Senescence-targeted MicroRNA/Organoid composite hydrogel repair cartilage defect and prevention joint degeneration via improved chondrocyte homeostasis.

Introduction: Cartilage defect (CD) is a common complication in osteoarthritis (OA). Impairment of chondrogenesis and cellular senescence are considered as hallmarks of OA development and caused failure of cartilage repair in most clinical CD cases. Exploring markers for cellular senescence in CD patients might provide new perspectives for osteoarthritic CD patients. In the present study, we aim to explore senescent markers in CD patients with OA to fabricate a senescence-targeted SMSC organoid hydrogel for cartilage repair. Methods: Clinical cartilage samples from cartilage defect patients were collected. Immunofluorescence staining of senescent markers and SA-ß-Gal staining were used to detect the senescence state of SMSCs and chondrocytes in cartilage defect and OA patients. MicroRNA expression profiles of SMSC organoids and H2O2-treated SMSC organoids were analyzed and compared with high-throughput microRNA sequencing. Fluorescent in situ hybridization of miRNA were used to determine the expression level of miR-24 in SMSC organoids and cartilage samples. Interaction between miR-24 and its downstream target was analyzed via qRT-PCR, immunofluorescence and luciferase assay. Senescence-targeted miR-24 µS/SMSC organoid hydrogel (MSOH) was constructed for cartilage repair. Anti-senescence properties and chondrogenesis were determined in vitro for MSOH. Rats were used to evaluate the cartilage repair capacity of the MSOH hydrogel in vivo. Results: In this study, we found Osteoarthritic cartilage defect patients demonstrated upregulated cellular senescence in joint cartilage. MicroRNA sequencing demonstrated senescence marker miR-24 was negatively associated with cartilage impairment and cellular senescence in osteoarthritic CD patients. Moreover, miR-24 mimics alleviates cellular senescence to promote chondrogenesis by targeting downstream TAOK1. Also, miR-24 downregulated TAOK1 expression and promoted chondrogenesis in SMSC organoids. Senescence-targeted miR-24 µS/SMSC organoid hydrogel (MSOH) was constructed and demonstrated superior chondrogenesis in vitro. Animal experiments demonstrated that MSOH hydrogel showed better cartilage repairing effects and better maintained joint function at 24 weeks with low intra-articular inflammatory response after transplantation in rat joint. Single-cell RNA-seq of generated cartilage indicated that implanted MSOH could affect chondrocyte homeostatic state and alter the chondrocyte cluster frequency by regulating cellular glycolysis and OXPHOS, impacting cell cycle and ferroptosis to alleviate cellular senescence and prevent joint degeneration. Conclusion: Osteoarthritic cartilage defect patients demonstrated upregulated cellular senescence in joint cartilage. Senescence marker miR-24 was negatively associated with cartilage impairment in osteoarthritic CD patients. miR-24 attenuates chondrocytes senescence and promotes chondrogenesis in SMSC organoids through targeting TAOK1. Senescence-targeted miR-24 microsphere/SMSC organoid composite hydrogel could successfully repair cartilage defect in osteoarthritic microenvironment via enhanced miR-24/TAOK1 signaling pathway, suggesting MSOH might be a novel therapy for cartilage repair in osteoarthritic CD patients.

An adaptive biodegradable zinc alloy with bidirectional regulation of bone homeostasis for treating fractures and aged bone defects.

Healing of fractures or bone defects is significantly hindered by overactivated osteoclasts and inhibited osteogenesis in patients with abnormal bone metabolism. Current clinical approaches using titanium alloys or stainless steel provide mechanical support but have no biological effects on bone regeneration. Therefore, designing and fabricating degradable metal materials with sufficient mechanical strength and bidirectional regulation of both osteoblasts and osteoclasts is a substantial challenge. Here, this study first reported an adaptive biodegradable Zn-0.8 Mg alloy with bidirectional regulation of bone homeostasis, which promotes osteogenic differentiation by activating the Pi3k/Akt pathway and inhibits osteoclast differentiation by inhibiting the GRB2/ERK pathway. The anti-osteolytic ability of the Zn-0.8 Mg alloy was verified in a mouse calvarial osteolysis model and its suitability for internal fracture fixation with high-strength screws was confirmed in the rabbit femoral condyle fracture model. Furthermore, in an aged postmenopausal rat femoral condyle defect model, 3D printed Zn-0.8 Mg scaffolds promoted excellent bone regeneration through adaptive structures with good mechanical properties and bidirectionally regulated bone metabolism, enabling personalized bone defect repair. These findings demonstrate the substantial potential of the Zn-0.8 Mg alloy for treating fractures or bone defects in patients with aberrant bone metabolism.

