Chestnut-Inspired Hollow Hydroxyapatite 3D Printing Scaffolds Accelerate Bone Regeneration by Recruiting Calcium Ions and Regulating Inflammation.

This study aims to overcome the drawbacks associated with hydroxyapatite (HAP) dense structures after sintering, which often result in undesirable features such as large grain size, reduced porosity, high crystallinity, and low specific surface area. These characteristics hinder osseointegration and limit the clinical applicability of the material. To address these issues, a new method involving the preparation of hollow hydroxyapatite (hHAP) microspheres has been proposed. These microspheres exhibit distinctive traits including weak crystallization, high specific surface area, and increased porosity. The weak crystallization aligns more closely with early mineralization products found in the human body and animals. Moreover, the microspheres' high specific surface area and porosity offer advantages for protein loading and facilitating osteoblast attachment. This innovative approach not only mitigates the limitations of conventional HAP structures but also holds the potential for improving the effectiveness of hydroxyapatite in biomedical applications, particularly in enhancing osseointegration. Three-dimensional printed hHAP/chitosan (CS) scaffolds with different hHAP concentration gradients were manufactured, and the physical and biological properties of each group were systematically evaluated. In vitro and in vivo experiments show that the hHAP/CS scaffold has excellent performance in bone remodeling. Furthermore, in-scaffold components, hHAP and CS were cocultured with bone marrow mesenchymal stem cells to explore the regulatory role of hHAP and CS in the process of bone healing and to reveal the cell-level specific regulatory network activated by hHAP. Enrichment analysis showed that hHAP can promote bone regeneration and reconstruction by recruiting calcium ions and regulating inflammatory reactions.

Finite element study on three osteotomy methods for treating thoracolumbar osteoporotic fracture vertebral collapse complicated with neurological dysfunction.

BACKGROUND: Surgical methods for patients with osteoporotic fracture vertebral collapse complicated with neurological dysfunction are still a topic of debate. We designed an improved osteotomy for the treatment of osteoporotic compression fracture patients with neurological dysfunction. Compared with traditional osteotomy methods such as pedicle subtraction osteotomy (PSO) and bone-disc-bone osteotomy (BDBO), the osteotomy range is reduced. Therefore, we use a finite element method to analyze the biomechanical conditions of these three osteotomy methods and provide a mechanical theoretical basis for the surgical treatment of these three osteotomy methods. METHODS: Based on the CT scan of a patient with L1 osteoporotic fracture vertebral collapse and neurological dysfunction, the finite element model was constructed by importing Mimics software, and three different osteotomy models were established. The forces and displacements of internal fixation device, T1-L5 whole segment, T10 vertebral body, and T10/11 intervertebral disc were recorded under different working conditions. RESULTS: The displacement levels of internal fixation device, T1-L5 spine, T10 vertebral body, and T10/11 intervertebral disc in the modified osteotomy group were between BDBO group and PSO group. The stress in BDBO group was concentrated in titanium mesh and its maximum stress was much higher than that in PSO group and modified osteotomy group. The mechanical distribution of T10/11 intervertebral disc showed that the maximum stress distribution of the three osteotomy methods was similar. CONCLUSION: The relatively simple modified osteotomy has certain advantages in stress and displacement. In contrast, the stability of BDBO group was poor, especially in the lumbar intervertebral disc and lumbar body. For this type of osteotomy patients, it is recommended to avoid postoperative flexion so as not to increase the load.

pH-Responsive nanoplatform synergistic gas/photothermal therapy to eliminate biofilms in poly(L-lactic acid) scaffolds.

To date, implant-associated infection is still a significant clinical challenge, which cannot be effectively eliminated by single therapies due to the formation of microbial biofilms. Herein, a pH-responsive nanoplatform was constructed via the in situ growth of zinc sulfide (ZnS) nanoparticles on the surface of Ti3C2 MXene nanosheets, which was subsequently introduced in poly(L-lactic acid) (PLLA) to prepare a composite bone scaffold via selective laser sintering technology. In the acidic biofilm microenvironment, the degradation of ZnS released hydrogen sulfide (H2S) gas to eliminate the biofilm extracellular DNA (eDNA), thus destroying the compactness of the biofilm. Then, the bacterial biofilm became sensitive to hyperthermia, which could be further destroyed under near-infrared light irradiation due to the excellent photothermal property of MXene, finally achieving gas/photothermal synergistic antibiofilm and efficient sterilization. The results showed that the synergistic gas/photothermal therapy for the composite scaffold not only evidently inhibited the formation of biofilms, but also effectively eradicated the eDNA of the already-formed biofilms and killed 90.4% of E. coli and 84.2% of S. aureus under near infrared light irradiation compared with single gas or photothermal therapy. In addition, the composite scaffold promoted the proliferation and osteogenic differentiation of mouse bone marrow mesenchymal stem cells. Thus, the designed scaffold with excellent biofilm elimination and osteogenesis ability has great potential as an alternative treatment for implant-associated bone infections.

