Decellularized Brain Extracellular Matrix Hydrogel Aids the Formation of Human Spinal-Cord Organoids Recapitulating the Complex Three-Dimensional Organization.

The intricate electrophysiological functions and anatomical structures of spinal cord tissue render the establishment of in vitro models for spinal cord-related diseases highly challenging. Currently, both in vivo and in vitro models for spinal cord-related diseases are still underdeveloped, complicating the exploration and development of effective therapeutic drugs or strategies. Organoids cultured from human induced pluripotent stem cells (hiPSCs) hold promise as suitable in vitro models for spinal cord-related diseases. However, the cultivation of spinal cord organoids predominantly relies on Matrigel, a matrix derived from murine sarcoma tissue. Tissue-specific extracellular matrices are key drivers of complex organ development, thus underscoring the urgent need to research safer and more physiologically relevant organoid culture materials. Herein, we have prepared a rat decellularized brain extracellular matrix hydrogel (DBECMH), which supports the formation of hiPSC-derived spinal cord organoids. Compared with Matrigel, organoids cultured in DBECMH exhibited higher expression levels of markers from multiple compartments of the natural spinal cord, facilitating the development and maturation of spinal cord organoid tissues. Our study suggests that DBECMH holds potential to replace Matrigel as the standard culture medium for human spinal cord organoids, thereby advancing the development of spinal cord organoid culture protocols and their application in in vitro modeling of spinal cord-related diseases.

Human Placenta Decellularized Extracellular Matrix Hydrogel Promotes the Generation of Human Spinal Cord Organoids with Dorsoventral Organization from Human Induced Pluripotent Stem Cells.

Spinal cord organoids are of significant value in the research of spinal cord-related diseases by simulating disease states, thereby facilitating the development of novel therapies. However, the complexity of spinal cord structure and physiological functions, along with the lack of human-derived inducing components, presents challenges in the in vitro construction of human spinal cord organoids. Here, we introduce a novel human decellularized placenta-derived extracellular matrix hydrogel (DPECMH) and, combined with a new induction protocol, successfully construct human spinal cord organoids. The human placenta-sourced decellularized extracellular matrix (dECM), verified through hematoxylin and eosin staining, DNA quantification, and immunofluorescence staining, retained essential ECM components such as elastin, fibronectin, type I collagen, laminin, and so forth. The temperature-sensitive hydrogel made from human placenta dECM demonstrated good biocompatibility and promoted the differentiation of human induced pluripotent stem cell (hiPSCs)-derived spinal cord organoids into neurons. It displayed enhanced expression of laminar markers in comparison to Matrigel and showed higher expression of laminar markers compared to Matrigel, accelerating the maturation process of spinal cord organoids and demonstrating its potential as an organoid culture substrate. DPECMH has the potential to replace Matrigel as the standard additive for human spinal cord organoids, thus advancing the development of spinal cord organoid culture protocols and their application in the in vitro modeling of spinal cord-related diseases.

Electrospun PCL Nerve Conduit Filled with GelMA Gel for CNTF and IGF-1 Delivery in Promoting Sciatic Nerve Regeneration in Rat.

Neural tissue engineering is an essential strategy to repair long-segment peripheral nerve defects. Modification of the nerve conduit is an effective way to improve the local microenvironment of the injury site and facilitate nerve regeneration. However, the concurrent release of multiple growth cues that regulate the activity of Schwann cells and neurons remains a challenge. The present study involved the fabrication of a composite hydrogel, specifically methacrylate-anhydride gelatin-ciliary neurotrophic factor/insulin-like growth factor-1 (GelMA-CNTF/IGF-1), with the aim of providing a sustained release of CNTF and IGF-1. The GelMA-CNTF/IGF-1 hydrogels exhibited a swelling rate of 10.2% following a 24 h incubation in vitro. In vitro, GelMA hydrogels demonstrated a high degree of efficiency in the sustained release of CNTF and IGF-1 proteins, with a release rate of 85.9% for CNTF and 90.9% for IGF-1 shown at day 28. In addition, the GelMA-CNTF/IGF-1 composite hydrogel promoted the proliferation of Schwann cells and the production of nerve growth factor (NGF), connective tissue growth factor (CTGF), fibronectin, and laminin and also considerably promoted the axonal growth of neurons. Furthermore, GelMA-CNTF/IGF-1 hydrogels were loaded into PCL electrospun nerve conduits to repair 15 mm sciatic nerve defects in rats. In vivo studies indicated that PCL-GelMA-CNTF/IGF-1 could efficiently accelerate the regeneration of the rat sciatic nerve, promote the formation of the myelin sheath of new axons, promote the electrophysiological function of regenerated nerves, and eventually improve the recovery of motor function in rats. Overall, the PCL-GelMA-CNTF/IGF-1 scaffold presents an attractive new approach for generating an optimal therapeutic alternative for peripheral nerve restoration.