Genetically inspired organoids prevent joint degeneration and alleviate chondrocyte senescence via Col11a1-HIF1α-mediated glycolysis-OXPHOS metabolism shift.

INTRODUCTION: Developmental dysplasia of hip (DDH) is a hip joint disorder leading to subsequent osteoarthritis. Previous studies suggested collagen XI alpha 1 (COL11A1) as a potential gene in hip dysplasia and chondrocyte degeneration. However, no genetic association has reported COL11A1-related cellular therapy as treatment of DDH and joint degeneration. METHODS AND RESULTS: We report identified genetic association between COL11A1 locus and DDH with genome-wide association study (GWAS). Further exome sequencing for familial DDH patients was conducted in different populations to identify potential pathogenic Col11A1 variants for familiar DDH. Further studies demonstrated involvement of COL11A1 expression was down-regulated in femoral head cartilage of DDH patients and Col11a1-KO mice with induced DDH. Col11a1-KO mice demonstrated aggravated joint degeneration and severe OA phenotype. To explore the underlying mechanism of Col11a1 in cartilage and DDH development, we generated scRNA-seq profiles for DDH and Col11a1-KO cartilage, demonstrating disrupted chondrocyte homeostasis and cellular senescence caused by Col11a1-HIF1α-mediated glycolysis-OXPHOS shift in chondrocytes. Genetically and biologically inspired, we further fabricated an intra-articular injection therapy to preventing cartilage degeneration by generating a Col11a1-over-expressed (OE) SMSC mini-organoids. Col11a1-OE organoids demonstrated superior chondrogenesis and ameliorated cartilage degeneration in DDH mice via regulating cellular senescence by up-regulated Col11a1/HIF1α-mediated glycolysis in chondrocytes. CONCLUSION: We reported association between COL11A1 loci and DDH with GWAS and exome sequencing. Further studies demonstrated involvement of COL11A1 in DDH patients and Col11a1-KO mice. ScRNA-seq for DDH and Col11a1-KO cartilage demonstrated disrupted chondrocyte homeostasis and cellular senescence caused by Col11a1-HIF1α-mediated glycolysis-OXPHOS shift in chondrocytes. Genetically and biologically inspired, an intra-articular injection therapy was fabricated to prevent cartilage degeneration with Col11a1-OE SMSC organoids. Col11a1-OE organoids ameliorated cartilage degeneration in DDH mice via regulating cellular senescence by up-regulated Col11a1/HIF1α-mediated glycolysis in chondrocytes.

Nerve Growth Factor-Preconditioned Mesenchymal Stem Cell-Derived Exosome-Functionalized 3D-Printed Hierarchical Porous Scaffolds with Neuro-Promotive Properties for Enhancing Innervated Bone Regeneration.

The essential role of the neural network in enhancing bone regeneration has often been overlooked in biomaterial design, leading to delayed or compromised bone healing. Engineered mesenchymal stem cells (MSCs)-derived exosomes are becoming increasingly recognized as potent cell-free agents for manipulating cellular behavior and improving therapeutic effectiveness. Herein, MSCs are stimulated with nerve growth factor (NGF) to regulate exosomal cargoes to improve neuro-promotive potential and facilitate innervated bone regeneration. In vitro cell experiments showed that the NGF-stimulated MSCs-derived exosomes (N-Exos) obviously improved the cellular function and neurotrophic effects of the neural cells, and consequently, the osteogenic potential of the osteo-reparative cells. Bioinformatic analysis by miRNA sequencing and pathway enrichment revealed that the beneficial effects of N-Exos may partly be ascribed to the NGF-elicited multicomponent exosomal miRNAs and the subsequent regulation and activation of the MAPK and PI3K-Akt signaling pathways. On this basis, N-Exos were delivered on the micropores of the 3D-printed hierarchical porous scaffold to accomplish the sustained release profile and extended bioavailability. In a rat model with a distal femoral defect, the N-Exos-functionalized hierarchical porous scaffold significantly induced neurovascular structure formation and innervated bone regeneration. This study provided a feasible strategy to modulate the functional cargoes of MSCs-derived exosomes to acquire desirable neuro-promotive and osteogenic potential. Furthermore, the developed N-Exos-functionalized hierarchical porous scaffold may represent a promising neurovascular-promotive bone reparative scaffold for clinical translation.