Osteoblast-derived exosomes promote osteogenic differentiation of osteosarcoma cells via URG4/Wnt signaling pathway.

Osteosarcoma is a primary malignant bone tumor. Although surgery and chemotherapy are the main treatment methods, the overall curative effect remains unsatisfactory. Therefore, there is an urgent need to develop new therapeutic options for osteosarcoma. In this study, the effect and molecular mechanism of osteoblast-derived exosomes on the treatment of osteosarcoma were evaluated. Human primary osteoblasts were cultured to observe the effects of osteoblast-derived exosomes on the osteogenic differentiation of osteosarcoma cells both in vitro and in vivo. Alizarin red staining and alkaline phosphatase detection were used to evaluate the degree of osteogenic differentiation, and immunofluorescence and Western blotting were used to detect protein expression. The results showed that osteoblast-derived exosomes effectively inhibited the proliferation of osteosarcoma cells and promoted their mineralization in vitro. The exosomes also significantly inhibited tumor growth and promoted tumor tissue mineralization in vivo. Osteoblast-derived exosomes upregulated the expression of bone sialoprotein, osteonectin, osteopontin, runt-related transcription factor 2, and Wnt inhibitory factor 1, downregulated the expression of cyclin D1, and suppressed the nuclear accumulation of ß-catenin and promoted its phosphorylation in vitro and in vivo. However, these effects were significantly reversed by upregulated gene (URG) 4 overexpression. These findings suggest that osteoblast-derived exosomes could activate the osteogenic differentiation process in osteosarcoma cells and promote their differentiation by targeting the URG4/Wnt signaling pathway.

Mini-Review: Tendon-Exposed Wound Treatments.

BACKGROUND: Tendon-exposed wounds are complex injuries with challenging reconstructions and no unified treatment mode. Furthermore, insufficient tissue volume and blood circulation disorders affect healing, which increases pain for the patient and affects their families and caretakers. REVIEW: As modern medicine advances, considerable progress has been made in understanding and treating tendon-exposed wounds, and current research encompasses both macro-and micro-studies. Additionally, new treatment methods have emerged alongside the classic surgical methods, such as new dressing therapies, vacuum sealing drainage combination therapy, platelet-rich plasma therapy, and live-cell bioengineering. CONCLUSIONS: This review summarizes the latest treatment methods for tendon-exposed wounds to provide ideas and improve their treatment.

Modified posterior osteotomy for osteoporotic vertebral collapse with neurological dysfunction in thoracolumbar spine: a preliminary study.

OBJECTIVE: The risk of osteoporotic vertebral collapse (OVC) associated with delayed neurological dysfunction (DND) is substantial, and performing surgery for this condition in elderly patients presents challenges. The focus of the current research is on simplifying surgical procedures while maintaining their effectiveness. This study was designed to contribute clinical data supporting the use of modified posterior osteotomy for treating thoracolumbar OVC with DND. The study compares perioperative clinical parameters, imaging data characteristics, and changes in efficacy outcome indicators to provide evidence for the advancement of this technique. METHODS: A total of 12 patients diagnosed with osteoporotic vertebral collapse and neurological dysfunction were included in the study. All patients underwent modified posterior osteotomy. Data regarding perioperative and radiological parameters as well as complications such as surgery duration, blood loss, ASIA grade, VAS, ODI, regional kyphosis angle (RKA), anterior vertebral height ratio (AVHr), and spinal canal clearance ratio (SCCr), were collected retrospectively. These parameters were then analysed to evaluate the clinical efficacy and safety of the modified posterior osteotomy technique. RESULTS: A total of 12 patients were included in the study, with a mean age of 65.5 ± 9.7 years. The average follow-up period was 29.4 ± 5.0 months. The mean operative blood loss was 483.3 ± 142.0 ml, and the average operative time was 3.7 ± 0.7 h. The visual analogue scale (VAS) score decreased from a preoperative value of 5.8 ± 0.7 to a final follow-up value of 1.3 ± 0.8 (P < 0.05), indicating a significant improvement in pain. The ODI decreased from 65.2 ± 6.0 before surgery to 20.5 ± 7.0, indicating a decrease in disability, and the postoperative neurological function showed a significant improvement. Correction of the RKA was observed, with the angle changing from 35.8 ± 10.8° before surgery to 20.0 ± 3.5° after surgery and to 22.5 ± 3.1° at the final follow-up. Similarly, correction of the AVHr was observed, with the height changing from 39.3 ± 18.0 to 63.0 ± 14.3 after surgery and to 53.9 ± 8.9 at the final follow-up. Correction of the SCCr was also observed, with the ratio changing from 54.9 ± 5.4 to 68.1 ± 5.3 after surgery and to 68.68 ± 6.76 at the final follow-up. CONCLUSIONS: Posterior modified osteotomy is an effective treatment for thoracolumbar osteoporotic fractures with OVC combined with DND. It can significantly preserve vertebral height, increase vertebral canal volume, correct kyphotic angle, and improve postoperative neurological function. The simplified osteotomy also offers advantages in terms of operating time, blood loss, postoperative VAS score, and improvement in lumbar function.

