Advances in natural and synthetic macromolecules with stem cells and extracellular vesicles for orthopedic disease treatment.

Serious orthopedic disorders resulting from myriad diseases and impairments continue to pose a considerable challenge to contemporary clinical care. Owing to its limited regenerative capacity, achieving complete bone tissue regeneration and complete functional restoration has proven challenging with existing treatments. By virtue of cellular regenerative and paracrine pathways, stem cells are extensively utilized in the restoration and regeneration of bone tissue; however, low survival and retention after transplantation severely limit their therapeutic effect. Meanwhile, biomolecule materials provide a delivery platform that improves stem cell survival, increases retention, and enhances therapeutic efficacy. In this review, we present the basic concepts of stem cells and extracellular vesicles from different sources, emphasizing the importance of using appropriate expansion methods and modification strategies. We then review different types of biomolecule materials, focusing on their design strategies. Moreover, we summarize several forms of biomaterial preparation and application strategies as well as current research on biomacromolecule materials loaded with stem cells and extracellular vesicles. Finally, we present the challenges currently impeding their clinical application for the treatment of orthopedic diseases. The article aims to provide researchers with new insights for subsequent investigations.

Multifunctional hyaluronic acid/gelatin methacryloyl core-shell microneedle for comprehensively treating oral mucosal ulcers.

Oral ulceration is the most common oral mucosal disease. Oral mucosal ulcers are extremely painful, may interfere with eating and speaking, and potentially complicate systemic symptoms in severe cases. The humid and highly dynamic environment of the oral cavity makes local drug administration for treating oral mucosal ulcers challenging. To overcome these challenges, we designed and prepared a novel dissolving microneedle (MN) patch containing multiple drugs in a core-shell to promote oral ulcer healing. The MNs contained a methacrylate gelatin shell layer of basic fibroblast growth factor (bFGF), a hyaluronic acid (HA) core loaded with dexamethasone (DXMS), and zeolite imidazoline framework-8 (ZIF-8) encapsulated in the HA-based backplane. Progressive degradation of gelatin methacryloyl (GelMA) from the tip of the MN patch in the oral mucosa resulted in sustained bFGF release at the lesion site, significantly promoting cell migration, proliferation, and angiogenesis. Moreover, the rapid release of HA and, subsequently, DXMS inhibited inflammation, and the remaining MN backing after the tip dissolved behaved as a dressing, releasing ZIF-8 for its antimicrobial effects. This novel, multifunctional, transmucosal core-shell MN patch exhibited excellent anti-inflammatory, antimicrobial, and pro-healing effects in vivo and in vitro, suggesting that it can promote oral ulcer healing.

Antibacterial microneedle patch releases oxygen to enhance diabetic wound healing.

Cell growth and metabolism require an adequate supply of oxygen. However, obtaining sufficient oxygen from the blood circulating around diabetic wounds is challenging. Nevertheless, achieving a continuous and stable oxygen supply is required for these wounds to heal. Hence, in this study, we report a novel antibacterial oxygen-producing silk fibroin methacryloyl hydrogel microneedle (MN) patch comprising tips encapsulated with calcium peroxide and catalase and a base coated with antibacterial Ag nanoparticles (AgNPs). The tip of the MN patch continuously releases oxygen and inhibits the production of reactive oxygen species. This accelerates diabetic wound healing by promoting cellular accretion and migration, macrophage M2 polarization, and angiogenesis. The AgNPs at the base of the MN patch effectively combat microbial infection, further facilitating wound repair. These findings suggest that using this multifunctional oxygen-producing MN patch may be a promising strategy for diabetic wound healing in clinical settings.

Construction of intelligent drug delivery system based on polysaccharide-derived polymer micelles: A review.