An osteosarcoma-on-a-chip model for studying osteosarcoma matrix-cell interactions and drug responses.

Marrow niches in osteosarcoma (OS) are a specialized microenvironment that is essential for the maintenance and regulation of OS cells. However, existing animal xenograft models are plagued by variability, complexity, and high cost. Herein, we used a decellularized osteosarcoma extracellular matrix (dOsEM) loaded with extracellular vesicles from human bone marrow-derived stem cells (hBMSC-EVs) and OS cells as a bioink to construct a micro-osteosarcoma (micro-OS) through 3D printing. The micro-OS was further combined with a microfluidic system to develop into an OS-on-a-chip (OOC) with a built-in recirculating perfusion system. The OOC system successfully integrated bone marrow niches, cell‒cell and cell-matrix crosstalk, and circulation, allowing a more accurate representation of OS characteristics in vivo. Moreover, the OOC system may serve as a valuable research platform for studying OS biological mechanisms compared with traditional xenograft models and is expected to enable precise and rapid evaluation and consequently more effective and comprehensive treatments for OS.

Detection of lineage-reprogramming efficiency of tumor cells in a 3D-printed liver-on-a-chip model.

Background: The liver metastasis accompanied with the loss of liver function is one of the most common complications in patients with triple-negative breast cancers (TNBC). Lineage reprogramming, as a technique direct inducing the functional cell types from one lineage to another lineage without passing through an intermediate pluripotent stage, is promising in changing cell fates and overcoming the limitations of primary cells. However, most reprogramming techniques are derived from human fibroblasts, and whether cancer cells can be reversed into hepatocytes remains elusive. Methods: Herein, we simplify preparation of reprogramming reagents by expressing six transcriptional factors (HNF4A, FOXA2, FOXA3, ATF5, PROX1, and HNF1) from two lentiviral vectors, each expressing three factors. Then the virus was transduced into MDA-MB-231 cells to generated human induced hepatocyte-like cells (hiHeps) and single-cell sequencing was used to analyze the fate for the cells after reprogramming. Furthermore, we constructed a Liver-on-a-chip (LOC) model by bioprinting the Gelatin Methacryloyl hydrogel loaded with hepatocyte extracellular vesicles (GelMA-EV) bioink onto the microfluidic chip to assess the metastasis behavior of the reprogrammed TNBC cells under the 3D liver microenvironment in vitro. Results: The combination of the genes HNF4A, FOXA2, FOXA3, ATF5, PROX1 and HNF1A could reprogram MDA-MB-231 tumor cells into human-induced hepatocytes (hiHeps), limiting metastasis of these cells. Single-cell sequencing analysis showed that the oncogenes were significantly inhibited while the liver-specific genes were activated after lineage reprogramming. Finally, the constructed LOC model showed that the hepatic phenotypes of the reprogrammed cells could be observed, and the metastasis of embedded cancer cells could be inhibited under the liver microenvironment. Conclusion: Our findings demonstrate that reprogramming could be a promising method to produce hepatocytes and treat TNBC liver metastasis. And the LOC model could intimate the 3D liver microenvironment and assess the behavior of the reprogrammed TNBC cells.

Photocurable 3D-printed PMBG/TCP biphasic scaffold mimicking vasculature for bone regeneration.

Mesoporous bioglass (MBG) with excellent osteointegration, osteoinduction, and biodegradability is a promising material for bone regeneration. However, its clinical application is hindered by complex processing and a lack of personalization, low mechanical strength, and uncontrollable degradation rate. In this study, we developed a double-bond-functionalized photocurable mesoporous bioglass (PMBG) sol that enabled ultrafast photopolymerization within 5 s. By further integrating nanosized tricalcium phosphate (TCP) particles through three-dimensional (3D) printing technology, we fabricated personalized and highly porous PMBG/TCP biphasic scaffolds. The mechanical properties and degradation behavior of the scaffolds were regulated by varying the amount of TCP doping. In vitro and in vivo experiments verified that PMBG/TCP scaffolds slowly released SiO44- and Ca2+, forming a vascularized bone regeneration microenvironment within the fully interconnected pore channels of the scaffold. This microenvironment promoted angiogenesis and accelerated bone tissue regeneration. Overall, this work demonstrates the solution to the problem of complex processing and lack of personalization in bioglass scaffolds, and the developed PMBG/TCP biphasic scaffold is an ideal material for bone regeneration applications with broad clinical prospects.

