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

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

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

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

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

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

Clinical management and innovation in fracture non-union.

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

Requirement of Pdgfrα+ cells for calvarial bone repair.

Platelet-derived growth factor receptor α (PDGFRα) is often considered as a general marker of mesenchymal cells and fibroblasts, but also shows expression in a portion of osteoprogenitor cells. Within the skeleton, Pdgfrα+ mesenchymal cells have been identified in bone marrow and periosteum of long bones, where they play a crucial role in participating in fracture repair. A similar examination of Pdgfrα+ cells in calvarial bone healing has not been examined. Here, we utilize Pdgfrα-CreERTM;mT/mG reporter animals to examine the contribution of Pdgfrα+ mesenchymal cells to calvarial bone repair through histology and single-cell RNA sequencing (scRNA-Seq). Results showed that Pdgfrα+ mesenchymal cells are present in several cell clusters by scRNA-Seq, and by histology a dramatic increase in Pdgfrα+ cells populated the defect site at early timepoints to give rise to healed bone tissue overtime. Notably, diphtheria toxin-mediated ablation of Pdgfrα reporter+ cells resulted in significantly impaired calvarial bone healing. Our findings suggest that Pdgfrα-expressing cells within the calvarial niche play a critical role in the process of calvarial bone repair.

3D-printed Mg-incorporated PCL-based scaffolds improves rotator cuff tendon-bone healing through regulating macrophage polarization.

Introduction: Rotator cuff tear (RCT) is a common shoulder injury impacting mobility and quality of life, while traditional surgeries often result in poor healing. Tissue engineering offers a promising solution, with poly (ε-caprolactone) (PCL) being favored due to its slow degradation, biocompatibility, and non-toxicity. However, PCL lacks sufficient compression resistance. Incorporating Mg, which promotes bone growth and has antibacterial effects, could enhance RCT repair. Methods: The Mg-incorporated PCL-based scaffolds were fabricated using a 3D printing technique. The scaffolds were incorporated with different percentages of Mg (0%, 5%, 10%, 15%, and 20%). The osteogenic activities and anti-inflammatory properties of the scaffolds were evaluated in vitro using human osteoblasts and macrophages. The tissue ingrowth and biocompatibility of the scaffolds were assessed in vivo using a rat model of RCT repair. The ability of the scaffolds to enhance macrophage polarization towards the M2 subtype and inhibit inflammation signaling activation was also investigated. Results: It was found that when incorporated with 10% Mg, PCL-based scaffolds exhibited the optimal bone repairing ability in vitro and in vivo. The in vitro experiments indicated that the successfully constructed 10 Mg/PCL scaffolds enhance osteogenic activities and anti-inflammatory properties. Besides, the in vivo studies demonstrated that 10 Mg/PCL scaffolds promoted tissue ingrowth and enhanced biocompatibility compared to the control PCL scaffolds. Furthermore, the 10 Mg/PCL scaffolds enhanced the macrophages' ability to polarize towards the M2 subtype and inhibited inflammation signaling activation. Discussion: These findings suggest that 3D-printed Mg-incorporated PCL scaffolds have the potential to improve RCT by enhancing osteogenesis, reducing inflammation, and promoting macrophage polarization. The incorporation of 10% Mg into PCL-based scaffolds provided the optimal combination of properties for RCT repair augmentation. This study highlights the potential of tissue engineering approaches in improving the outcomes of RCT repair and provides a foundation for future clinical applications.

Exosomes derived from tendon stem/progenitor cells enhance tendon-bone interface healing after rotator cuff repair in a rat model.

The rate of retear after surgical repair remains high. Mesenchymal stem cells (MSCs) have been extensively employed in regenerative medicine for several decades. However, safety and ethical concerns constrain their clinical application. Tendon Stem/Progenitor Cells (TSPCs)-derived exosomes have emerged as promising cell-free therapeutic agents. Therefore, urgent studies are needed to investigate whether TSPC-Exos could enhance tendon-bone healing and elucidate the underlying mechanisms. In this study, TSPC-Exos were found to promote the proliferation, migration, and expression of fibrogenesis markers in BMSCs. Furthermore, TSPC-Exos demonstrated an ability to suppress the polarization of M1 macrophages while promoting M2 macrophage polarization. In a rat model of rotator cuff repair, TSPC-Exos modulated inflammation and improved the histological structure of the tendon-bone interface, the biomechanical properties of the repaired tendon, and the function of the joint. Mechanistically, TSPC-Exos exhibited high expression of miR-21a-5p, which regulated the expression of PDCD4. The PDCD4/AKT/mTOR axis was implicated in the therapeutic effects of TSPC-Exos on proliferation, migration, and fibrogenesis in BMSCs. This study introduces a novel approach utilizing TSPC-Exos therapy as a promising strategy for cell-free therapies, potentially benefiting patients with rotator cuff tear in the future.