Micelles are nanostructures developed via the spontaneous assembly of amphiphilic polymers in aqueous systems, which possess the advantages of high drug stability or active-ingredient solubilization, targeted transport, controlled release, high bioactivity, and stability. Polysaccharides have excellent water solubility, biocompatibility, and degradability, and can be modified to achieve a hydrophobic core to encapsulate hydrophobic drugs, improve drug biocompatibility, and achieve regulated delivery of the loaded drug. Micelles drug delivery systems based on polysaccharides and their derivatives show great potential in the biomedical field. This review discusses the principles of self-assembly of amphiphilic polymers and the formation of micelles; the preparation of amphiphilic polysaccharides is described in detail, and an overview of common polysaccharides and their modifications is provided. We focus on the review of strategies for encapsulating drugs in polysaccharide-derived polymer micelles (PDPMs) and building intelligent drug delivery systems. This review provides new research directions that will help promote future research and development of PDPMs in the field of drug carriers.

Intraoperative pain prediction of percutaneous kyphoplasty under local anesthesia by preoperative experimental pain assessment.

BACKGROUND: Percutaneous kyphoplasty (PKP) is the preferred treatment for osteoporotic vertebral compression fractures (OVCF) Currently, the preoperative anesthesia methods for PKP are mainly local anesthesia and tracheal intubation general anesthesia. OBJECTIVE: To assess whether patient sensitivity to pain measured preoperatively could predict the patients' pain response during PKP treatment under local anesthesia, to facilitate the development of an optimal preoperative anesthesia plan for patients. METHODS: Fifty-five female patients diagnosed with osteoporotic single vertebral fracture who were treated with PKP under local anesthesia were selected. The patients' pain sensitivities, including pain threshold and pain tolerance threshold, were evaluated with a pain test device on the day before the operation in the ward. Heart rate (HR), mean arterial pressure (MAP), and blood oxygen saturation (SpO2) were recorded before anesthesia, post-anesthesia, after needle puncture, and after balloon dilatation. At the same time, blood was drawn at the above time points to determine the level of norepinephrine (NA) as an indicator of intraoperative pain stress response. The numerical rating scale (NRS) during surgery was recorded at the end of the surgery. RESULTS: The preoperative pain tolerance threshold of 55 surgical patients was correlated with the intraoperative NRS score (r=-0.768, P< 0.001), as well as with the preoperative and intraoperative changes in HR (r=-0.791, P< 0.001), MAP (r=-0.819, P< 0.001), and NA (r=-0.553, P< 0.001). Thus, the lower the preoperative pain tolerance threshold, the more severe the patient's response to pain during PKP treatment under local anesthesia, and the greater the hemodynamic changes. Consequently, the intraoperative experience becomes worse. However, there was no correlation between preoperative pain threshold and NRS scores (r=-0.069, P= 0.616) nor between the preoperative and intraoperative changes in HR (r= 0.103, P= 0.453), MAP (r= 0.086, P= 0.535), and NA (r=-0.058, P= 0.674). CONCLUSION: The results indicated that preoperative pain assessment could predict the level of pain response in OVCF patients during PKP surgery under local anesthesia.

3D printed scaffolds based on hyaluronic acid bioinks for tissue engineering: a review.

Hyaluronic acid (HA) is widely distributed in human connective tissue, and its unique biological and physicochemical properties and ability to facilitate biological structure repair make it a promising candidate for three-dimensional (3D) bioprinting in the field of tissue regeneration and biomedical engineering. Moreover, HA is an ideal raw material for bioinks in tissue engineering because of its histocompatibility, non-immunogenicity, biodegradability, anti-inflammatory properties, anti-angiogenic properties, and modifiability. Tissue engineering is a multidisciplinary field focusing on in vitro reconstructions of mammalian tissues, such as cartilage tissue engineering, neural tissue engineering, skin tissue engineering, and other areas that require further clinical applications. In this review, we first describe the modification methods, cross-linking methods, and bioprinting strategies for HA and its derivatives as bioinks and then critically discuss the strengths, shortcomings, and feasibility of each method. Subsequently, we reviewed the practical clinical applications and outcomes of HA bioink in 3D bioprinting. Finally, we describe the challenges and opportunities in the development of HA bioink to provide further research references and insights.

Hydrogel-based treatments for spinal cord injuries.

