NIR Responsive Injectable Nanocomposite Thermogel System Against Osteosarcoma Recurrence.

Compared to traditional postoperative radiation and chemotherapy, immune checkpoint blockade (ICB) therapy demonstrates superiority by provoking own immune system to cure cancer completely even for some terminally ill patients. However, systemic administration of ICB is liable to cause severe immunity inflammation or immune storm. Here, an injectable, near infrared (NIR) responsive, multifunctional nanocomposite thermogel as a local ICB delivery system for cancer postsurgical therapy is proposed. By copolymerization of thermosensitive and zwitterionic monomer, the injectable thermogel with adjustable sol-gel transition temperature is obtained. Afterward, combined with functional mesoporous nanoparticles, the platform can absorb NIR light and transfer it into heat. The generated heat will promote retro Diels-Alder (D-A) reaction to degrade coating layer on nanoparticle, achieving NIR controlled ICB release. Furthermore, the local ICB delivery system is applied on an osteosarcoma postsurgical recurrence model and results indicate the platform with favorable biocompatibility can avoid early leakage of cargos and greatly increase drug content at tumor site. Besides, long-term controlled ICB release of the system effectively improves the amount of active T cells, resulting in excellent antitumor recurrence effect. Overall, this work suggests the local injectable nanocomposite thermogel is expected to be a promising tool for cancer postoperative therapy.

Clinical Investigation of the Association of Opening Size with Sagittal Canal Diameter Based on Single-Door Cervical Laminoplasty.

BACKGROUND Many clinical studies have assessed the association of laminoplasty opening size (LOS) with sagittal canal diameter (SCD) based on single-door cervical laminoplasty (SDCL). Nevertheless, the "worn-off" lamina extracted in SDCL was neglected in these reports. We aimed to develop a simple mathematical model to analyze the relationship between the effective LOS and SCD, taking into consideration the worn-off lamina. MATERIAL AND METHODS A total of 106 patients treated by SDCL at our hospital were included in this study. Pre-operative and post-operative SCDs were assessed using a picture archiving and communication system (PACS) based on computed tomography scans. Mini-plate sizes as well as drill bit diameters were recorded in detail in order to determine the effective LOS for each vertebral lamina involved. RESULTS SCD in all patients was increased significantly after SDCL (P<0.01). A linear correlation was found between effective LOS and the post-operative SCD increment from C3 to C7 (R²>0.933, P<0.001). The 12 mm mini-plate was most often used in SDCL, accounting for 64.45% of all cases, whereas 10 mm and 16 mm mini-plates were the least used, accounting for 3.85% and 3.00%, respectively. CONCLUSIONS There is a strong linear correlation between effective LOS and the post-operative SCD increment. The SCD was increased by about 0.5 mm per mm increase in effective LOS. Thus, post-operative SCD could be precisely calculated and predicted, enabling the selection of optimal mini-plate prior to SDCL.

A new method for calculating the desired laminoplasty opening size based on the target sagittal canal diameter before single-door cervical laminoplasty.

PURPOSE: To build a mathematical model which could calculate the desired laminoplasty opening size (LOS) based on the target sagittal canal diameter (SCD) before single-door cervical laminoplasty (SDCL) when taking the effects of surgery drill into consideration. METHODS: The model was based on geometric analysis on deformation of spinal canal; the formula was derived and characterized as: y (mm) = 2 [Formula: see text] × sin(ß/2) = c - d (y is the size of LOS, [Formula: see text] the size of transverse canal diameter, ß the size of laminoplasty opening size, c the size of mini-plate and d the diameter of the drill bit used during the surgery operation). The parameters of pre- and postoperative computed tomography scans of 20 patients who had undergone SDCL were measured by the picture archiving and communication system (PACS) software and a new instrument named as Lei's ruler, respectively. RESULTS: The effects of surgery SDCL were very significant; for each patient, the SCD was enlarged dramatically after the surgery (P < 0.01). The differences between the data obtained by PACS and Lei's ruler were no statistically significant (P > 0.05). According to the derived formula, the 95% confidence intervals of SCD after the surgery were within the range of 14 mm and 14.5 mm. CONCLUSION: Applying the mathematical model and derived formula, the desired LOS could be calculated according to the target SCD which could help the surgeon select an optimum mini-plate before SDCL. At the same time, a new measuring device named Lei's ruler is designed for the convenience of the derived formula. These slides can be retrieved under Electronic Supplementary Material.