Swelling compensation of engineered vasculature fabricated by additive manufacturing and sacrifice-based technique using thermoresponsive hydrogel.

Engineered vasculature is widely employed to maintain the cell viability within in vitro tissues. A variety of fabrication techniques for engineered vasculature have been explored, with combination of additive manufacturing with a sacrifice-based technique being the most common approach. However, the size deformation of vasculature caused by the swelling of sacrificial materials remains unaddressed. In this study, Pluronic F-127 (PF-127), the most widely used sacrificial material, was employed to study the deformation of the vasculature. Then, a thermoresponsive hydrogel comprising poly(N-isopropylacrylamide) (PNIPAM) and gelatin methacrylate (GelMA) was used to induce volume shrinkage at 37°C to compensate for the deformation of vasculature caused by the swelling of a three-dimensional (3D)-printed sacrificial template, and to generate vasculature of a smaller size than that after deformation. Our results showed that the vasculature diameter increased after the sacrificial template was removed, whereas it decreased to the designed diameter after the volume shrinkage. Human umbilical vein endothelial cells (HUVECs) formed an endothelial monolayer in the engineered vasculature. Osteosarcoma cells (OCs) were loaded into a hierarchical vasculature within the thermoresponsive hydrogel to investigate the interaction between HUVECs and OCs. New blood vessel infiltration was observed within the lumen of the engineered vasculature after in vivo subcutaneous implantation for 4 weeks. In addition, engineered vasculature was implanted in a rat ischemia model to further study the function of engineered vasculature for blood vessel infiltration. This study presents a small method aiming to accurately create engineered vasculature by additive manufacturing and a sacrificebased technique.

A highly generalized classifier for osteoporosis radiography based on multiscale fractal, lacunarity, and entropy distributions.

Background: Osteoporosis is a common degenerative disease with high incidence among aging populations. However, in regular radiographic diagnostics, asymptomatic osteoporosis is often overlooked and does not include tests for bone mineral density or bone trabecular condition. Therefore, we proposed a highly generalized classifier for osteoporosis radiography based on the multiscale fractal, lacunarity, and entropy distributions. Methods: We collected a total of 104 radiographs (92 for training and 12 for testing) of lumbar spine L4 and divided them into three groups (normal, osteopenia, and osteoporosis). In parallel, 174 radiographs (116 for training and 58 for testing) of calcaneus from health and osteoporotic fracture groups were collected. The texture feature data of all the radiographs were pulled out and analyzed. The Davies-Bouldin index was applied to optimize hyperparameters of feature counting. Neighborhood component analysis was performed to reduce feature dimension and increase generalization. A support vector machine classifier was trained with only the most effective six features for each binary classification scenario. The accuracy and sensitivity performance were estimated by calculating the area under the curve. Results: Interpretable feature trends of osteoporotic pathological changes were depicted. On the spine test dataset, the accuracy and sensitivity of binary classifiers were 0.851 (95% CI: 0.730-0.922), 0.813 (95% CI: 0.718-0.878), and 0.936 (95% CI: 0.826-1) for osteoporosis diagnosis; 0.721 (95% CI: 0.578-0.824), 0.675 (95% CI: 0.563-0.772), and 0.774 (95% CI: 0.635-0.878) for osteopenia diagnosis; and 0.935 (95% CI: 0.830-0.968), 0.928 (95% CI: 0.863-0.963), and 0.910 (95% CI: 0.746-1) for osteoporosis diagnosis from osteopenia. On the calcaneus test dataset, they were 0.767 (95% CI: 0.629-0.879), 0.672 (95% CI: 0.545-0.793), and 0.790 (95% CI: 0.621-0.923) for osteoporosis diagnosis. Conclusion: This method showed the capacity of resisting disturbance on lateral spine radiographs and high generalization on the calcaneus dataset. Pixel-wise texture features not only helped to understand osteoporosis on radiographs better but also shed new light on computer-aided osteopenia and osteoporosis diagnosis.

A Retrospective Comparative Study of Endoscopic Treatment of Gastrocnemius Contracture using the Modified Soft Tissue Release Kit.