Incorporation of synthetic water-soluble curcumin polymeric drug within calcium phosphate cements for bone defect repairing.

Modified macroporous structures and active osteogenic substances are necessary to overcome the limited bone regeneration capacity and low degradability of self-curing calcium phosphate cement (CPC). Curcumin (CUR), which possesses strong osteogenic activity and poor aqueous solubility/bioavailability, esterifies the side chains in hyaluronic acid (HA) to form a water-soluble CUR-HA macromolecule. In this study, we incorporated the CUR-HA and glucose microparticles (GMPs) into the CPC powder to fabricate the CUR-HA/GMP/CPC composite, which not only retained the good injectability and mechanical strength of bone cements, but also significantly increased the cement porosity and sustained release property of CUR-HA in vitro. CUR-HA incorporation greatly improved the differentiation ability of bone marrow mesenchymal stem cells (BMSCs) to osteoblasts by activating the RUNX family transcription factor 2/fibroblast growth factor 18 (RUNX2/FGF18) signaling pathway, increasing the expression of osteocalcin and enhancing the alkaline phosphatase activity. In addition, in vivo implantation of CUR-HA/GMP/CPC into femoral condyle defects dramatically accelerated the degradation rate of cement and boosted local vascularization and osteopontin protein expression, and consequently promoted rapid bone regeneration. Therefore, macroporous CPC based composite cement with CUR-HA shows a remarkable ability to repair bone defects and is a promising translational application of modified CPC in clinical practice.

Supramolecular Hydrogel Microspheres of Platelet-Derived Growth Factor Mimetic Peptide Promote Recovery from Spinal Cord Injury.

Neural stem cells (NSCs) are considered to be prospective replacements for neuronal cell loss as a result of spinal cord injury (SCI). However, the survival and neuronal differentiation of NSCs are strongly affected by the unfavorable microenvironment induced by SCI, which critically impairs their therapeutic ability to treat SCI. Herein, a strategy to fabricate PDGF-MP hydrogel (PDGF-MPH) microspheres (PDGF-MPHM) instead of bulk hydrogels is proposed to dramatically enhance the efficiency of platelet-derived growth factor mimetic peptide (PDGF-MP) in activating its receptor. PDGF-MPHM were fabricated by a piezoelectric ceramic-driven thermal electrospray device, had an average size of 9 µm, and also had the ability to activate the PDGFRß of NSCs more effectively than PDGF-MPH. In vitro, PDGF-MPHM exerted strong neuroprotective effects by maintaining the proliferation and inhibiting the apoptosis of NSCs in the presence of myelin extracts. In vivo, PDGF-MPHM inhibited M1 macrophage infiltration and extrinsic or intrinsic cells apoptosis on the seventh day after SCI. Eight weeks after SCI, the T10 SCI treatment results showed that PDGF-MPHM + NSCs significantly promoted the survival of NSCs and neuronal differentiation, reduced lesion size, and considerably improved motor function recovery in SCI rats by stimulating axonal regeneration, synapse formation, and angiogenesis in comparison with the NSCs graft group. Therefore, our findings provide insights into the ability of PDGF-MPHM to be a promising therapeutic agent for SCI repair.

Thoracic Jia-Ji electro-acupuncture mitigates low skeletal muscle atrophy and improves motor function recovery following thoracic spinal cord injury in rats.