Spinal cord injury (SCI) is characterized by damage resulting in dysfunction of the spinal cord. Hydrogels are common biomaterials that play an important role in the treatment of SCI. Hydrogels are biocompatible, and some have electrical conductivity that are compatible with spinal cord tissues. Hydrogels have a high drug-carrying capacity, allowing them to be used for SCI treatment through the loading of various types of active substances, drugs, or cells. We first discuss the basic anatomy and physiology of the human spinal cord and briefly discuss SCI and its treatment. Then, we describe different treatment strategies for SCI. We further discuss the crosslinking methods and classification of hydrogels and detail hydrogel biomaterials prepared using different processing methods for the treatment of SCI. Finally, we analyze the future applications and limitations of hydrogels for SCI. The development of biomaterials opens up new possibilities and options for the treatment of SCI. Thus, our findings will inspire scholars in related fields and promote the development of hydrogel therapy for SCI.

Comparison of unipedicular and bipedicular kyphoplasty for treating acute osteoporotic vertebral compression fractures in the lower lumbar spine: a retrospective study.

BACKGROUND: Unipedicular and bipedicular approaches for percutaneous kyphoplasty are reportedly both effective in treating osteoporotic vertebral compression fractures (OVCFs). However, most studies have reported thoracolumbar fractures, with few reports describing the treatment of the lower lumbar spine. Here, we compared the clinical and radiological results of unipedicular and bipedicular approaches for percutaneous kyphoplasty for treating osteoporotic vertebral compression fractures. METHODS: We retrospectively reviewed the records of 160 patients who underwent percutaneous kyphoplasty for lower lumbar (L3-L5) osteoporotic vertebral compression fractures between January 2016 and January 2020. Patient characteristics, surgical outcomes, operation time, blood loss, clinical and radiological features, and complications were compared between two groups. Cement leakage, height restoration, and cement distribution were calculated from the radiographs. Visual pain analog scale (VAS) and Oswestry Disability Index (ODI) were calculated before surgery, immediately post-surgery, and 2 years after surgery. RESULTS: The mean age, sex, body mass index, injury time, segmental distribution, and morphological classification of fractures before surgery did not differ significantly between the groups. The results showed significant improvements in the VAS score, ODI score, and vertebral height restoration in each group (p < 0.05), with no significant differences between the two groups (p > 0.05). The mean operation time and extent of blood loss were lower in the unipedicular group than those in the bipedicular group (p < 0.05). Different types of bone cement leakage were observed in both groups. Leakage rate was higher in the bipedicular group than in the unipedicular group. Patients in the bipedicular group showed greater improvement in bone cement distribution than those in the unipedicular group (p < 0.05). CONCLUSIONS: The clinical and radiological results of unipedicular percutaneous kyphoplasty for treating osteoporotic vertebral compression fractures in the lower lumbar region were similar to those of bipedicular percutaneous kyphoplasty. However, the unipedicular approach resulted in shorter surgical time, less blood loss, and less bone cement leakage. Thus, the unipedicular approach may be preferable owing to its several advantages.

Sitagliptin attenuates neuronal apoptosis via inhibiting the endoplasmic reticulum stress after acute spinal cord injury.

Regulation of endoplasmic reticulum stress (ER) stress-induced apoptosis and nerve regeneration is a hopeful way for acute spinal cord injury (SCI). Sitagliptin (Sita) is one of dipeptidyl peptidase-4 (DPP-4) inhibitor, which is beneficial neurons damaged diseases. However, its protective mechanisms of avoiding nerve injury remain unclear. In this study, we further investigated the mechanism of the anti-apoptotic and neuroprotective effects of Sita in promoting locomotor recovery from SCI. In vivo results showed that Sita treatment reduced neural apoptosis caused by SCI. Moreover, Sita effectively attenuated the ER tress and associated apoptosis in rats with SCI. A striking feature was the occurrence of nerve fiber regeneration at the lesion site, which eventually led to significant locomotion recovery. In vitro results showed that the PC12 cell injury model induced by Thapsigargin (TG) also showed similar neuroprotective effects. Overall, sitagliptin showed potent neuroprotective effects by targeting the ER stress-induced apoptosis both in vivo and vitro, thus facilitating the regeneration of the injured spinal cord.