Background and Objectives: This study aimed to evaluate the effectiveness and safety of endoscopic gastrocnemius recession using the self-developed Modified Soft Tissue Release Kit. Materials and Methods: This retrospective review followed up 22 patients (34 feet) who underwent endoscopic surgery and 20 patients (30 feet) who received open surgery between January 2020 and January 2022. The American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score and the maximum ankle dorsiflexion angle were evaluated preoperatively and at the last follow-up. Postoperative complications were recorded. Patient satisfaction was surveyed at the last follow-up. The comparison between quantitative data was analyzed with the Wilcoxon signed-rank test. The comparison between qualitative data was analyzed with the chi-square test. Results: There was no significant difference in the baseline characteristics between the two groups. The AOFAS score in the endoscopic group increased from 50 (18) points preoperatively to 90 (13) points at the last follow-up; the maximum ankle dorsiflexion angle increased from -7.7 (2.8) degrees to 10.6 (3.6) degrees. The AOFAS score in the open group improved from 47 (15) points preoperatively to 90 (18) points at the last follow-up; the maximum ankle dorsiflexion angle increased from -7.6 (4.0) degrees to 10.7 (3.3) degrees. The change values of the AOFAS scores in the endoscopic and open groups were 39 (15) and 40.5 (11) points, respectively, and there was no significant difference between them. The change values of the maximum ankle dorsiflexion angles in the endoscopic and open groups were 19.5 (4.3) and 19.1 (4.9) degrees, respectively, and there was no significant difference between them. There were no complications, such as sural nerve injury, in both groups. There was no significant difference between the two groups in satisfaction with the surgical outcome. Conclusions: Endoscopic gastrocnemius recession using the Modified Soft Tissue Release Kit can significantly improve the foot function with significant mid-term efficacy and high safety.

Regeneration of Humeral Head Using a 3D Bioprinted Anisotropic Scaffold with Dual Modulation of Endochondral Ossification.

Tissue engineering is theoretically thought to be a promising method for the reconstruction of biological joints, and thus, offers a potential treatment alternative for advanced osteoarthritis. However, to date, no significant progress is made in the regeneration of large biological joints. In the current study, a biomimetic scaffold for rabbit humeral head regeneration consisting of heterogeneous porous architecture, various bioinks, and different hard supporting materials in the cartilage and bone regions is designed and fabricated in one step using 3D bioprinting technology. Furthermore, orchestrated dynamic mechanical stimulus combined with different biochemical cues (parathyroid hormone [PTH] and chemical component hydroxyapatite [HA] in the outer and inner region, respectively) are used for dual regulation of endochondral ossification. Specifically, dynamic mechanical stimulus combined with growth factor PTH in the outer region inhibits endochondral ossification and results in cartilage regeneration, whereas dynamic mechanical stimulus combined with HA in the inner region promotes endochondral ossification and results in efficient subchondral bone regeneration. The strategy established in this study with the dual modulation of endochondral ossification for 3D bioprinted anisotropic scaffolds represents a versatile and scalable approach for repairing large joints.

A Retrospective Clinical Study of Endoscopic Treatment of Carpal Tunnel Syndrome using the Modified Soft Tissue Release kit.

OBJECTIVE: Carpal tunnel syndrome (CTS) is the most common peripheral entrapment neuropathy, and endoscopic carpal tunnel release (ECTR) is one of the minimally invasive procedures for the treatment of CTS. Based on the shortcomings of ECTR, we designed the "Modified Soft Tissue Release Kit" to assist the endoscopic operation. This study aimed to evaluate the effectiveness and safety of endoscopic treatment of CTS using this kit. METHODS: This retrospective review included 57 patients (86 wrists) who underwent ECTR using the "Modified Soft Tissue Release Kit" at our department between January 2017 and August 2019. Three scale scores (i.e., Quick-Disabilities of the Arm, Shoulder, and Hand [QDASH]; Boston Carpal Tunnel Syndrome Questionnaire [BCTSQ]: symptom severity [BCTSQ-SS] and functional status [BCTSQ-FS]) were recorded to assess hand function and symptoms preoperatively, 1 month postoperatively, 3 months postoperatively, and at the last follow-up. We also asked patients to answer a satisfaction question during follow-up. Pre- and post-operation scores were compared using paired Wilcoxon signed-rank test. Spearman's rank-order correlation was used to evaluate the relationship between scale scores and patient satisfaction. RESULTS: A total of 55 patients (83 wrists) were followed up, with an average follow-up of 27.2 ± 9.3 months. The median preoperative QDASH score was 45.5; the scores at 1 month postoperatively, 3 months postoperatively, and the last follow-up were 4.5, 0, and 0, respectively, with a significant decrease noted compared with the preoperative scores (P < 0.001). The median preoperative BCTSQ-SS and BCTSQ-FS scores were 3.3 and 2.8, respectively; the scores at 1 month postoperatively, 3 months postoperatively, and the last follow-up were 1.2, 1.0, and 1.0, and 1.1, 1.0, and 1.0, respectively, all of which decreased significantly compared with the preoperative scores (P < 0.001). The incidence of nerve injury was 0. The incidence of pillar pain was 0 at the last follow-up. One patient showed no improvement in hand symptoms and function postoperatively, and two patients showed long-term recurrence despite postoperative symptom remission. Approximately 94.5% (52/55) of the patients were satisfied or very satisfied with the outcome. CONCLUSIONS: ECTR with the "Modified Soft Tissue Release Kit" can significantly relieve symptoms and improve function in patients with CTS, with significant short- and mid-term efficacy and high safety.