OBJECTIVES: The goal of this study was to determine whether electro-acupuncture (EA) stimulation might protect the motor endplate, minimize muscle atrophy in the hind limbs, and enhance functional recovery of rats with spinal cord injury (SCI). METHODS: Sprague-Dawley adult female rats (n = 30) were randomly assigned into Sham, SCI, and EA + SCI groups (n = 10 each). Rats in the Sham and SCI groups were bound in prone position only for 30 min, and rats in the EA + SCI group were treated with electro-acupuncture. The EA was conducted from the first day after surgery, lasted for 30 mins, once every day for 28 consecutive days. RESULTS: EA significantly prevented motor endplate degeneration, improved electrophysiological function, and ameliorated hindlimb muscle atrophy after SCI. Meanwhile, EA upregulated Tuj-1 expression, downregulated GFAP expression, and reduced glial scar formation. Additionally, after 4 weeks of EA treatment, the serum of SCI rats exhibited a reduced inflammatory response. CONCLUSION: These findings suggest that EA can preserve the motor endplate and reduce muscular atrophy. In addition, EA has been shown to improve the function of upper and lower neurons, reduce glial scar formation, suppress systemic inflammation, and improve axon regeneration.

A functionalized self-assembling peptide containing E7 and YIGSR sequences enhances neuronal differentiation of spermatogonial stem cells on aligned PCL fibers for spinal cord injury repair.

Background: Spinal cord injury (SCI) induces neuronal death and disrupts the nerve fiber bundles, which leads to partial or complete sensorimotor function loss of the limbs. Transplantation of exogenous neurons derived from stem cells to the lesion site becomes a new neurorestorative strategy for SCI treatment. Spermatogonial stem cells (SSCs) can attain pluripotency features by converting to embryonic stem-like cells in vitro. However, differentiating SSCs into lineage-specific neurons is quite difficult and low efficiency. Methods: Immunofluorescence, immunohistochemistry, Western blotting, whole-cell patch clamp, and behavioral tests were performed to verify that self-assembled hydrogels could improve the directional differentiation efficiency of SSCs and the feasibility of SSC-derived neurons in the treatment of spinal cord injury. Results: We developed a novel self-assembled peptide Nap-FFGEPLQLKMCDPGYIGSR (Nap-E7-YIGSR) coated with aligned electrospun PCL fibers to enhance neuronal differentiation of SSCs. The Nap-E7-YIGSR peptide could evenly self-assemble on the surface of PCL fibers, enhanced the materials's hydrophilicity, and improved the SSC affinity of PCL fibers through the stem cell adhesion peptide sequence EPLQLKM domain. In addition, Nap-E7-YIGSR could effectively induce SSC neuron differentiation by activating the integrin ß1/GSK3ß/ß-catenin signaling pathway. Moreover, implanting the induced neurons derived from SSCs into SCI lesion sites in rats resulted in the formation of new relay circuits, myelination, and synapse formation. Furthermore, SSC-derived neurons could survive and function in the spinal cord injury microenvironment, boosting the recovery of locomotion. Conclusion: The combination of the multifunctional peptide and aligned fibers can potentially trigger SSC differentiation to neurons, facilitating neuronal replacement therapy and promoting functional recovery after SCI.

In Vitro and In Vivo Evaluation of Injectable Strontium-Modified Calcium Phosphate Cement for Bone Defect Repair in Rats.

Calcium phosphate cement (CPC) has been widely studied, but its lack of osteoinductivity and inadequate mechanical properties limit its application, while strontium is able to promote bone formation and inhibit bone resorption. In this study, different proportions of tristrontium silicate were introduced to create a novel strontium-modified calcium phosphate cement (SMPC). The physicochemical properties of SMPC and CPC were compared, and the microstructures of the bone cements were characterized with scanning electron microscopy assays. Then, the effect of SMPC on cell proliferation and differentiation was examined. Furthermore, local inflammatory response and osteogenesis after SMPC implantation were also confirmed in the study. Finally, a rat model of isolated vertebral defects was used to test the biomechanical properties of the cements. The results showed that SMPC has better injectability and a shorter setting time than CPC. Meanwhile, the addition of tristrontium silicate promoted the mechanical strength of calcium phosphate cement, and the compressive strength of 5% SMPC increased to 6.00 ± 0.74 MPa. However, this promotion effect gradually diminished with an increase in tristrontium silicate, which was also found in the rat model of isolated vertebral defects. Furthermore, SMPC showed a more preferential role in promoting cell proliferation and differentiation compared to CPC. Neither SMPC nor CPC showed significant inflammatory responses in vivo. Histological staining suggested that SMPCs were significantly better than CPC in promoting new bone regeneration. Importantly, this osteogenesis effect of SMPC was positively correlated with the ratio of tristrontium silicate. In conclusion, 5% SMPC is a promising substitute material for bone repair with excellent physicochemical properties and biological activity.