Hollow Hydroxyapatite Microspheres Loaded with rhCXCL13 to Recruit BMSC for Osteogenesis and Synergetic Angiogenesis to Promote Bone Regeneration in Bone Defects.

Introduction: Bone tissue engineering is a promising method to treat bone defects. However, the current methods of preparing composite materials that mimic the complex structure and biological activity of natural bone are challenging for recruitment of bone marrow mesenchymal stem cells (BMSCs), which affects the application of these materials in situ bone regeneration. Hollow hydroxyapatite microspheres (HHMs) possess a natural porous bone structure, good adsorption, and slow release of chemokines, but have low ability to recruit BMSCs and induce osteogenesis. In this study, The HHM/chitosan (CS) and recombinant human C-X-C motif chemokine ligand 13 (rhCXCL13)-HHM/CS biomimetic scaffolds that optimize bone regeneration and investigated their mechanism of BMSC recruitment and osteogenesis through cell and animal experiments and transcriptomic sequencing. Methods: Evaluate the physical characteristics of the HHM/CS and rhCXCL13-HHM/CS biomimetic scaffolds through Scanning Electron Microscopy (SEM), X-Ray Diffraction (XRD), and the cumulative release curve of rhCXCL13. Transwell migration experiments and co-culture with BMSCs were conducted to study the recruitment ability and osteogenic differentiation of the scaffolds. Transcriptomic sequencing was performed to analyze the osteogenic differentiation mechanism. The osteogenesis and bone healing performance were evaluated using a rabbit radial defect model. Results: SEM demonstrated that the rhCXCL13-HHM/CS scaffold comprised hydroxyapatite microspheres in a porous three-dimensional network. The rhCXCL13 showed excellent sustained release capability. The rhCXCL13-HHM/CS scaffold could recruit BMSCs and induce bone regeneration. Transcriptome sequencing and experimental results showed that the osteogenesis mechanism of rhCXCL13-HHM/CS was through the PI3K-AKT pathway. In vivo, the rhCXCL13-HHM/CS scaffold significantly promoted osteogenesis and angiogenesis at 12 weeks after surgery. Conclusion: The rhCXCL13-HHM/CS scaffold demonstrates excellent potential for BMSC recruitment, osteogenesis, vascularized tissue-engineered bone reconstruction, and drug delivery, providing a theoretical basis for material osteogenesis mechanism study and promising clinical applications for treating large bone defects.

Study on the influence of scaffold morphology and structure on osteogenic performance.

The number of patients with bone defects caused by various bone diseases is increasing yearly in the aging population, and people are paying increasing attention to bone tissue engineering research. Currently, the application of bone tissue engineering mainly focuses on promoting fracture healing by carrying cytokines. However, cytokines implanted into the body easily cause an immune response, and the cost is high; therefore, the clinical treatment effect is not outstanding. In recent years, some scholars have proposed the concept of tissue-induced biomaterials that can induce bone regeneration through a scaffold structure without adding cytokines. By optimizing the scaffold structure, the performance of tissue-engineered bone scaffolds is improved and the osteogenesis effect is promoted, which provides ideas for the design and improvement of tissue-engineered bones in the future. In this study, the current understanding of the bone tissue structure is summarized through the discussion of current bone tissue engineering, and the current research on micro-nano bionic structure scaffolds and their osteogenesis mechanism is analyzed and discussed.

Solitary bone plasmacytoma of the tibia presenting as chronic osteomyelitis: A rare case report and literature review.