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

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

Isomangiferin promotes the migration and osteogenic differentiation of rat bone marrow mesenchymal stem cells.

Delayed or failed bone healing is a significant clinical challenge worldwide. Bone marrow mesenchymal stem cells (BMSCs) offer a promising approach for improving fracture healing. Isomangiferin, a xanthone C-glucoside, is known for its pharmacological activities, but its role in fracture healing remains unclear. In this study, we investigated the effects of isomangiferin on BMSCs under oxidative stress conditions induced by hydrogen peroxide (H2O2). Our results showed that isomangiferin promotes osteogenic differentiation and migration of H2O2-treated BMSCs, reduces apoptosis and reactive oxygen species production, and activates the AMP-activated protein kinase/acetyl-CoA carboxylase (AMPK/ACC) pathway. These findings suggest that isomangiferin may be a potential therapeutic agent for enhancing bone healing by modulating BMSC function.

Experimental long bone fracture healing in goats with cockle shell-based calcium carbonate bone paste.

Long bone fractures are common orthopedic conditions. There are numerous ways to repair these fractures. Bone grafting becomes necessary when a broken bone has a significant gap. However, due to insufficient donor volume and donor site morbidity, substitutes are required. In veterinary orthopaedics, calcium carbonate from cockle shells could be used as a bone biomaterial. We investigated its efficacy as a bone biomaterial repair for goat femoral fractures. The study included 10 healthy adult male Black Bengal goats weighing 8 kg and aged 12-13 months. The study includes control and treatment groups. Intramedullary pinning stabilized an 8-mm right femur diaphyseal fracture in the treatment and control groups. The treated group received 2 ml of bone paste in the fractured gap, whereas the control group left it empty. We examined all goats with X-rays on the 7th, 45th, and 60th days, followed by gross and histological findings. Due to callus bridging, radiographs revealed faster bone growth in the treated group than in the control group. Gross examination demonstrates the treated group had a larger fracture callus than the control group. Histopathology showed that bone formed faster and included more osteocytes, osteoblasts, osteoclasts, and bony spicules than in the control group. The treated group had more periosteum osteoblasts, while the control group had fibroblasts. These results showed that the treated group had more osteogenic activity than the control group. This study demonstrates the potential of cockle shell-based calcium carbonate bone paste as a synthetic biomaterial for healing long bone fractures in goats.

Non-steroidal anti-inflammatory drugs in postoperative hand fracture management: Do they positively or negatively impact recovery?

This editorial explores the impact of non-steroidal anti-inflammatory drugs (NSAIDs) on postoperative recovery in hand fracture patients, amidst shifting pain management strategies away from opioids due to their adverse effects. With hand fractures being significantly common and postoperative pain management crucial for recovery, the potential of NSAIDs offers a non-addictive pain control alternative. However, the controversy over NSAIDs' effects on bone healing-stemming from their Cyclooxygenase-2 inhibition and associated risks of fracture non-union or delayed union-necessitates further investigation. Despite a comprehensive literature search, the study finds a lack of specific research on NSAIDs in postoperative hand fracture management, highlighting an urgent need for future studies to balance their benefits against possible risks.

Lack of Nuclear Localization of the Creb3l1 Transcription Factor Causes Defects in Caudal Fin Bifurcation in Zebrafish Danio rerio.

INTRODUCTION: The formation of normal bone and bone healing requires the cAMP-responsive element binding protein 3-like-1 (Creb3l1) transmembrane transcription factor, as deletion of the murine CREB3L1 results in osteopenic animals with limited capacity to repair bone after a fracture. Creb3l1 undergoes regulated intramembrane proteolysis (RIP) to release the N-terminal transcription activating (TA) fragment that enters the nucleus and regulates the expression of target genes. METHODS: To expand our understanding of Creb3l1's role in skeletal development and skeletal patterning, we aimed to generate animals expressing only the TA fragment of Creb3l1 lacking the transmembrane domain and thereby not regulated through RIP. However, the CRISPR/Cas9-mediated genome editing in zebrafish Danio rerio caused a frameshift mutation that added 56 random amino acids at the C-terminus of the TA fragment (TA+), making it unable to enter the nucleus. Thus, TA+ does not regulate transcription, and the creb3l1TA+/TA+ fish do not mediate creb3l1-dependent transcription. RESULTS: We document that the creb3l1TA+/TA+ fish exhibit defects in the patterning of caudal fin lepidotrichia, with significantly distalized points of proximal bifurcation and decreased secondary bifurcations. Moreover, using the caudal fin amputation model, we show that creb3l1TA+/TA+ fish have decreased regeneration and that their regenerates replicate the distalization and bifurcation defects observed in intact fins of creb3l1TA+/TA+ animals. These defects correlate with altered expression of the shha and ptch2 components of the Sonic Hedgehog signaling pathway in creb3l1TA+/TA+ regenerates. CONCLUSION: Together, our results uncover a previously unknown intersection between Creb3l1 and the Sonic Hedgehog pathway and document a novel role of Creb3l1 in tissue patterning.