Circular RNA circNRIP1 plays oncogenic roles in the progression of osteosarcoma.

Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents. Increasing evidence suggests that aberrant expression of circRNAs is associated with the occurrence and progression of many cancers. Here, we investigated the role of circNRIP1 in osteosarcoma and explored its possible underlying mechanisms. Three pairs of osteosarcoma tissues and adjacent normal tissues were applied to the detection of altered expression of circRNAs through circRNAs microarray. And the level of circNRIP1 expression was elevated in osteosarcoma tissues. Compared with that in adjacent normal tissue, circNRIP1 expression level was obviously elevated in 100 osteosarcoma tissues. Besides, circNRIP1 knockdown inhibited proliferation and migration, promoted apoptosis of osteosarcoma cells. Bioinformatic analysis demonstrated circNRIP1 contributed to FOXC2 expression by sponging miR-199a. Furthermore, METTL3 elevated circNRIP1 expression level via m6A modification. In short, METTL3-induced circNRIP1 exerted an oncogenic role in osteosarcoma by sponging miR-199a, which may provide new ideas for the treatment of osteosarcoma.

[Effects of calcium phosphate cement combined with hyaluronic acid/curcumin on the proliferation and osteogenesis of osteoblasts].

OBJECTIVE: After using hyaluronic acid (HA) to modify curcumin (CUR), the effects of calcium phosphate cement (CPC) combined with HA/CUR on the proliferation and osteogenesis of osteoblasts were investigated. METHODS: First, HA and CUR were esterified and covalently combined to prepare HA/CUR, and the characteristics were observed and the infrared spectrum was tested. Then, HA, CUR, and HA/CUR were mixed with CPC according to 5% ( W/ W) to prepare HA-CPC, CUR-CPC, and HA/CUR-CPC, respectively. Setting time detection, scanning electron microscope observation, injectable performance test, and compression strength test were conducted; and the CPC was used as a control. Osteoblasts were isolated and cultured from the skull of newborn Sprague Dawley rats, and the 2nd generation cells were cultured with the 4 types of bone cement, respectively. The effects of HA/CUR-CPC on the proliferation and osteogenesis of osteoblasts were estimated by the scanning electron microscopy observation, live/dead cell fluorescence staining, cell counting, osteopontin (OPN) immunofluorescence staining, alkaline phosphatase (ALP) staining,and alizarin red staining. RESULTS: Infrared spectroscopy test showed that HA and CUR successfully covalently combined. The HA/CUR-CPC group had no significant difference in initial setting time, final setting time, injectable rate, and compressive strength when compared with the other 3 groups ( P>0.05); scanning electron microscope observation showed that HA/CUR was scattered on CPC surface. After co-culture of bone cement and osteoblasts, scanning electron microscopy observation showed that the osteoblasts, which had normal morphology and the growth characteristics of osteoblasts, clustered and adhered to HA/CUR-CPC. There was no significant difference in cell survival rate between HA/CUR-CPC group and other groups ( P>0.05), and the number of cells significantly increased ( P<0.05); the degrees of OPN immunofluorescence staining, ALP staining, and alizarin red staining were stronger than other groups. CONCLUSION: HA/CUR-CPC has good biocompatibility and mechanical properties, which can promote the proliferation and osteogenesis of osteoblasts.

Reliability and application of the new morphological classification system for chronic symptomatic osteoporotic thoracolumbar fracture.