RATIONALE: Plasmacytoma is a rare plasma cell dyscrasia that grows within the axial skeleton or soft tissue structures as solitary or multiple masses. The primary types are solitary plasmacytoma, including solitary bone plasmacytoma (SBP) and solitary extramedullary plasmacytoma, and multiple solitary plasmacytomas. SBP is characterized by localized proliferation of monoclonal plasma cells and is rare. However, SBP with chronic osteomyelitis is even rarer. PATIENT CONCERNS: A 47-year-old man previously diagnosed with chronic osteomyelitis presented with repeated discharge and ulceration in the front of his right tibia. DIAGNOSIS, INTERVENTIONS AND OUTCOMES: Lower extremity magnetic resonance imaging (MRI) and computed tomography (CT) examinations showed dead bone formation and surrounding inflammatory edema. Thus, the patient underwent dead bone excision and fenestration of the bone marrow cavity. The histopathologic examination results indicated plasmacytoma. Therefore, we administered radiotherapy with satisfactory results. LESSONS: Physicians should pay close attention to chronic osteomyelitis because it may be accompanied by plasmacytoma. Postoperative pathological and immunohistochemical examinations are crucial, and surgical resection of the lesion and local radiotherapy are effective treatment methods.

The efficacy and safety of platelet-rich plasma in the tendon-exposed wounds: a preliminary study.

OBJECTIVE: Currently, among wounds with large skin tissue defects caused by various reasons, the treatment of refractory wounds is still a major clinical problem. This study is aimed to preliminarily assess the therapeutic potentials of platelet-rich plasma (PRP) in refractory wounds with exposed tendons, as well as corresponding efficacy and safety. METHODS: A total of 12 patients (5 males and 7 females) with refractory wounds and exposed tendons who were admitted to our hospital from June 2018 to December 2020 were included in this study. After the preparation of PRP, the included patients underwent the PRP injection after the debridement of wounds, and the efficacy and prognosis were assessed by the same group of senior surgeons. RESULTS: The average age of included patients was 42.7 ± 12.9 years, and the causes of injury included traffic accidents (3 cases), contusion (2 cases), burns (2 cases), diabetes complications (4 cases), and melanoma complications (1 cases). The average healing time was 23.0 ± 5.0 days, and the mean size of the wound was 3.1 × 5.1 cm2. During the whole treatment process, Vancouver Scar Scale (VSS) decreased from 7.4 ± 1.6 before PRP treatment to 3.6 ± 0.9 after treatment (P < 0.001), Manchester Scar Scale (MSS) decreased from 12.3 ± 4.5 before PRP treatment to 5.4 ± 1.2 after treatment (P < 0.001), and no redness and swelling were observed around wounds, the size and degree of wounds gradually reduced, the coverage rate of granulation tissue was acceptable, overall quality of scar was relatively good, skin sensitivity around wounds was normal, there was no local wounds secretion, and postoperative patient's satisfaction was relatively good during follow-up. CONCLUSIONS: Our study has preliminarily indicated that PRP can promote the wounds healing, reduce the inflammation around wounds, and improve the granulation tissue and angiogenesis, thereby effectively polishing up the safety and efficacy.

Clinical application of multiple 3D-printed guide plates for precise reduction and fixation of comminuted patellar fractures.

Because of the lack of anatomical landmarks during reduction of multiple articular surfaces and fragments in comminuted patellar fractures, loss of bone fragments or aggravation of soft tissue and ligament injuries readily occurs. In the present case, we used multiple three-dimensional (3D)-printed guide plates to reduce and fix a comminuted patellar fracture. A 22-year-old man was hospitalized for 2 days because of left knee joint pain and limited movement caused by a traffic accident. Preoperative imaging revealed a comminuted fracture of the left patella (type 34-C3 according to the AO/OTA classification). Throughout a 2-year follow-up, the patient remained in generally good condition with no significant limitation of his left knee joint activity. Application of multiple 3D-printed guide plates is a safe and effective auxiliary technique for the treatment of comminuted patellar fractures. This novel technique can shorten the operation time, reduce the number of fluoroscopic procedures, and ensure fracture healing and recovery of knee joint function through reliable reduction of the articular surface.

Circ_0000285 regulates proliferation, migration, invasion and apoptosis of osteosarcoma by miR-409-3p/IGFBP3 axis.