Ex Vivo Evaluation of Hip Fracture Risk by Proximal Femur Geometry and Bone Mineral Density in Elderly Chinese Women.

BACKGROUND The incidence of hip fracture is steadily increasing. We aimed to establish a creative approach to precisely estimate the risk of hip fracture by exploring the relationship between hip fracture and bone mineral density (BMD)/femur geometry. MATERIAL AND METHODS Sixteen samples of cadaveric female proximal femora were randomly selected. Experiments were performed experimental measurement of the femoral neck BMD and geometric parameters (including neck length, neck diameter, head diameter, and neck-shaft angle). In addition, the experimental measurements contain the failure load, which represents the mechanical strength of the femoral neck, and we calculated the correlation coefficient among BMD, geometric parameters, and failure load. RESULTS Significant correlations were discovered between femoral mechanical properties and femoral neck BMD (r=0.792, r²=0.628, P<0.001), trochanteric BMD (r=0.749, r²=0.560, P=0.001), and head diameter (r=0.706, r²=0.499, P=0.002). Multiple linear regression analyses indicated that the best predictor of hip fracture was the combination of femoral neck BMD, head diameter, and neck diameter (r²=0.844, P<0.001). CONCLUSIONS The results confirmed that, compared with BMD alone, the combination of BMD and geometric parameters of proximal femur is a better estimation of hip fracture. The geometry of the proximal femur played an important role in assessing the biomechanical strength of femur. This method greatly assists in predicting the risk of hip fracture in clinical trials and will assist studies on why the incidence of hip fracture varies among races.

Which level is responsible for gluteal pain in lumbar disc hernia?

BACKGROUND: There are many different reasons why patients could be experiencing pain in the gluteal area. Previous studies have shown an association between radicular low back pain (LBP) and gluteal pain (GP). Studies locating the specific level responsible for gluteal pain in lumbar disc hernias have rarely been reported. METHODS: All patients with lumbar disc herniation (LDH) in the Kanghua hospital from 2010 to 2014 were recruited. All patients underwent a lumbar spine MRI to clarify their LDH diagnosis, and patients were allocated to a GP group and a non-GP group. To determine the cause and effect relationship between LDH and GP, all of the patients were subjected to percutaneous endoscopic lumbar discectomy (PELD). RESULTS: A total of 286 cases were included according to the inclusive criteria, with 168 cases in the GP group and 118 cases in the non-GP group. Of these, in the GP group, 159 cases involved the L4/5 level and 9 cases involved the L5/S1 level, while in the non-GP group, 43 cases involved the L4/5 level and 48 cases involved the L5/S1 level. PELD was performed in both groups. Gluteal pain gradually disappeared after surgery in all of the patients. Gluteal pain recrudesced in a patient with recurrent disc herniation (L4/5). CONCLUSIONS: As a clinical finding, gluteal pain is related to low lumbar disc hernia. The L4/5 level is the main level responsible for gluteal pain in lumbar disc hernia. No patients with gluteal pain exhibited involvement at the L3/4 level.

A novel total cervical prosthesis for single-level cervical subtotal corpectomy: radiologic and histomorphometric analysis in a caprine model.

STUDY DESIGN: A novel total cervical prosthesis (TCP) for single-level cervical subtotal corpectomy was assessed in a caprine animal model. OBJECTIVES: To investigate the radiologic and histomorphometric characteristics of a novel TCP for single-level cervical subtotal corpectomy. SUMMARY OF BACKGROUND: Cervical disk replacement has emerged as a promising alternative to arthrodesis in the management of cervical disk herniation. However, they are designed for anterior cervical discectomy, and not suitable for cervical subtotal corpectomy. To solve this problem, our group has developed a novel TCP for single-level cervical subtotal corpectomy. MATERIALS AND METHODS: There were 12 adult Shannxi goats (2 y old) used in this study. The goats were divided into 2 groups based on postoperative survival periods of 3 (n=6) and 6 (n=6) months after surgery. Using an anterior surgical approach, a standard anterior C3 vertebra subtotal corpectomy and decompression of the spinal canal were performed, followed by implantation of the TCP device. Then all the goats were killed and underwent radiographic and histologic observations. RESULTS: The TCP implant procedures were successfully completed in all 12 goats without incidence of vascular or infectious complications. The range of motion of C2-C3 and C3-C4 segments were preserved in both of the groups. Three-dimensional images of specimens interface indicated confluent interdigitization of trabeculae at the prosthetic endplate-bone interface, without evidence of significant radiolucent lines or gaps. Histomorphometric analysis showed that there were a large number of fibrous tissue and a small amount of cartilage cells between the prostheses and bone in the 3 months' group. In the 6 months' group, part of fibrous tissue has changed into the cartilage tissue. CONCLUSIONS: Our data show that this prosthesis can maintain the stability of the cervical spine and retain the activity of the cervical spine in vivo. The findings in this study provide a foundation for ongoing clinical investigations using the TCP.