Percutaneous mesh-container-plasty versus percutaneous kyphoplasty for the treatment of Kümmell's disease: a retrospective cohort study.

BACKGROUND: Both percutaneous kyphoplasty (PKP) and percutaneous mesh-container-plasty (PMCP) were important procedures for the treatment of Kümmell's disease. This study aimed to compare the clinical and radiological results of PKP and PMCP for the treatment of Kümmell's disease. METHODS: This study included patients with Kümmell's disease treated at our center between January 2016 and December 2019. A total of 256 patients were divided into two groups according to the surgical treatment they received. Clinical, radiological, epidemiological, and surgical data were compared between the two groups. Cement leakage, height restoration, deformity correction, and distribution were evaluated. The visual analog scale (VAS), Oswestry Disability Index (ODI), and short-form 36 health survey domains "role-physical" (SF-36 rp) and "bodily pain" (SF-36 bp) were calculated preoperatively, immediately after surgery, and 1-year postoperatively. RESULTS: The VAS and ODI scores improved in the PKP [preoperative: 6 (6-7), 68.75 ± 6.64; postoperative: 2 (2-3), 23.25 ± 3.50, respectively] (p < 0.05) and the PMCP [preoperative: 6 (5-7), 67.70 ± 6.50; postoperative: 2 (2-2), 22.24 ± 3.55, respectively] groups (p < 0.05). There were significant differences between the two groups. The mean cost in the PKP group was lower than that in the PMCP group (3697 ± 461 vs. 5255 ± 262 USD, p < 0.05). The cement distribution in the PMCP group was significantly higher than that in the PKP group (41.81 ± 8.82% vs. 33.65 ± 9.24%, p < 0.001). Cement leakage was lower in the PMCP group (23/134) than in the PKP group (35/122) (p < 0.05). The anterior vertebral body height ratio (AVBHr) and Cobb's angle improved in the PKP (preoperative: 70.85 ± 16.62% and 17.29 ± 9.78°; postoperative: 80.28 ± 13.02% and 13.05 ± 8.40°, respectively) and PMCP (preoperative: 70.96 ± 18.01% and 17.01 ± 10.53°; postoperative: 84.81 ± 12.96% and 10.76 ± 9.23°, respectively) groups (p < 0.05). There were significant differences in vertebral body height recovery and segmental kyphosis improvement between the two groups. CONCLUSIONS: PMCP had advantages over PKP in terms of pain relief and functional recovery for the treatment of Kümmell's disease. Moreover, PMCP is more effective than PKP in preventing cement leakage, increasing cement distribution, and improving vertebral height and segmental kyphosis, despite its higher cost.

Percutaneous mesh-container-plasty versus percutaneous kyphoplasty in the treatment of malignant thoracolumbar compression fractures: a retrospective cohort study.