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

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

Equal rates of bone healing and reduced surgical time with iliac crest allograft compared to autograft in medial opening wedge high tibial osteotomy: a randomized controlled clinical trial.

INTRODUCTION: Iliac crest autograft is frequently used to fill in bone defects after osteotomies. Nonetheless, surgery for bone autograft procurement is associated with morbidity and pain at the donor site. Alternatives to it have been explored, but there is no consensus to guide their application as a routine practice in several orthopedic procedures. Thus, this study was designed to compare the efficacy and safety between iliac crest autograft and allograft in medial opening wedge high tibial osteotomy. MATERIALS AND METHODS: Forty-seven patients with a symptomatic unilateral genu varum and an indication for high tibial osteotomy were randomly assigned to receive either autograft or allograft to fill the osteotomy site. Operative time, bone healing, and complication rates (delayed union, nonunion, superficial and deep infection, loss of correction, and hardware failure) were recorded after a one-year follow-up. Data were expressed as Mean ± Standard Deviation and considered statistically significant when p < 0.05. RESULTS: The time to radiologic union was similar between both groups (Allograft: 2.38 ± 0.97 months vs. Autograft: 2.45 ± 0.91 months; p = 0.79). Complication rates were also similar in both groups, with one infection in the allograft group and two in the autograft group, two delayed unions in the allograft group, and three in the autograft group. The operative time differed by 11 min between the groups, being lower in the allograft group (Allograft: 65.4 ± 15.1 min vs. Autograft: 76.3 ± 15.2 min; p = 0.02). CONCLUSION: Iliac crest allografts can be safely and effectively used in medial opening wedge high tibial osteotomy as it promotes the same rates of bone union as those achieved by autologous grafts, with the benefits of a shorter operative time. TRIAL REGISTRATION NUMBER: U1111-1280-0637 1 December 2022, retrospectively registered.

Titanium versus plasma electrolytic oxidation surface-modified magnesium miniplates in a forehead secondary fracture healing model in sheep.

Magnesium as a biodegradable material offers promising results in recent studies of different maxillo-facial fracture models. To overcome adverse effects caused by the fast corrosion of pure magnesium in fluid surroundings, various alloys, and surface modifications are tested in animal models. In specified cases, magnesium screws already appeared for clinical use in maxillofacial surgery. The present study aims to compare the bone healing outcome in a non-load-bearing fracture scenario of the forehead in sheep when fixed with standard-sized WE43 magnesium fixation plates and screws with plasma electrolytic oxidation (PEO) surface modification in contrast to titanium osteosynthesis. Surgery was performed on 24 merino mix sheep. The plates and screws were explanted en-bloc with the surrounding tissue after four and twelve weeks. The outcome of bone healing was investigated with micro-computed tomography, histological, immunohistological, and fluorescence analysis. There was no significant difference between groups concerning the bone volume, bone volume/ total volume, and newly formed bone in volumetric and histological analysis at both times of investigation. The fluorescence analysis revealed a significantly lower signal in the magnesium group after one week, although there was no difference in the number of osteoclasts per mm2. The magnesium group had significantly fewer vessels per mm2 in the healing tissue. In conclusion, the non-inferiority of WE43-based magnesium implants with PEO surface modification was verified concerning fracture healing under non-load-bearing conditions in a defect model. STATEMENT OF SIGNIFICANCE: Titanium implants, the current gold standard of fracture fixation, can lead to adverse effects linked to the implant material and often require surgical removal. Therefore, degradable metals like the magnesium alloy WE43 with plasma electrolytic oxidation (PEO) surface modification gained interest. Yet, miniplates of this alloy with PEO surface modification have not been examined in a fracture defect model of the facial skeleton in a large animal model. This study shows, for the first time, the non-inferiority of magnesium miniplates compared to titanium miniplates. In radiological and histological analysis, bone healing was undisturbed. Magnesium miniplates can reduce the number of interventions for implant removal, thus reducing the risk for the patient and minimizing the costs.

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

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

Mussel inspired 3D elastomer enabled rapid calvarial bone regeneration through recruiting more osteoprogenitors from the dura mater.