miR-18a-5p promotes osteogenic differentiation of BMSC by inhibiting Notch2.

Postmenopausal osteoporosis (PMOP) is a metabolic disorder characterized by the loss of bone density, which increases the risk of developing complications such as fractures. A pivotal factor contributing to the onset of PMOP is the diminished osteogenic differentiation capacity of bone marrow mesenchymal stem cells (BMSCs). MicroRNAs (miRNAs) play a substantial role in this process; however, their specific impact on regulating BMSCs osteogenesis remains unclear. Studies have evidenced a reduced expression of miR-18a-5p in PMOP, and concomitantly, our observations indicate an augmented expression of miR-18a-5p during the osteogenic differentiation of BMSCs. This investigation seeks to elucidate the regulatory influence of miR-18a-5p on BMSC osteogenic differentiation and the underlying mechanisms. In vitro experiments demonstrated that the overexpression of miR-18a-5p facilitated the osteogenic differentiation of BMSCs, while the downregulation of miR-18a-5p yielded converse outcomes. Mechanistically, We employed bioinformatics techniques to screen out the target gene Notch2 of miR-18a-5p. Subsequently, dual-luciferase reporter gene assays and rescue experiments substantiated that miR-18a-5p promotes BMSC osteogenic differentiation by suppressing Notch2. Finally, miR-18a-5p was overexpressed via adenovirus injection into the femoral bone marrow cavity, with results demonstrating its capability to enhance osteogenic differentiation and alleviate PMOP symptoms. Our findings disclose that miR-18a-5p fosters osteogenic differentiation of BMSC by inhibiting Notch2, thereby offering novel targets and strategies for PMOP treatment.

Localized delivery of metformin via 3D printed GelMA-Nanoclay hydrogel scaffold for enhanced treatment of diabetic bone defects.

Background: Diabetic bone defects present significant challenges for individuals with diabetes. While metformin has been explored for bone regeneration via local delivery, its application in treating diabetic bone defects remains under-explored. In this study, we aim to leverage 3D printing technology to fabricate a GelMA-Nanoclay hydrogel scaffold loaded with metformin specifically for this purpose. The objective is to assess whether the in situ release of metformin can effectively enhance osteogenesis, angiogenesis, and immunomodulation in the context of diabetic bone defects. Materials and methods: Utilizing 3D printing technology, we constructed a GelMA-Nanoclay-Metformin hydrogel scaffold with optimal physical properties and biocompatibility. The osteogenic, angiogenic, and immunomodulatory characteristics of the hydrogel scaffold were thoroughly investigated through both in vitro and in vivo experiments. Results: GelMA10%-Nanoclay8%-Metformin5mg/mL was selected as the bioink for 3D printing due to its favorable swelling rate, degradation rate, mechanical strength, and drug release rate. Through in vitro investigations, the hydrogel scaffold extract, enriched with metformin, demonstrated a substantial enhancement in the proliferation and migration of BMSCs within a high-glucose microenvironment. It effectively enhances osteogenesis, angiogenesis, and immunomodulation. In vivo experimental outcomes further underscored the efficacy of the metformin-loaded GelMA-Nanoclay hydrogel scaffold in promoting superior bone regeneration within diabetic bone defects. Conclusions: In conclusion, while previous studies have explored local delivery of metformin for bone regeneration, our research is pioneering in its application to diabetic bone defects using a 3D printed GelMA-Nanoclay hydrogel scaffold. This localized delivery approach demonstrates significant potential for enhancing bone regeneration in diabetic patients, offering a novel approach for treating diabetic bone defects. The translational potential of this article: Our study demonstrates, for the first time, the successful loading of the systemic antidiabetic drug metformin onto a hydrogel scaffold for localized delivery. This approach exhibits significant efficacy in mending diabetic bone defects, presenting a promising new avenue for the treatment of such conditions.