OBJECTIVE: This study aimed to compare the clinical and radiological results of percutaneous mesh-container-plasty versus percutaneous kyphoplasty in the treatment of malignant thoracolumbar compression fractures. METHODS: Patients with malignant thoracolumbar compression fractures treated in a single tertiary care center between January 2011 and December 2020 were retrospectively reviewed and included in the study. Ninety-four patients who were diagnosed by pathological biopsy were divided into 2 groups according to the type of surgical treatment: the percutaneous kyphoplasty group (50 patients: 24 male, 26 female; mean age=73.02 ± 7.79 years) and the percutaneous mesh-container-plasty group (44 patients: 21 male, 23 female; mean age=74.68 ± 7.88 years). The epidemiological data, surgical outcomes, and clinical and radiological features were compared between the 2 groups. Cement leakage, height restoration, deformity correction, and cement distribution were calculated from the radiographs. The visual analog scale, Oswestry disability index, Karnofsky performance scale scores, and short-form 36 health survey domains role physi cal and bodily pain were calculated preoperatively, immediately, and 1 year postoperatively. RESULTS: The visual analog scale score improved from 5 (range=4-6) preoperatively to 2 (range=2-3) immediately postoperatively in the percutaneous kyphoplasty group and from 5 (range=4-6) preoperatively to 2 (range=2-2) immediately postoperatively in the percutane ous mesh-container-plasty group; there was a significant difference between the 2 groups (P=.018). Although Oswestry disability index, Karnofsky performance scale, short-form 36 health survey domains bodily pain and role physical significantly improved in both groups after surgery compared to the preoperative period, there was no significant difference between the 2 groups (P > .05). The mean cost in the percutaneous kyphoplasty group was lower than that in the percutaneous mesh-container-plasty group (5563 ± 439 vs. 6569 ± 344 thousand dollars, P < .05). There was no difference between the cement volume in the 2 groups, and cement distribution in the percutaneous mesh-container-plasty group was higher than that in the percutaneous kyphoplasty group (44.30% ± 10.25% vs. 32.54% ± 11.76%, P < .05). Cement leakage was found to be lesser in the percutaneous mesh-container-plasty group (7/44) than in the percutane ous kyphoplasty group (18/50, P < .05). There were no statistically significant differences in the recovery of vertebral body height and improvement of segmental kyphosis between the 2 groups (P > .05). CONCLUSION: Percutaneous kyphoplasty and percutaneous mesh-container-plasty both have significant abilities in functional recovery, height restoration, and segment kyphosis improvement in treating malignant thoracolumbar compression fractures. Percutaneous mesh container-plasty may be better able to relieve pain, inhibit cement leakage, and improve cement distribution than percutaneous kypho plasty. However, percutaneous mesh-container-plasty requires a relatively longer procedure and is more expensive than percutaneous kyphoplasty. LEVEL OF EVIDENCE: Level III, Therapeutic Study.

Erratum: Bioactive antibacterial silica-based nanocomposites hydrogel scaffolds with high angiogenesis for promoting diabetic wound healing and skin repair: Erratum.

[This corrects the article DOI: 10.7150/thno.41839.].

Biochemical and functional characterization of an endonuclease III from Thermococcus barophilus Ch5.

Endonuclease III (EndoIII) is a bifunctional DNA glycosylase that is essential to excise thymine glycol (Tg) from DNA. Although EndoIII is widespread in bacteria, eukarya and Archaea, our understanding on archaeal EndoIII function remains relatively incomplete due to the limited reports. Herein, we characterized an EndoIII from the hyperthermophilic euryarchaeon Thermococcus barophilus Ch5 (Tba-EndoIII) biochemically, demonstrating that the enzyme can excise Tg from dsDNA and display maximum activity at 50 ~ 70 °C and at pH 6.0 ~ 9.0 without the requirement of a divalent metal ion. Importantly, Tba-EndoIII differs from other reported archaeal EndoIII homologues in thermostability and salt requirement. As observed in other EndoIII homologues, the conserved residues D155 and H157 in Helix-hairpin-Helix motif of Tba-EndoIII are essential for Tg excision. Intriguingly, we first dissected that the conserved residues C215 and C221 in the Fe-S cluster loop in Tba-EndoIII are involved in intermediate formation and Tg excision. Additionally, we first revealed that the conserved residue L48 is flexible for intermediate formation and AP cleavage, but plays no detectable role in Tg excision. Overall, our work has revealed additional archaeal EndoIII function and catalytic mechanism.

Effectiveness and safety of ultrasound-guided thoracic paravertebral block versus local anesthesia for percutaneous kyphoplasty in patients with osteoporotic compression fracture.

BACKGROUND: Kyphoplasty for osteoporotic vertebral compression fractures (OVCF) is a short but painful intervention. Different anesthetic techniques have been proposed to control pain during kyphoplasty; however, all have limitations. OBJECTIVE: To compare the effectiveness and safety of ultrasound-guided thoracic paravertebral block with local anesthesia for percutaneous kyphoplasty (PKP). METHODS: In this prospective study, non-randomized patients with OVCF undergoing PKP received either ultrasound-guided thoracic paravertebral block (group P) or local anesthesia (group L). Perioperative pain, satisfaction with anesthesia, and complications were compared between the groups. RESULTS: Mean intraoperative (T1-T4) perioperative visual analog scale (VAS) scores were significantly lower in group P than in group L (2 [1-3] vs. 3 [2-4], 2 [2-3] vs. 4 [2-4], 2 [2-3] vs. 5 [3-5], and 3 [2-3] vs. 5 [3-5], respectively; P< 0.05). Investigators' satisfaction scores, patients' anesthesia satisfaction scores, and anesthesia re-administration intention rate were significantly higher in group P than in group L (4 [3-5] vs. 3 [2-4], 2 [2-3] vs. 2 [1-3], 90.63% vs. 69.70%; P< 0.05). There was no significant intergroup difference in complications. CONCLUSIONS: Ultrasound-guided thoracic paravertebral block has similar safety to and better effectiveness than local anesthesia in PKP.