BACKGROUND: Circular RNAs (circRNAs) are important regulators in the pathogenesis of diseases and affects the occurrence and development of diseases. However, the role of circRNAs in osteosarcoma (OS) has not been fully elucidated. METHODS: The expression of circ_0000285, miR-409-3p and insulin-like growth factor binding protein 3 (IGFBP3) was detected using quantitative real-time PCR (qRT-PCR). The protein level of IGFBP3 was measured using western blot. CCK-8 and colony formation assays were used to determine cell proliferation. Flow cytometry was applied to measure cell cycle and cell apoptosis. Transwell assay was used to assess cell invasion and migration. Dual-luciferase reporter assay and RNA Binding Protein Immunoprecipitation (RIP) assay were performed to determine the relationship among circ_0000285, miR-409-3p and IGFBP3. The animal experiments were performed to determine the function of circ_0000285 in vivo. RESULTS: In this study, we found that the expression of circ_0000285 was significantly increased in OS tissues and cells and was enriched in the cytoplasm. Knockdown of circ_0000285 inhibited OS growth in vitro and in vivo. Moreover, miR-409-3p was a target miRNA of circ_0000285 and miR-409-3p targets to IGFBP3 in OS. Besides, circ_0000285 could promote proliferation, migration, invasion and inhibit apoptosis of osteosarcoma by miR-409-3p/IGFBP3 axis. CONCLUSION: In this study, circ_0000285 regulated proliferation, migration, invasion and apoptosis of OS cells by miR-409-3p/IGFBP3 axis, implying that circ_0000285 was a potential target for OS therapy.

Study of PLGA microspheres loaded with pOsx/PEI nanoparticles for repairing bone defects in vivo and in vitro.

BACKGROUND: Autogenous or allogenic bone transplantation is the main treatment for bone defects and nonunions. However, the shortcomings of autogenous or allogenic bone transplantation limit its wide application in clinical use. OBJECTIVES: This study investigated the effect of poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with pOsterix (pOsx)/polyethylenimine (PEI) nanoparticles in repairing bone defects and explored its mechanism. MATERIAL AND METHODS: Poly(lactic-co-glycolic acid) microspheres loaded with pOsx/PEI nanoparticles were constructed. The Osx transfection effect was detected by fluorescence quantitative PCR and western blotting methods. 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-diphenytetrazoliumromide (MTT) and flow cytometry methods were used to detect cell proliferation. The collagen I (Col-1), osteopontin (OPN) and osteocalcin (OC) expression levels were detected using real-time polymerase chain reaction (RT-PCR) and western blotting methods. Bone defect model was constructed. Bone repair was detected using X-ray, hematoxylin and eosin (H&E) staining, and Mason staining methods. RESULTS: PLGA@pOsx/PEI has transfection effect both in vitro and in vivo, does not affect cell proliferation and is safe for cells. PLGA@pOsx/PEI could promote the expression of Col-1, OPN and OC in vitro and in vivo. PLGA@pOsx/PEI could promote osteogenesis in vivo. CONCLUSIONS: PLGA@pOsx/PEI with high Osx expression could promote the expression of OC, OPN, and COL-I. PLGA@pOsx/PEI can be used as a material for repairing bone defects and can promote bone formation. These results provide a theoretical and practical basis for its further clinical application.

Study of bone repair mediated by recombination BMP-2/ recombination CXC chemokine Ligand-13-loaded hollow hydroxyapatite microspheres/chitosan composite.

AIMS: The present study aimed to investigate the mechanism of bone repair mediated by recombination BMP-2 (rhBMP-2)/recombination CXC chemokine ligand-13 (rhCXCL13)-loaded hollow hydroxyapatite (HA) microspheres/chitosan (CS) composite. MATERIALS AND METHODS: Firstly, the biological activity of rhBMP-2 and rhCXCL13 released from the complex was investigated. Secondly, the effect of rhBMP-2 sustained release solution on ALP activity and rhCXCL13 sustained release solution on cell migration of rat bone marrow mesenchyme stem cells was tested. Thirdly, osteoblasts differentiation test, X-ray scoring and three-point bending test were performed. Finally, the mRNAs expression of osteogenic marker genes and the protein expression of Runx2 was tested by reverse transcription-polymerase chain reaction (RT-PCR) and western blotting (WB), respectively. KEY FINDINGS: RhBMP-2 could significantly promote the proliferation and differentiation, and RhCXCL13 could promote the migration of rat bone marrow MSCs. Detection of ALP activity and calcium salt deposition showed that rhBMP-2 and rhCXCL13 could significantly improve the biological activity and promote cell differentiation ability. X-ray scoring of radius and flexural strength test showed that rhBMP-2 and rhCXCL13 could promote bone healing and improve the bending resistance of bone tissue. The in vitro molecular experiments including RT-PCR and WB further demonstrated the roles of rhBMP-2 and rhCXCL13 in bone formation and bone repair. SIGNIFICANCE: Our results indicated that the hollow HA microspheres/CS composite could be effective as a delivery vehicle for rhBMP-2 and rhCXCL13 in bone regeneration and bone repair. In this process, rhBMP-2 may promote bone regeneration by regulating bone marrow MSCs cells recruited by rhCXCL13.