Inadequate anticoagulation and hyperuricemia cause knee pain after platelet-rich plasma injection: A retrospective study.

OBJECTIVES: Platelet-rich plasma treatment delays the need for total knee replacement in patients with knee osteoarthritis. However, its use and preparation remain controversial. The aim of this study was to investigate the relationship between anticoagulant use in the preparation of platelet-rich plasma and post-treatment pain in patients with knee osteoarthritis. Additionally, we explored the efficacy of platelet-rich plasma over medium- and long-term follow-up periods and identified other factors that may affect treatment outcomes. METHODS: In this retrospective study, 225 patients with knee osteoarthritis, who underwent knee platelet-rich plasma treatment from June 2021 to January 2022, were examined at three study centres. Patients were categorised, based on the type and amount of anticoagulant used during platelet-rich plasma preparation, into 4% sodium citrate (SC) 0.6 mL, 4% SC 1 mL, 4% SC 2 mL, heparin 0.1 mL, and heparin 0.2 mL groups. We analysed the patients' basic information, pain after treatment, and inflammatory markers (i.e., interleukin 6, tumour necrosis factor-α, and hypersensitive C-reactive protein) in the joint fluid via enzyme-linked immunosorbent assay and joint fluid crystallisation. Additionally, we assessed the patients' Western Ontario and McMaster University scores and minimal clinically significant differences after treatment. RESULTS: Patients in the 4% SC 0.6 mL and heparin 0.1 mL groups experienced less pain after platelet-rich plasma treatment than did patients in the high-dose anticoagulant group. The joint fluid of patients with pain in these groups had lower levels of inflammatory markers. Patients treated with SC had slightly better medium- and long-term therapeutic outcomes than did patients treated with heparin. Patients with poorly controlled hyperuricemia also experienced pain after platelet-rich plasma treatment. CONCLUSIONS: The results suggest that platelet-rich plasma prepared using high-dose anticoagulants or administered to patients with poorly controlled hyperuricaemia may lead to moderate-to-severe knee pain and joint effusion after joint puncture therapy. Platelet-rich plasma had a therapeutic effect on knee osteoarthritis; however, its efficacy gradually decreased over time. SC anticoagulant is more suitable for platelet-rich plasma preparation than is heparin. Further studies are needed to understand the safety and the various factors influencing platelet-rich plasma therapy.

A mechanical-assisted post-bioprinting strategy for challenging bone defects repair.

Bioprinting that can synchronously deposit cells and biomaterials has lent fresh impetus to the field of tissue regeneration. However, the unavoidable occurrence of cell damage during fabrication process and intrinsically poor mechanical stability of bioprinted cell-laden scaffolds severely restrict their utilization. As such, on basis of heart-inspired hollow hydrogel-based scaffolds (HHSs), a mechanical-assisted post-bioprinting strategy is proposed to load cells into HHSs in a rapid, uniform, precise and friendly manner. HHSs show mechanical responsiveness to load cells within 4 s, a 13-fold increase in cell number, and partitioned loading of two types of cells compared with those under static conditions. As a proof of concept, HHSs with the loading cells show an enhanced regenerative capability in repair of the critical-sized segmental and osteoporotic bone defects in vivo. We expect that this post-bioprinting strategy can provide a universal, efficient, and promising way to promote cell-based regenerative therapy.

Oyster mantle-derived exosomes alleviate osteoporosis by regulating bone homeostasis.