BACKGROUND: We propose a new classification system for chronic symptomatic osteoporotic thoracolumbar fracture (CSOTF) based on fracture morphology. Research on CSOTF has increased in recent years; however, the lack of a standard classification system has resulted in inconvenient communication, research, and treatment. Previous CSOTF classification studies exhibit different symptoms, with none being widely accepted. METHODS: Imaging data of 368 patients with CSOTF treated at our hospital from January 2010 to June 2017 were systematically analyzed to develop a classification system. Imaging examinations included dynamic radiography, computed tomography scans, and magnetic resonance imaging. Ten investigators methodically studied the classification system grading in 40 cases on two occasions, examined 1 month apart. Kappa coefficients (κ) were calculated to determine intraobserver and interobserver reliability. Based on the radiographic characteristics, the patients were divided into 5 types, and different treatments were suggested for each type. Clinical outcome evaluation included using the visual analog score (VAS), the Oswestry disability index (ODI), and the American Spinal Injury Association (ASIA) impairment scale. RESULTS: The new classification system for CSOTF was divided into types I-V according to whether the CSOTF exhibited dynamic instability, spinal stenosis or kyphosis deformity. Intra- and interobserver reliability were excellent for all types (κ = 0.83 and 0.85, respectively). The VAS score and ODI of each type were significantly improved at the final follow-up compared with those before surgery. In all patients with neurological impairment, the ASIA grading after surgery was significantly improved compared with that before surgery (P < 0.001). CONCLUSIONS: The new classification system for CSOTF demonstrated excellent reliability in this initial assessment. The treatment algorithm based on the classification can result in satisfactory improvement of clinical efficacy for the patients of CSOFT.

Positive feedback loop SP1/MIR17HG/miR-130a-3p promotes osteosarcoma proliferation and cisplatin resistance.

Long noncoding RNAs (lncRNAs) have been identified to be critical regulator in the osteosarcoma (OS) tumorigenesis. However, the role of lncRNA MIR17HG in the OS proliferation and chemotherapy resistance is still unclear. Here, this research aims to investigate the function of lncRNA MIR17HG in the OS proliferation and cisplatin resistance. Clinically, results revealed that higher MIR17HG expression was associated with shorter overall survival. Functional investigations indicated that MIR17HG promoted the proliferation, invasion and cisplatin resistance of OS cells in vitro, and the MIR17HG knockdown inhibited the growth in vivo. Mechanistically, MIR17HG targeted the miR-130a-3p/SP1 axis, moreover, transcription factor SP1 bind with the MIR17HG promoter region to promote its expression. Taken together, MIR17HG displays the tumor-promotive role in the progression of OS through SP1/MIR17HG/miR-130a-3p/SP1 feedback loop. Our findings might help us to offer novel therapeutic strategies for OS.

Application of transforaminal-lumbar interbody fusion technology combined with lesion clearance and chemotherapy via catheter for the treatment of spinal tuberculosis.

The aim of the present study was to analyze the clinical and radiological outcomes of active thoracolumbar spinal tuberculosis (TB) treated by application of transforaminal-lumbar interbody fusion technology combined with lesion clearance and chemotherapy via catheter (TCLC). Posterior debridement and indwelling catheterization in the lesion area were performed for direct injection of anti-TB drugs, so as to reduce the recurrence rate. The present prospective study comprised 26 patients with active thoracolumbar spinal TB who underwent TCLC at Hong Hui Hospital affiliated to Xi'an Jiaotong University (Xi'an, China). The kyphotic Cobb angle at presentation, after surgery and at the final follow-up were 22.7±9.8, 9.8±7.3 and 10.3±8.8°, respectively, with an average correction of 13.1±5.4° after surgery, and a loss of correction of 1.8±1.0° at the final follow-up. The rate of correction and loss of correction were 56.6 and 8.3%, respectively. At six months after the surgery, all abnormal erythrocyte sedimentation rates and C-reactive protein levels had returned to normal. The average time to union was ~5 months. All patients had bony union and improved neurological function, with their daily activity returning to normal. In conclusion, in the present study, application of TCLC for the treatment of spinal TB achieved satisfactory healing of lesions. The surgical treatment for spinal TB comprised the removal of the disease as far as possible, and the local administration of anti-TB chemotherapy to the lesion is key to successful treatment.

An innovative technique for osteoporotic vertebral compression fractures - vertebral osteotome with side-opening cannula.