A retrospective study of the mid-term efficacy of full-endoscopic annulus fibrosus suture following lumbar discectomy.

Aims: Full-endoscopic discectomy is associated with a high risk of disc reherniation due to the poor mechanical strength of the annulus fibrosus after scar healing. It is technically difficult to place a full-endoscopic annulus fibrosus suture. We designed an annulus fibrosus suture device that can be used to suture annulus defects under microendoscopy. The present study investigated the safety and feasibility of this technology. Patients and Methods: We retrospectively analyzed the outcomes of patients who underwent surgical treatment for lumbar disc herniation (LDH) from January 2018 to October 2020. We compared 40 patients with LDH treated with full-endoscopic annulus fibrosus suture following lumbar discectomy (LD + AFS group) with 42 patients treated with lumbar discectomy alone (LD group) regarding demographic data, symptoms, and recurrence and reoperation rates. Lumbar MRI and CT were performed 3 and 12 months. A 10-point visual analog scale (VAS) and the Oswestry Disability Index (ODI) was used to evaluate pain and the lumbar spine function. Results: The cohort comprised 82 patients, including 40 patients in the LD + AFS group and 42 in the LD group. All operations were successfully completed without serious complications. Reherniation occurred in no patients in the LD + AFS group and three patients in the LD group. The VAS scores for lumbar and leg pain and ODI score were significantly improved postoperatively (p < 0.05). Conclusion: Compared with conventional lumbar discectomy, full-endoscopic annulus fibrosus suture following full-endoscopic lumbar discectomy is a safe and effective minimally invasive technique that reduces the LDH recurrence rate.

Outcomes of V-cut Osteotomy on the First Metatarsal Head Combined with Fixation in Mortise-shaped Bone Groove-Plasty and Akin Osteotomy on the First Toe for Hallux Valgus Correction.

OBJECTIVE: Hallux valgus (HV) is a common foot deformity, and recurrence is one of the most serious complications after HV correction. As a result, the surgical technique with a lower recurrence rate is a dream. The purpose of the article should be to observe the correction effect of hallux valgus using a novel "V-cut" osteotomy on the first metatarsal head combined with fixation in mortise-shaped bone groove-plasty technique. METHODS: Twenty-three consecutive patients (40 feet) with HV were included from March 2019 to May 2020, who were all treated using single screw fixation with V-cut osteotomy on the first metatarsal head combined with mortise-shaped metatarsal bone groove-plasty and Akin osteotomy on the first toe for hallux valgus correction. With a mean follow-up time of 21.7 months, the visual analogue scale (VAS) score and American Orthopedic Foot and Ankle Society (AOFAS) forefoot score and the changes of the hallux valgus angle (HVA), intermetatarsal angle (IMA) and distal metatarsal articular angle (DMAA) were evaluated during the clinical follow-up. The paired t test was used for analytical statistics. RESULTS: The VAS score improved from 6.78 ± 1.74 to 1.87 ± 1.45 and the AOFAS score improved from 53.9 ± 12.3 preoperatively to 94.7 ± 6.8 in the latest follow-up postoperatively (P < 0.01). Besides, the HVA improved from 30.0 ± 6.1° to 5.7 ± 2.8° (P < 0.01); the IMA changed from 13.1 ± 2.8° into 3.3 ± 1.6° (P < 0.01); and the DMAA ameliorated from 27.0 ± 8.4° to 5.9 ± 3.5° (P < 0.01). Only five toes had slight numbness and stiffness in early postoperative period, and these symptoms disappeared completely at 6 months after the surgery. Only one foot was corrected to excess. One screw stern protruding beneath the skin happened, which needed secondary screw removal under local anesthesia. CONCLUSIONS: Single screw fixation with V-cut osteotomy on the first metatarsal head combined with fixation in mortise-shaped metatarsal bone groove-plasty and Akin osteotomy on the first toe is an effective way with low recurrence rate for HV correction.