Osteoporosis is a major public health problem with an urgent need for safe and effective therapeutic interventions. The process of shell formation in oysters is similar to that of bone formation in mammals, and oyster extracts have been proven to exert osteoprotective effects. Oyster mantle is the most crucial organ regulating shell formation, in which exosomes play an important role. However, the effects of oyster mantle-derived exosomes (OMEs) on mammalian osteoporosis and the underlying mechanisms remain unknown. The OMEs investigated herein was found to carry abundant osteogenic cargos. They could also survive hostile gastrointestinal conditions and accumulate in the bones following oral administration. Moreover, they promoted osteoblastic differentiation and inhibited osteoclastic differentiation simultaneously. Further mechanistic examination revealed that OMEs likely promoted osteogenic activity by activating PI3K/Akt/ß-catenin pathway in osteoblasts and blunted osteoclastic activity by inhibiting NF-κB pathway in osteoclasts. These favorable pro-osteogenic effects of OMEs were also corroborated in a rat femur defect model. Importantly, oral administration of OMEs effectively attenuated bone loss and improved the bone microstructure in ovariectomy-induced osteoporotic mice, and demonstrating excellent biosafety. The mechanistic insights from our data support that OMEs possess promising therapeutic potential against osteoporosis.

Effect of injectable calcium alginate-amelogenin hydrogel on macrophage polarization and promotion of jawbone osteogenesis.

Due to persistent inflammation and limited osteogenesis, jawbone defects present a considerable challenge in regenerative medicine. Amelogenin, a major protein constituent of the developing enamel matrix, demonstrates promising capabilities in inducing regeneration of periodontal supporting tissues and exerting immunomodulatory effects. These properties render it a potential therapeutic agent for enhancing jawbone osteogenesis. Nevertheless, its clinical application is hindered by the limitations of monotherapy and its rapid release characteristics, which compromise its efficacy and delivery efficiency. In this context, calcium alginate hydrogel, recognized for its superior physicochemical properties and biocompatibility, emerges as a candidate for developing a synergistic bioengineered drug delivery system. This study describes the synthesis of an injectable calcium amelogenin/calcium alginate hydrogel using calcium alginate loaded with amelogenin. We comprehensively investigated its physical properties, its role in modulating the immunological environment conducive to bone healing, and its osteogenic efficacy in areas of jawbone defects. Our experimental findings indicate that this synthesized composite hydrogel possesses desirable mechanical properties such as injectability, biocompatibility, and biodegradability. Furthermore, it facilitates jawbone formation by regulating the bone-healing microenvironment and directly inducing osteogenesis. This research provides novel insights into the development of bone-tissue regeneration materials, potentially advancing their clinical application.

Application of image recognition-based tracker-less augmented reality navigation system in a series of sawbone trials.

BACKGROUND: This study introduced an Augmented Reality (AR) navigation system to address limitations in conventional high tibial osteotomy (HTO). The objective was to enhance precision and efficiency in HTO procedures, overcoming challenges such as inconsistent postoperative alignment and potential neurovascular damage. METHODS: The AR-MR (Mixed Reality) navigation system, comprising HoloLens, Unity Engine, and Vuforia software, was employed for pre-clinical trials using tibial sawbone models. CT images generated 3D anatomical models, projected via HoloLens, allowing surgeons to interact through intuitive hand gestures. The critical procedure of target tracking, essential for aligning virtual and real objects, was facilitated by Vuforia's feature detection algorithm. RESULTS: In trials, the AR-MR system demonstrated significant reductions in both preoperative planning and intraoperative times compared to conventional navigation and metal 3D-printed surgical guides. The AR system, while exhibiting lower accuracy, exhibited efficiency, making it a promising option for HTO procedures. The preoperative planning time for the AR system was notably shorter (4 min) compared to conventional navigation (30.5 min) and metal guides (75.5 min). Intraoperative time for AR lasted 8.5 min, considerably faster than that of conventional navigation (31.5 min) and metal guides (10.5 min). CONCLUSIONS: The AR navigation system presents a transformative approach to HTO, offering a trade-off between accuracy and efficiency. Ongoing improvements, such as the incorporation of two-stage registration and pointing devices, could further enhance precision. While the system may be less accurate, its efficiency renders it a potential breakthrough in orthopedic surgery, particularly for reducing unnecessary harm and streamlining surgical procedures.

Clinical assessment of a CMC/PEO gel to inhibit postoperative epidural adhesion formation after lumbar discectomy: a randomized, control study.