OBJECTIVE: This study is to assess an innovative technique - a vertebral osteotome (VO) combined with side-opening injection cannula for percutaneous vertebroplasty (PVP). METHODS: A retrospective study by propensity score matching. From January 2016 to April 2016, 63 patients who were diagnosed with monosegmental osteoporotic vertebral compression fracture received the innovative technique. The epidemiologic data, surgical indexes, and recovery outcomes were collected in the follow-up period. Propensity score matching identified 63 pairs form historical controls by traditional unilateral PVP approach in 2015 using six independent variables: age, sex, preoperative visual analog score (VAS), Oswestry Disability Index (ODI), body mass index, and bone mineral density. RESULTS: The surgical duration and cement distribution were longer and larger in patients by VO method. Besides, postoperative VAS and ODI in the VO group were lower than those in the control group. However, there were no differences in radiation exposure times, improvement of Cobb angle, cement leakage, or adjacent vertebral fracture between two groups. Cement volume in the VO group was less than that in the control group. CONCLUSION: This new innovative technique makes PVP safe and effective. Although it lasts longer, the restoration rate of vertebral height and cement distribution can be improved, which contributes to a better pain relief.

Multilayered Scaffold with a Compact Interfacial Layer Enhances Osteochondral Defect Repair.

Repairing osteochondral defect (OCD) using advanced biomaterials that structurally, biologically, and mechanically fulfill the criteria for stratified tissue regeneration remains a significant challenge for researchers. Here, a multilayered scaffold (MLS) with hierarchical organization and heterogeneous composition is developed to mimic the stratified structure and complex components of natural osteochondral tissues. Specifically, the intermediate compact interfacial layer within the MLS is designed to resemble the osteochondral interface to realize the closely integrated layered structure. Subsequently, macroscopic observations, histological evaluation, and biomechanical and biochemical assessments are performed to evaluate the ability of the MLS of repairing OCD in a goat model. By 48 weeks postimplantation, superior hyalinelike cartilage and sound subchondral bone are observed in the MLS group. Furthermore, the biomimetic MLS significantly enhances the biomechanical and biochemical properties of the neo-osteochondral tissue. Taken together, these results confirm the potential of this optimized MLS as an advanced strategy for OCD repair.

3D-printed scaffolds with calcified layer for osteochondral tissue engineering.

Treating full-layer injury of bone and cartilage is currently a significant challenge in orthopedic trauma repair. Joint damage typically includes chondral defects, and the underlying subchondral defect sites are difficult to repair. Tissue engineering technology could potentially be used to treat such injuries; however, results to date been unsatisfactory. The aim of this study was to design a multilayer composite scaffold containing cartilage, bone, and calcified layers to simulate physiological full-thickness bone-cartilage structure. The cartilage layer was created using an improved temperature-gradient thermally induced crystallization technology. The bone and calcified layers were synthesized using 3D printing technology. We examined the scaffold by using scanning electron microscope (SEM), X-ray diffraction (XRD), fluorescence staining, and micro computed tomography (Micro-CT), and observed clearly oriented structures in the cartilage layer, overlapping structures in the bone scaffold, and a compressed calcified layer. Biomechanical performance testing showed that the scaffolds were significantly stronger than scaffolds without a calcified layer (traditional scaffolds) in maximum tensile strength and maximum shear strength (P < 0.05). After inoculating cells onto the scaffolds, we observed similar cell adherence and proliferation to that observed in traditional scaffolds, likely because of the high porosity of the whole scaffold. Our scaffolds could be used in bone and cartilage full-thickness injury repair methods, as well as applications in the field of tissue engineering.

Is percutaneous kyphoplasty the better choice for minimally invasive treatment of neurologically intact osteoporotic Kümmell's disease? A comparison of two minimally invasive procedures.