Chondrogenic primed extracellular vesicles activate miR-455/SOX11/FOXO axis for cartilage regeneration and osteoarthritis treatment.

Osteoarthritis (OA) is the leading cause of disability worldwide. Considerable progress has been made using stem-cell-derived therapy. Increasing evidence has demonstrated that the therapeutic effects of BMSCs in chondrogenesis could be attributed to the secreted small extracellular vesicles (sEVs). Herein, we investigated the feasibility of applying engineered EVs with chondrogenic priming as a biomimetic tool in chondrogenesis. We demonstrated that EVs derived from TGFß3-preconditioned BMSCs presented enriched specific miRNAs that could be transferred to native BMSCs to promote chondrogenesis. In addition, We found that EVs derived from TGFß3-preconditioned BMSCs rich in miR-455 promoted OA alleviation and cartilage regeneration by activating the SOX11/FOXO signaling pathway. Moreover, the designed T3-EV hydrogel showed great potential in cartilage defect treatment. Our findings provide new means to apply biosafe engineered EVs from chondrogenic primed-BMSCs for cartilage repair and OA treatment, expanding the understanding of chondrogenesis and OA development modulated by EV-miRNAs in vivo.

Application of 3D printing individualized guide plates in percutaneous needle biopsy of acetabular tumors.

Objective: The objective of the study was to investigate the effectiveness of applying the individualized guide plate which is based on digital image processing and 3D printing technology to percutaneous needle biopsy of periacetabular tumor. Methods: From July 2017 to August 2019, 11 patients (5 males and 6 females, aged 13-70 years, mean 42.3 years) with acetabular tumors diagnosed by needle biopsy in our hospital were enrolled in this retrospective study. Preoperative CT and MRI enhancement examination were performed routinely, and the DICOM data were collected and imported into Medraw Print software. According to the specific anatomical morphology of acetabula, this study adopted the reverse calculation and direct design to print the individualized puncture guide plate using 3D printing technology. The puncture point and sampling approaches were determined by the guide plate morphology and the "double guide-hole and slideable groove" design. First, we evaluated the fitness of the 3D guide plate to the local anatomical structure, its assisted-puncture accuracy was estimated by imaging examinations, and postoperative complications were recorded. The accuracy of the needle biopsy pathological result was estimated with reference to that of the tumor resection. Results: Our results showed that the 3D printing individualized guide plate matched the patients' pelvic skin well, the puncture approach was consistent with the preoperative design, and no significant anatomical injuries including vascular and neural complications occurred after surgery. Nine patients' (90%) biopsy results were consistent with their postoperative pathological results, and one patient gave up the tumor resection. Conclusion: Based on digital image processing and 3D printing technology, the individualized guide plate can be used to guide the needle biopsy of acetabular tumors which makes the operation simpler and more precise.

Interactive effects of cerium and copper to tune the microstructure of silicocarnotite bioceramics towards enhanced bioactivity and good biosafety.

Endowing biomaterials with functional elements enhances their biological properties effectively. However, improving bioactivity and biosafety simultaneously is still highly desirable. Herein, cerium (Ce) and copper (Cu) are incorporated into silicocarnotite (CPS) to modulate the constitution and microstructure for degradability, bioactivity and biosafety regulation. Our results demonstrated that introducing Ce suppressed scaffold degradation, while, co-incorporation of both Ce and Cu accelerated degradability. Osteogenic effect of CPS in vitro was promoted by Ce and optimized by Cu, and Ce-induced angiogenic inhibition could be mitigated by cell coculture method and reversed by Ce-Cu co-incorporation. Ce enhanced osteogenic and angiogenic properties of CPS in a dose-dependent manner in vivo, and Cu-Ce coexistence exhibited optimal bioactivity and satisfactory biosafety. This work demonstrated that coculture in vitro was more appropriately reflecting the behavior of implanted biomaterials in vivo. Interactive effects of multi-metal elements were promising to enhance bioactivity and biosafety concurrently. The present work provided a promising biomaterial for bone repair and regeneration, and offered a comprehensive strategy to design new biomaterials which aimed at adjustable degradation behavior, and enhanced bioactivity and biosafety.