PURPOSE: To evaluate effectiveness of carboxymethylcellulose/polyethylene oxide (CMC/PEO) gel in improving clinical outcomes after the first-time lumbar discectomy. METHOD: Ninety-three patients with herniated lumbar disc at L4-L5 or L5-S1 were enrolled and randomized into two groups: CMC/PEO gel treatment group and control group. All the patients underwent laminotomy and discectomy by posterior approach. The preoperative and postoperative Oswestry Disability Index (ODI) and Visual Analogue Scale (VAS) scores for lower-back pain and leg pain were analyzed and compared between two groups at 30- and 60-day time points. RESULTS: No patient presented with any clinically measurable adverse event during surgery. There were no significant differences between the treated group and the control group on the preoperative ODI and VAS scores. In general, the ODI and VAS scores decreased in both groups at all the time points. At the 30-day time point, the VAS scores for back pain and leg pain and the ODI scores in treatment group were lower by 9.9 % (P = 0.0302), 27.0 % (P = 0.0002) and 16.3 % (P = 0.0007) than those in control group. And at the 60-day time point, the ODI and VAS scores further decreased in both groups. The VAS scores for leg pain in treatment group were lower by 4.5 % than that in the control group (P = 0.0149). However, no significant difference was detected between two groups on the ODI and VAS scores for back pain. CONCLUSIONS: The results demonstrated that CMC/PEO gel is effective in reducing posterior dural adhesions in the spine with no apparent safety issues. It can improve patients' postoperative clinical outcome.

Bone marrow mesenchymal stem cell-derived exosomes attenuate the maturation of dendritic cells and reduce the rejection of allogeneic transplantation.

BACKGROUND: Bone mesenchymal stem cell (BMSC)-derived exosomes (B-exos) are attractive for applications in enabling alloantigen tolerance. An in-depth mechanistic understanding of the interaction between B-exos and dendritic cells (DCs) could lead to novel cell-based therapies for allogeneic transplantation. OBJECTIVES: To examine whether B-exos exert immunomodulatory effects on DC function and maturation. MATERIAL AND METHODS: After mixed culture of BMSCs and DCs for 48 h, DCs from the upper layer were collected to analyze the expression levels of surface markers and mRNAs of inflammation-related cytokines. Then, before being collected to detect the mRNA and protein expression levels of indoleamine 2,3-dioxygenase (IDO), the DCs were co-cultured with B-exos. Then, the treated DCs from different groups were co-cultured with naïve CD4+ T cells from the mouse spleen. The proliferation of CD4+ T cells and the proportion of CD4+CD25+Foxp3+ T cells were analyzed. Finally, the skins of BALB/c mice were transplanted to the back of C57 mice in order to establish a mouse allogeneic skin transplantation model. RESULTS: The co-culture of DCs with BMSCs downregulated the expression of the major histocompatibility complex class II (MHC-II) and CD80/86 costimulatory molecules on DCs. Moreover, B-exos increased the expression of IDO in DCs treated with lipopolysaccharide (LPS). The proliferation of CD4+CD25+Foxp3+ T cells increased when cultured with B-exos-exposed DCs. Finally, mice recipients injected with B-exos-treated DCs had significantly prolonged survival after receiving the skin allograft. CONCLUSIONS: Taken together, these data suggest that the B-exos suppress the maturation of DCs and increase the expression of IDO, which might shed light on the role of B-exos in inducing alloantigen tolerance.

3D printed PLGA/MgO/PDA composite scaffold by low-temperature deposition manufacturing for bone tissue engineering applications.