Single-Cell RNA Sequencing of Bone Marrow Mesenchymal Stem Cells from the Elderly People.

Background and Objectives: Bone marrow mesenchymal stem cells (BMSCs) show considerable promise in regenerative medicine. Many studies demonstrated that BMSCs cultured in vitro were highly heterogeneous and composed of diverse cell subpopulations, which may be the basis of their multiple biological characteristics. However, the exact cell subpopulations that make up BMSCs are still unknown. Methods and Results: In this study, we used single-cell RNA sequencing (scRNA-Seq) to divide 6,514 BMSCs into three clusters. The number and corresponding proportion of cells in clusters 1 to 3 were 3,766 (57.81%), 1,720 (26.40%), and 1,028 (15.78%). The gene expression profile and function of the cells in the same cluster were similar. The vast majority of cells expressed the markers defining BMSCs by flow cytometry and gene expression analysis. Each cluster had at least 20 differentially expressed genes (DEGs). We conducted Gene Ontology enrichment analysis on the top 20 DEGs of each cluster and found that the three clusters had different functions, which were related to self-renewal, multilineage differentiation and cytokine secretion, respectively. In addition, the function of the top 20 DEGs of each cluster was checked by the National Center for Biotechnology Information gene database to further verify our hypothesis. Conclusions: This study indicated that scRNA-Seq can be used to divide BMSCs into different subpopulations, demonstrating the heterogeneity of BMSCs.

Biochemical characterization and mutational studies of a thermostable endonuclease III from Sulfolobus islandicus REY15A.

Endonuclease III (EndoIII), which is ubiquitous in bacteria, Archaea and eukaryotes, plays an important role in excising thymine glycol (Tg) from DNA. Herein, we present evidence that an EndoIII from the hyperthermophilic crenarchaeon Sulfolobus islandicus REY15A (Sis-EndoIII) is capable of removing Tg from DNA at high temperature. Biochemical data show that the optimal temperature and pH of Sis-EndoIII are ca.70 °C and ca.7.0-8.0, respectively. Furthermore, the recombinant Sis-EndoIII retains relative weak activity without a divalent metal ion, and displays maximum activity in the presence of Mg2+ or Ca2+. Additionally, we first revealed the activation energy (Ea) of 39.7 ± 4.2 kcal/mol for Sis-EndoIII to remove Tg from dsDNA. As a bifunctional glycosylase, Sis-EndoIII possesses AP lyase activity in addition to glycosylase activity. Additionally, a covalent intermediate is formed between Sis-EndoIII and Tg-containing dsDNA. Mutational studies demonstrate that residues D50, K133 and D151 in Sis-EndoIII are responsible for removal of Tg from dsDNA and K133 and D151 are essential for formation of the covalent intermediate. To our knowledge, it is the first report of Tg excision by crenarchaeal EndoIII, thus augmenting our understanding on archaeal EndoIII function.

Safety and efficacy studies of kyphoplasty, mesh-container-plasty, and pedicle screw fixation plus vertebroplasty for thoracolumbar osteoporotic vertebral burst fractures.