Three-dimensional printing bilayer membranous nanofiber scaffold for inhibiting scar hyperplasia of skin.

Hypertrophic scar (HS) is the manifestation of pathological wound healing, which affects the beauty of patients, and even affects the normal physical functions of patients. We aimed to develop a 3D printing layer membranous nanofiber scaffold similar to skin structure. Among them, poly (lactic-co-glycolic acid) copolymer (PLGA) nanofibers were used as the "epidermis" layer above, and a decellular dermis matrix (dECM) nanofiber scaffold was used as the "dermis" layer below. In vitro, experimental results showed that PLGA and dECM nanofiber scaffolds had good biocompatibility. In vivo experiments showed that BLM nanofiber scaffolds could inhibit collagen fiber deposition and angiogenesis, to inhibit the formation of hypertrophic scars. This study shows a simple and effective method for preventing and inhibiting the formation of hypertrophic scars.

Modified Biodegradation Behavior Induced Beneficial Microenvironments for Bone Regeneration by Low Addition of Gadolinium in Zinc.

Zinc (Zn) shows a great potential as a biodegradable material for bone implants after a decade of systematic research and development. However, uncontrollable biodegradation behavior and biphasic dose-response prevent Zn from fulfilling its essential role in facilitating bone regeneration. In this study, the low addition of gadolinium (Gd) modifies the intrinsic microstructure of Zn in terms of grain size distribution, grain boundary misorientation, and texture. Adding Gd refines grain size distribution and creates a stronger basal plane texture in Zn, consequently, changing the current density distribution and reducing the anode dissolution rate during corrosion. As a result, uniform degradation is more predominant in Zn-0.4Gd alloy implant, in comparison to localized degradation in pure Zn implant in bone environments. The modified biodegradation behavior of the Zn-0.4Gd alloy implant induces significantly better new bone formation and osseointegration compared to the pure Zn implant. Therefore, Gd with trace amounts is able to tune the degradation behavior and improve the performance of Zn-based implants in promoting bone regeneration.

Distal Humeral Trochlear Geometry Associated With the Spatial Variation of the Dynamic Elbow Flexion Axis.

Background: The complexity of the spatial dynamic flexion axis (DFA) of the elbow joint makes the elbow prosthesis design and humeral component alignment challenging. This study aimed to 1) investigate the variations of the spatial DFA during elbow flexion and 2) investigate the relationship between the distal humeral trochlear geometry and the in vivo spatial variation of the DFA. Methods: Ten healthy subjects participated in this study. Each subject performed a full elbow extension to maximum flexion with hand supination under dual fluoroscopic imaging system (DFIS) surveillance. The 2D fluoroscopic images and the 3D bone models were registered to analyze the in vivo elbow kinematics and DFAs. The spatial DFA positions were defined as inclination with the medial and lateral epicondyle axes (MLA) in the transverse and coronal planes. The range of the DFA positions was also investigated during different flexion phases. The Spearman correlation method was used to analyze the relationship between the distal humeral trochlear's morphological parameters and the position of DFAs during different flexion phases. Results: The pathway of the DFAs showed an irregular pattern and presented individual features. The medial trochlear depth (MTD) (r = 0.68, p = 0.03) was positively correlated with the range of the DFA position (2.8° ± 1.9°) in the coronal plane from full extension to 30° of flexion. Lateral trochlear height (LTH) (r = -0.64, p = 0.04) was negatively correlated with the DFA position (-1.4° ± 3.3°) in the transverse plane from 30° to 60° of flexion. A significant correlation was found between LTH with the DFA position in the coronal (r = -0.77, p = 0.01) and transverse planes (r = -0.76, p = 0.01) from 60° to 90° of flexion. Conclusion: This study showed that the pathway of the dynamic flexion axis has an individual pattern. The medial and lateral trochlear sizes were the key parameters that might affect the elbow joint flexion function. When recovering complex distal humeral fractures or considering the implant design of total elbow arthroplasty, surgeons should pay more attention to the medial and lateral trochlea's geometry, which may help restore normal elbow kinematics.