Introduction: Bones are easily damaged. Biomimetic scaffolds are involved in tissue engineering. This study explored polydopamine (PDA)-coated poly lactic-co-glycolic acid (PLGA)-magnesium oxide (MgO) scaffold properties and its effects on bone marrow mesenchymal stem cells (BMSCs) osteogenic differentiation. Methods: PLGA/MgO scaffolds were prepared by low-temperature 3D printing technology and PDA coatings were prepared by immersion method. Scaffold structure was observed by scanning electron microscopy with an energy dispersive spectrometer (SEM-EDS), fourier transform infrared spectrometer (FTIR). Scaffold hydrophilicity, compressive/elastic modulus, and degradation rates were analyzed by water contact angle measurement, mechanical tests, and simulated-body fluid immersion. Rat BMSCs were cultured in scaffold extract. Cell activity on days 1, 3, and 7 was detected by MTT. Cells were induced by osteogenic differentiation, followed by evaluation of alkaline phosphatase (ALP) activity on days 3, 7, and 14 of induction and Osteocalcin, Osteocalcin, and Collagen I expressions. Results: The prepared PLGA/MgO scaffolds had dense microparticles. With the increase of MgO contents, the hydrophilicity was enhanced, scaffold degradation rate was accelerated, magnesium ion release rate and scaffold extract pH value were increased, and cytotoxicity was less when magnesium mass ratio was less than 10%. Compared with other scaffolds, compressive and elastic modulus of PLGA/MgO (10%) scaffolds were increased; BMSCs incubated with PLGA/MgO (10%) scaffold extract had higher ALP activity and Osteocalcin, Osteopontin, and Collagen I expressions. PDA coating was prepared in PLGA/MgO (10%) scaffolds and the mechanical properties were not affected. PLGA/MgO (10%)/PDA scaffolds had better hydrophilicity and biocompatibility and promoted BMSC osteogenic differentiation. Conclusion: Low-temperature 3D printing PLGA/MgO (10%)/PDA scaffolds had good hydrophilicity and biocompatibility, and were conducive to BMSC osteogenic differentiation.

Exploiting antitumor immunity to overcome relapse and improve remission duration.

Cancer survivors often relapse due to evolving drug-resistant clones and repopulating tumor stem cells. Our preclinical study demonstrated that terminal cancer patient's lymphocytes can be converted from tolerant bystanders in vivo into effective cytotoxic T-lymphocytes in vitro killing patient's own tumor cells containing drug-resistant clones and tumor stem cells. We designed a clinical trial combining peginterferon α-2b with imatinib for treatment of stage III/IV gastrointestinal stromal tumor (GIST) with the rational that peginterferon α-2b serves as danger signals to promote antitumor immunity while imatinib's effective tumor killing undermines tumor-induced tolerance and supply tumor-specific antigens in vivo without leukopenia, thus allowing for proper dendritic cell and cytotoxic T-lymphocyte differentiation toward Th1 response. Interim analysis of eight patients demonstrated significant induction of IFN-γ-producing-CD8(+), -CD4(+), -NK cell, and IFN-γ-producing-tumor-infiltrating-lymphocytes, signifying significant Th1 response and NK cell activation. After a median follow-up of 3.6 years, complete response (CR) + partial response (PR) = 100%, overall survival = 100%, one patient died of unrelated illness while in remission, six of seven evaluable patients are either in continuing PR/CR (5 patients) or have progression-free survival (PFS, 1 patient) exceeding the upper limit of the 95% confidence level of the genotype-specific-PFS of the phase III imatinib-monotherapy (CALGB150105/SWOGS0033), demonstrating highly promising clinical outcomes. The current trial is closed in preparation for a larger future trial. We conclude that combination of targeted therapy and immunotherapy is safe and induced significant Th1 response and NK cell activation and demonstrated highly promising clinical efficacy in GIST, thus warranting development in other tumor types.

Surgical treatment of osteoporotic thoracolumbar compressive fractures with open vertebral cement augmentation of expandable pedicle screw fixation: a biomechanical study and a 2-year follow-up of 20 patients.