BACKGROUND: Percutaneous kyphoplasty (PKP), percutaneous mesh-container-plasty (PMCP), and pedicle screw fixation plus vertebroplasty (PSFV) were three methods for osteoporotic vertebral burst fractures (OVBF). The purpose of the current study was to evaluate the clinical safety and efficacy of PKP, PMCP, and PSFV for OVBFs. METHODS: This retrospective study included 338 consecutive patients with thoracolumbar OVBFs who underwent PKP (n = 111), PMCP (n = 109), or PSFV (n = 118) and compared their epidemiological data, surgical outcomes, and clinical and radiological features. Clinical evaluations of VAS and ODI and radiological evaluations of height restoration, deformity correction, cement leakage, and canal compromise were calculated preoperatively, postoperatively, and 2 years postoperatively. RESULTS: Cement leakage (31/111 vs. 13/109 and 16/118, P < 0.05) was significantly higher in group PKP than in groups PSFV and PMCP. VAS and ODI scores improved postoperatively from 7.04 ± 1.15 and 67.11 ± 13.49 to 2.27 ± 1.04 and 22.00 ± 11.20, respectively, in group PKP (P < 0.05); from 7.04 ± 1.29 and 67.26 ± 12.79 to 2.17 ± 0.98 and 21.01 ± 7.90, respectively, in group PMCP (P < 0.05); and from 7.10 ± 1.37 and 67.36 ± 13.11 to 3.19 ± 1.06 and 33.81 ± 8.81, respectively, in the PSFV group (P < 0.05). Moreover, postoperative VAS and ODI scores were significantly higher in group PSFV than in groups PKP and PMCP (P < 0.05). However, VAS scores were not significantly different in the three groups 2 years postoperatively (P > 0.05). Postoperative anterior (81.04 ± 10.18% and 87.51 ± 8.94% vs. 93.46 ± 6.42%, P < 0.05) and middle vertebral body height ratio (83.01 ± 10.16% and 87.79 ± 11.62% vs. 92.38 ± 6.00%, P < 0.05) were significantly higher in group PSFV than in groups PMCP and PKP. Postoperatively, Cobb angle (10.04 ± 4.26° and 8.16 ± 5.76° vs. 4.97 ± 4.60°, P < 0.05) and canal compromise (20.76 ± 6.32 and 19.85 ± 6.18 vs. 10.18 ± 6.99, P < 0.05) were significantly lower in group PSFV than in groups PMCP and PKP. CONCLUSION: Despite relatively worse radiological results, PMCP is a safe and minimally invasive surgical method that can obtain better short-term clinical results than PKP and PSFV for OVBFs.

Percutaneous mesh-container-plasty for osteoporotic thoracolumbar burst fractures: A prospective, nonrandomized comparative study.

OBJECTIVE: This study aimed to compare the clinical and radiological results of percutaneous mesh-container-plasty (PMCP) versus percutaneous kyphoplasty (PKP) in the treatment of osteoporotic thoracolumbar burst fractures. METHODS: A prospective study of 122 patients with osteoporotic thoracolumbar burst fractures was conducted. The patients were nonrandomly assigned to receive PKP (62; 16 men, 46 women) and PMCP (60; 14 men, 46 women). The epidemiological data, surgical outcomes, and clinical and radiological features were compared between the 2 groups. Cement leakage, height restoration, deformity correction, canal compromise, and cement distribution were calculated from the radiographs. Visual pain analog scale (VAS), the Oswestry disability index (ODI), and short-form 36 health survey domains role physical (SF-36 rp) and bodily pain (SF-36 bp) were calculated before surgery and immediately and 2 years after surgery. RESULTS: Although VAS, ODI, SF-36 bp, and SF-36 rp scores improved from 7 (6-9), 71.28±16.38, 22 (0-32), and 25 (0-50) preoperatively to 2 (1-3), 20.02±8.97, 84 (84-84), and 75 (75-100) immediately postoperatively in the PMCP group (p<0.05) and from 7 (6-8), 71.40±13.52, 22 (10.5-31.75), and 25 (0-50) preoperatively to 2 (1-3), 21.78±11.21, 84 (84-84), and 75 (75-100) immediately postoperatively in the PKP group (p<0.05), there was no difference between the 2 groups. The mean cost in the PKP group was less than that in the PMCP group ($5109±231 vs. $6699±201, p<0.05). Anterior, middle, and posterior vertebral body height ratios in the PMCP group were greater than those in the PKP group postoperatively (88.44%±3.76% vs. 81.10%±11.78%, 86.15%±3.50% vs. 82.30%±11.02%, and 93.91%±3.01% vs. 91.43%±6.71%, respectively, p<0.05). The Cobb angle in the PMCP group was lower than that in the PKP group postoperatively (6.67°±4.39° vs. 8.99°±4.06°, p<0.05). Cement distribution in the PMCP group was higher than that in the PKP group (30.48%±5.62% vs. 27.18%±4.87%, p<0.05). Cement leakage was observed to be lesser in the PMCP group (2/60) than in the PKP group (10 vs. 62, p<0.05). CONCLUSION: Both PKP and PMCP treatments seem to have significant ability in pain relief and functional recovery. Despite its higher cost, PMCP treatment may have a better inhibition ability of cement leakage, cement distribution, height restoration, and improvement in segmental kyphosis than PKP treatment for osteoporotic thoracolumbar burst fractures. LEVEL OF EVIDENCE: Level II, Therapeutic Study.