Currently, the successful healing of critical-sized calvarial bone defects remains a considerable challenge. The immune response plays a key role in regulating bone regeneration after material grafting. Previous studies mainly focused on the relationship between macrophages and bone marrow mesenchymal stem cells (BMSCs), while dural cells were recently found to play a vital role in the calvarial bone healing. In this study, a series of 3D elastomers with different proportions of polycaprolactone (PCL) and poly(glycerol sebacate) (PGS) were fabricated, which were further supplemented with polydopamine (PDA) coating. The physicochemical properties of the PCL/PGS and PCL/PGS/PDA grafts were measured, and then they were implanted as filling materials for 8 mm calvarial bone defects. The results showed that a matched and effective PDA interface formed on a well-proportioned elastomer, which effectively modulated the polarization of M2 macrophages and promoted the recruitment of dural cells to achieve full-thickness bone repair through both intramembranous and endochondral ossification. Single-cell RNA sequencing analysis revealed the predominance of dural cells during bone healing and their close relationship with macrophages. The findings illustrated that the crosstalk between dural cells and macrophages determined the vertical full-thickness bone repair for the first time, which may be the new target for designing bone grafts for calvarial bone healing.

Exploring Ascorbic Acid's Role in Orthopedic Practices: Present Theories, Innovative Approaches, and Prospects.

In the human body, ascorbic acid (AA) is known for its potent antioxidant and reducing properties and also plays a vital role in supporting the growth of bones and cartilage. It has been used extensively in orthopedic surgery. Ongoing studies under the umbrella of ascorbic acid research investigate its impact on bone and tendon physiology, as well as its influence on joint replacement and postoperative pain. The majority of both laboratory and human studies link the usage of ascorbic acid to enhanced bone health and improved tendon healing. Recent literature suggest that ascorbic acid administration may have a positive impact on the outcome of orthopedic procedures. On the other hand, controversy exists regarding the efficacy of ascorbic acid in reducing the incidence of complex regional pain syndrome. In brief, the effectiveness of ascorbic acid in enhancing orthopedic procedure outcomes remains a subject of ongoing investigation. Although certain studies have hinted at the potential positive influence of ascorbic acid on these outcomes, further research is required to validate its effectiveness and ascertain the ideal dosage and method of administration for maximizing its anticipated advantages. To establish the efficacy of ascorbic acid in improving orthopedic procedure outcomes, rigorous human trials of high quality are imperative. The aim of this review was to provide an overview of ascorbic acid's utilization in orthopedic practices and to pinpoint prospective areas for future research.

The use of hyperbaric oxygen for avascular necrosis of the femoral head and femoral condyle: a single centre's experience over 30 years.

Introduction: Avascular necrosis (AVN) is a rare progressive degenerative disease leading to bone and joint destruction. Patients often require surgical intervention. Femoral AVN is the most common anatomical location. Hyperbaric oxygen treatment (HBOT) has been shown to be effective in AVN. We present data collected from one centre over a 30-year period and compare the results with other published data. Methods: A retrospective chart review of all patients receiving HBOT for AVN at Fremantle and Fiona Stanley Hospitals since 1989 was performed. The primary outcome was radiological appearance using the Steinberg score, with secondary outcomes being subjective improvement, the need for joint replacement surgery and rates of complications. Results: Twenty-one joints in 14 patients (14 femoral heads and seven femoral condyles) were treated with HBOT since 1989. Two patients were excluded. Within the femoral head group, nine of the 14 joints (64%) had stable or improved magnetic resonance imaging (MRI) scans post treatment and at six months (minimum); 10 joints (71%) had good outcomes subjectively, three joints required surgical intervention, and three patients developed mild aural barotrauma. Within the femoral condyle group, all five joints had stable or improved post-treatment MRI scans (four had visible improvement in oedema and/or chondral stability), four joints reported good outcomes subjectively, none of the patients required surgical intervention (follow-up > six months). Conclusions: This single centre retrospective study observed prevention of disease progression in femoral AVN with the use of HBOT, comparable to other published studies. This adds to the body of evidence that HBOT may have a significant role in the treatment of femoral AVN.

How to explain the beneficial effects of leukocyte- and platelet-rich fibrin.

The survival of an organism relies on its ability to repair the damage caused by trauma, toxic agents, and inflammation. This process involving cell proliferation and differentiation is driven by several growth factors and is critically dependent on the organization of the extracellular matrix. Since autologous platelet concentrates (APCs) are fibrin matrices in which cells, growth factors, and cytokines are trapped and delivered over time, they are able to influence that response at different levels. The present review thoroughly describes the molecular components present in one of these APCs, leukocyte- and platelet-rich fibrin (L-PRF), and summarizes the level of evidence regarding the influence of L-PRF on anti-inflammatory reactions, analgesia, hemostasis, antimicrobial capacity, and its biological mechanisms on bone/soft tissue regeneration.