BACKGROUND: The incidence of screw loosening increases significantly in elderly patients with severe osteoporosis. Open vertebral cement augmentation of expandable pedicle screw fixation may improve fixation strength in the osteoporotic vertebrae. MATERIALS AND METHODS: Twenty cadaveric vertebrae (L1-L5) were harvested from six osteoporotic lumbar spines. Axial pullout tests were performed to compare the maximum pullout strength (Fmax) of four methods: 1. Conventional pedicle screws (CPS), 2. Expandable pedicle screws (EPS), 3. Cement augmentation of CPS (cemented-CPS), 4. Cement augmentation of EPS (cemented-EPS). Thirty-six consecutive patients with single-vertebral osteoporotic compressive fractures received posterior decompression and spinal fusion with cemented-CPS (16 cases) or cemented-EPS (20 cases). Plain film and/or CT scan were conducted to evaluate the spinal fusion and fixation effectiveness. RESULTS: The Fmax and energy absorption of cemented-EPS were significantly greater than three control groups. The mean BMD in the severe osteoporosis group was significantly lower than that in the osteoporosis group (t = 2.04, P = 0.036). In the osteoporosis group, cemented-EPS improved the Fmax by 43% and 21% over CPS and cemented-CPS group. In the severe osteoporosis group, cemented-EPS increased the Fmax by 59%, 22%, and 26% over CPS, EPS, and cemented-CPS, respectively. The clinical results showed that all patients suffered from severe osteoporosis. Six months after operation, the JOA and VAS scores in cemented-EPS group improved from 11.4 ± 2.6 and 7.0 ± 1.4 mm to 24.9 ± 1.6 and 2.1 ± 1.3 mm, respectively. No screw loosening occurred in the cemented-EPS group and spinal fusion was achieved. In the cemented-CPS group, four screws loosened (4.2%) according to the radiolucency. Six months after operation, the JOA and VAS scores improved from 13.1 ± 1.9 and 7.6 ± 1.5 mm to 22.8 ± 2.2 and 2.5 ± 1.6 mm, respectively. No cement leaked into the spinal canal in both groups. CONCLUSIONS: Cemented-EPS could increase fixation strength biomechanically. It could reduce the risks of screw loosening in patients with severe osteoporosis, requiring instrumented arthrodesis.

A comparative study on screw loosening in osteoporotic lumbar spine fusion between expandable and conventional pedicle screws.

INTRODUCTION: The aim of this study is to compare the rate of screw loosening and clinical outcomes of expandable pedicle screws (EPS) with those of conventional pedicle screws (CPS) in patients treated for spinal stenosis (SS) combined with osteoporosis. METHODS: One hundred and fifty-seven consecutive patients with SS received either EPS fixation (n = 80) or CPS fixation (n = 77) to obtain lumbosacral stabilization. Patients were observed for a minimum of 24 months. Outcome measures included screw loosening, fusion rate, Japanese Orthopaedic Association (JOA) scores and Oswestry disability index (ODI) scoring system, and complications. RESULTS: In the EPS group, 20 screws became loose (4.1%) in 6 patients (7.5%), and two screws (0.4%) had broken. In the CPS group, 48 screws became loose (12.9%) in 15 patients (19.5%), but no screws were broken. The fusion rate in the EPS group (92.5%) was significantly higher than that of the CPS group (80.5%). The rate of screw loosening in the EPS group (4.1%) was significantly lower than that of the CPS group (12.9%). Six EPS (1.8%) screws were removed. In the EPS group, two screws had broken but without neural complications. Twelve months after surgeries, JOA and ODI scores in the EPS group were significantly improved. There were four cases of dural tears, which healed after corresponding treatment. CONCLUSIONS: EPS can decrease the risk of screw loosening and achieve better fixation strength and clinical results in osteoporotic lumbar spine fusion.

Biomechanical Evaluation and Preliminary Clinical Results of Anterolateral Screw Fixation for Oblique Lumbar Interbody Fusion Surgery.

BACKGROUND: The most common complication of oblique lumbar interbody fusion (OLIF) is endplate fracture/subsidence. The aim of this study was to evaluate biomechanical stability in patients undergoing OLIF surgery with anterolateral screw fixation (ASF). METHODS: Based on a previously validated model technique, L4-L5 functional surgical models corresponding to the ASF and bilateral pedicle screw fixation (BPSF) methods were created. Finite element models were developed to compare the biomechanics of the ASF and BPSF groups. We retrospectively analyzed 18 patients with lumbar degenerative diseases who underwent OLIF with ASF in Shenzhen Hospital of Southern Medical University from April 2020 to April 2021. Intraoperative and postoperative complications were observed. RESULTS: Compared with the BPSF model, the maximum stresses of the L4 inferior endplate and L5 superior endplate were greatly increased in the ASF model. The contact surface between the vertebrae and screw (CSVS) in the ASF model produced nearly 100% more stress than the BPSF model at all moments. In clinical practice, after a 12-month follow-up, 7 adverse events were observed, including 3 cases of left thigh pain/numbness, 3 cases of cage subsidence, and 1 case of screw loosening. CONCLUSIONS: OLIF surgery with ASF could not reduce the maximum stresses on the endplate and CSVS, which may be a potential risk factor for cage subsidence and screw loosening.