Critical roles of sphingosine kinase 1 in the regulation of neuroinflammation and neuronal injury after spinal cord injury.

BACKGROUND: The pathological process of traumatic spinal cord injury (SCI) involves excessive activation of microglia leading to the overproduction of proinflammatory cytokines and causing neuronal injury. Sphingosine kinase 1 (Sphk1), a key enzyme responsible for phosphorylating sphingosine into sphingosine-1-phosphate (S1P), plays an important role in mediating inflammation, cell proliferation, survival, and immunity. METHODS: We aim to investigate the mechanism and pathway of the Sphk1-mediated neuroinflammatory response in a rodent model of SCI. Sixty Sprague-Dawley rats were randomly assigned to sham surgery, SCI, or PF543 (a specific Sphk1 inhibitor) groups. Functional outcomes included blinded hindlimb locomotor rating and inclined plane test. RESULTS: We discovered that Sphk1 is upregulated in injured spinal cord tissue of rats after SCI and is associated with production of S1P and subsequent NF-κB p65 activation. PF543 attenuated p65 activation, reduced inflammatory response, and relieved neuronal damage, leading to improved functional recovery. Western blot analysis confirmed that expression of S1P receptor 3 (S1PR3) and phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) are activated in microglia of SCI rats and mitigated by PF543. In vitro, we demonstrated that Bay11-7085 suppressed NF-κB p65 and inhibited amplification of the inflammation cascade by S1P, reducing the release of proinflammatory TNF-α. We further confirmed that phosphorylation of p38 MAPK and activation of NF-κB p65 is inhibited by PF543 and CAY10444. p38 MAPK phosphorylation and NF-κB p65 activation were enhanced by exogenous S1P and inhibited by the specific inhibitor SB204580, ultimately indicating that the S1P/S1PR3/p38 MAPK pathway contributes to the NF-κB p65 inflammatory response. CONCLUSION: Our results demonstrate a critical role of Sphk1 in the post-traumatic SCI inflammatory cascade and present the Sphk1/S1P/S1PR3 axis as a potential target for therapeutic intervention to control neuroinflammation, relieve neuronal damage, and improve functional outcomes in SCI.

Effect of synthetic oxygen-generating system on cell survival under hypoxic condition in vitro.

A significant challenge in the tissue engineering of injured sites is the lack of vascularization in the engineered sites due to insufficient oxygen supply. A scaffolding system is required to support seeded cells as vascularization develops. In this study, we examined the effects of hypoxic conditions and oxygen release on cell survival in a synthetic system. We developed a three-dimensional system using CaO2/poly(lactic-co-glycolic acid) microspheres suspended in a hydrogel. The system material was evaluated using stem cells under hypoxic conditions alongside controls to evaluate its oxygen-generating potential over a period of 21 days. The hydrogel acted as a flexible carrier supporting cell attachment and growth, protecting microspheres, and prolonging oxygen release. The system generated oxygen and supported cell growth, which are together expected to promote stem cell survival and growth in the weeks following implantation.