PURPOSE: The purpose of this study was to compare and evaluate the safety and efficacy of percutaneous vertebroplasty at a hyperextension position (PVPHP) and percutaneous kyphoplasty at a hyperextension position (PKPHP) for the treatment of osteoporotic Kümmell's disease. METHODS: This study was a retrospective, single-centre study. There were 35 patients with osteoporotic Kümmell's disease who were analyzed. Twenty-two of them underwent PVPHP and the other 13 patients underwent PKPHP from January 2013 to January 2015. The volume of bone cement injection and operation costs were compared. We compared the visual analogue score (VAS) and vertebral Cobb's angle at pre-operation, the second day after operation, and the final follow-up. We compared the Oswestry disability index (ODI) score at the pre-operation and the final follow-up. RESULTS: There were no significant differences in gender, age, course of disease, bone mineral density (BMD), and mean follow-up time between the two groups (P > 0.05). Regarding the costs of the operation, the PKPHP group was significantly higher than the PVPHP group (P < 0.05). Compared with the pre-operation (P < 0.05), the post-operative ODI score, VAS, and Cobb's angle of the two groups were improved significantly. Even though the correction of Cobb's angle in the PKPHP group was slightly better than the PVPHP position group, there were no significant differences between two groups (P > 0.05). At the final follow-up, the Cobb's angle was increased in both groups, but there was no significant difference (P > 0.05). There was no significant difference in the bone cement leakage rate between the two groups (P > 0.05). CONCLUSION: For the treatment of Kümmell's disease, PVPHP and PKPHP are both safe and effective, but PVPHP is more economical and can be considered a preferred method of treatment.

Biomimetic design and fabrication of multilayered osteochondral scaffolds by low-temperature deposition manufacturing and thermal-induced phase-separation techniques.

Integrative osteochondral repair is a useful strategy for cartilage-defect repair. To mimic the microenvironment, it is necessary that scaffolds effectively mimic the extracellular matrix of natural cartilage and subchondral bone. In this study, biomimetic osteochondral scaffolds containing an oriented cartilage layer, a compact layer, and a three-dimensional (3D)-printed core-sheath structured-bone layer were developed. The oriented cartilage layer was designed to mimic the structural and material characteristics of native cartilage tissue and was fabricated with cartilage matrix-chitosan materials, using thermal-induced phase-separation technology. The 3D-printed core-sheath structured-bone layer was fabricated with poly(L-lactide-co-glycolide)/ß-tricalcium phosphate-collagen materials by low-temperature deposition technology, using a specially designed core-sheath nozzle, and was designed to mimic the mechanical characteristics of subchondral bone and improve scaffold hydrophilicity. The compact layer was designed to mimic the calcified-layer structure of natural cartilage to ensure the presence of different suitable microenvironments for the regeneration of bone and cartilage. A dissolving-bonding process was developed to effectively combine the three parts together, after which the bone and cartilage scaffolds exhibited good mechanical properties and hydrophilicity. Additionally, goat autologous bone mesenchymal stem cells (BMSCs) were isolated and then seeded into the bone and cartilage layers, respectively, and following a 1 week culture in vitro, the BMSC-scaffold constructs were implanted into a goat articular-defect model. Our results indicated that the scaffolds exhibited good biocompatibility, and 24 weeks after implantation, the femoral condyle surface was relatively flat and consisted of a large quantity of hyaloid cartilage. Furthermore, histological staining revealed regenerated trabecular bone formed in the subchondral bone-defect area. These results provided a new method to fabricate biomimetic osteochondral scaffolds and demonstrated their effectiveness for future clinical applications in cartilage-defect repair.

In Vivo Evaluation of a Novel Oriented Scaffold-BMSC Construct for Enhancing Full-Thickness Articular Cartilage Repair in a Rabbit Model.

Tissue engineering (TE) has been proven usefulness in cartilage defect repair. For effective cartilage repair, the structural orientation of the cartilage scaffold should mimic that of native articular cartilage, as this orientation is closely linked to cartilage mechanical functions. Using thermal-induced phase separation (TIPS) technology, we have fabricated an oriented cartilage extracellular matrix (ECM)-derived scaffold with a Young's modulus value 3 times higher than that of a random scaffold. In this study, we test the effectiveness of bone mesenchymal stem cell (BMSC)-scaffold constructs (cell-oriented and random) in repairing full-thickness articular cartilage defects in rabbits. While histological and immunohistochemical analyses revealed efficient cartilage regeneration and cartilaginous matrix secretion at 6 and 12 weeks after transplantation in both groups, the biochemical properties (levels of DNA, GAG, and collagen) and biomechanical values in the oriented scaffold group were higher than that in random group at early time points after implantation. While these differences were not evident at 24 weeks, the biochemical and biomechanical properties of the regenerated cartilage in the oriented scaffold-BMSC construct group were similar to that of native cartilage. These results demonstrate that an oriented scaffold, in combination with differentiated BMSCs can successfully repair full-thickness articular cartilage defects in rabbits, and produce cartilage enhanced biomechanical properties.