the date of injury and throughout the course of healing (5-20 weeks post-injury). Measurements of clavicle shortening, superior displacement, and angulation were performed using validated techniques. Progressive displacement and/or interval improvement in fracture alignment were noted, as well as the subsequent need for surgical intervention. Patient demographic and radiographic parameters were assessed as possible risk factors for interval displacement.Results:One hundred patients met the inclusion criteria. The mean shortening, superior displacement, and angulation at the time of injury were 24 mm, 15 mm, and 7°, respectively. At a mean of 10 weeks post-injury, the fracture alignment improved across all three measurements for the overall cohort, with mean improvements in shortening of 15%, superior displacement of 15%, and angulation of 21% (Figures 1,2,3) Using a clinical threshold of a change in shortening or displacement of 10 mm or angulation of 10 degrees, 21% of fractures improved, 4% worsened, and 75% remain unchanged. Patients with more severe fractures were more likely to have improved alignment than less displaced fractures (p<0.001). No patient underwent surgical intervention for progressive displacement.Conclusions:Significant early improvements in fracture alignment were observed in a substantial percentage of adolescent patients with completely displaced clavicle fractures. Among the most severely displaced fractures, a 20% improvement in shortening and 50% improvement in angulation was identified. In 4% of cases, increased displacement was observed, but this tended to be mild, and in no cases did it prompt surgical intervention. This finding indicates that the true final deformity after an adolescent clavicle fracture is commonly less than that present at the time of injury.Figures:Figure 1.Figure 2.Figure 3.

Calcitonin Gene-Related Peptide Influences Bone-Tendon Interface Healing Through Osteogenesis: Investigation in a Rabbit Partial Patellectomy Model.

Background:Calcitonin gene-related peptide (CGRP), which has been shown to play an important role in osteogenesis during fracture repair, is also widely distributed throughout the tendon and ligament. Few studies have focused on the role of CGRP in repair of the bone-tendon interface (BTI).Purpose:To explore the effect of CGRP expression on BTI healing in a rabbit partial patellectomy model.Study Design:Controlled laboratory study.Methods:A total of 60 mature rabbits were subjected to a partial patellectomy and then randomly assigned to CGRP, CGRP-antagonist, and control groups. In the CGRP-antagonist group, the CGRP receptor antagonist BIBN4096BS was administered to block CGRP receptors. The patella–patellar tendon complex was harvested at 8 and 16 weeks postoperatively and subjected to radiographic, microlaser Raman spectroscopy, histologic, and biomechanical evaluation.Results:Radiographic data showed that local CGRP expression improved the growth parameters of newly formed bone, including area and volumetric bone mineral density (P < .05 for both). Raman spectroscopy revealed that the relative bone mineral composition increased in the CGRP group compared with in the control group and the CGRP-antagonist group (P < .05 for both). Histologic testing revealed that the CGRP group demonstrated better integration, characterized by well-developed trabecular bone expansion from the residual patella and marrow cavity formation, at the 8- and 16-week time points. Mechanical testing demonstrated that the failure load, ultimate strength, and stiffness in the CGRP group were significantly higher than those in the control group (P < .05 for all), whereas these parameters in the CGRP-antagonist group were significantly lower compared with those in the control group at 16 weeks after surgery (P < .05 for all).Conclusion:Increasing the local concentration of CGRP in the early stages of BTI healing enhanced osteogenesis in a rabbit partial patellectomy model and promoted healing of the BTI injury, whereas treatment using a CGRP antagonist had the opposite effect. However, exogenous CGRP expression did not induce novel bone remolding.Clinical Relevance:CGRP may have potential as a new therapy for BTI injuries or may be added to postoperative regimens to facilitate healing.

Early Biological Response of an Ultra-Hydrophilic Implant Surface Activated by Salts and Dry Technology: An In-Vitro Study

The use of dental implants has grown over the years and has led to higher success rates. To further enhance surgical outcomes, many research groups and companies have shifted their focus to surfaces roughness, wettability and chemistry. In a recent study a new dry salt bioactivate surface has been described from a chemical and physical point of view. The aim of this study is to evaluate the osteogenic response of pre-osteoblast cell lines to dry bioactivated surface. MC3T3-E1 osteogenic cell lines were cultured on SM (sandblasted and dual acid-etched surface) and HNS (SM surface with dry salts bioactive technology). Cell adhesion assay, proliferation assay and cell morphology were performed. Osteogenic activity was performed using Alizarin Red S and alkaline phosphatase. The results showed that SM surface determines a slighter but significant increase in cell adhesion and proliferation in a shorter time compared to HNS. On the contrary, HNS surface has long and intertwining filopodia that could be a response to surface HNS-topography that results in a higher stage of differentiation. The nature of the HNS surface is more prone to determine massive deposition of calcium minerals. This study is the first investigating the role of this interesting dry-salts bioactive surface during the first phase of healing and its potential biochemical advantage could be validated by future animal studies with the aim of evaluate the rate of bone implant contact in the early stages of healing.

Balance Between Mechanical Stability and Mechano-Biology of Fracture Healing Under Volar Locking Plate.

The application of volar locking plate (VLP) is promising in the treatment of dorsally comminuted and displaced fracture. However, the optimal balance between the mechanical stability of VLP and the mechanobiology at the fracture site is still unclear. The purpose of this study is to develop numerical models in conjunction with experimental studies to identify the favourable mechanical microenvironment for indirect healing, by optimizing VLP configuration and post-operative loadings for different fracture geometries. The simulation results show that the mechanical behaviour of VLP is mainly governed by the axial compression. In addition, the model shows that, under relatively large gap size (i.e., 3-5mm), the increase of FWL could enhance chondrocyte differentiation while a large BPD could compromise the mechanical stability of VLP. Importantly, bending moment produced by wrist flexion/extension and torsion moment produced from forearm rotation could potentially hinder endochondral ossification at early stage of healing. The developed model could potentially assist orthopaedic surgeons in surgical pre-planning and designing post-operation physical therapy for treatment of distal radius fractures.

Scar tissue development using an acoustic medical diagnostic device in patients with purulent inflammatory wounds of the face and neck

The paper presents evidence of the effectiveness and safety of using the acoustic method for predicting scar formation in patients with purulent inflammatory diseases of the face and neck. An acoustic medical diagnostic device was used to develop a prognostic criterion for assessing scar formation in these patients, and factors influencing the scarring process have been determined. Results of this study demonstrated that it is possible to determine the type of scarring at the early stage of wound healing in patients with purulent inflammatory diseases in the face and neck area using an acoustic medical diagnostic device that allows the assessment of the scarring type, prescribing adequate treatment, and taking preventive measures against pathological scarring of tissues.

Candida Oleophila Proliferated and Accelerated Accumulation of Suberin Poly Phenolic and Lignin at Wound Sites of Potato Tubers.

Candida oleophila is a type of biocontrol yeast offering effective postharvest disease control. To the best of our knowledge, the effect of C. oleophila upon the healing of tubers is yet to be studied. The present study addresses the existing knowledge gap by investigating the effect of C. oleophila on wound healing in potato tubers. The results show that C. oleophila colonized and proliferated at the wound sites during the early and intermediate stages of healing. In addition, C. oleophila reduced weight loss of wounded tubers, decreased disease index of inoculated tubers with Fusarium sulphureum, and accelerated accumulation of suberin poly phenolic (SPP) and lignin at wound sites. C. oleophila activated phenylpropanoid metabolism and increased the content of SPP monomers, total phenol, flavonoids, and lignin. Furthermore, the yeast increased H2O2 content as well as peroxidase activity.