Dedifferentiation-like reprogramming of degenerative nucleus pulposus cells into notochordal-like cells by defined factors.

The extensive degeneration of functional somatic cells and the depletion of endogenous stem/progenitor populations present significant challenges to tissue regeneration in degenerative diseases. Currently, a cellular reprogramming approach enabling directly generating corresponding progenitor populations from degenerative somatic cells remains elusive. The present study focused on intervertebral disc degeneration (IVDD) and identified a three-factor combination (OCT4, FOXA2, TBXT [OFT]) that could induce the dedifferentiation-like reprogramming of degenerative nucleus pulposus cells (dNPCs) toward induced notochordal-like cells (iNCs). Single-cell transcriptomics dissected the transitions of cell identity during reprogramming. Further, OCT4 was found to directly interact with bromodomain PHD-finger transcription factor to remodel the chromatin during the early phases, which was crucial for initiating this dedifferentiation-like reprogramming. In rat models, intradiscal injection of adeno-associated virus carrying OFT generated iNCs from in situ dNPCs and reversed IVDD. These results collectively present a proof-of-concept for dedifferentiation-like reprogramming of degenerated somatic cells into corresponding progenitors through the development of a factor-based strategy, providing a promising approach for regeneration in degenerative disc diseases.

Comparison of Intraoperative Endplate Injury between Mini-Open Lateral Lumbar Interbody Fusion (LLIF) and Transforaminal Lumbar Interbody Fusion (TLIF) and Analysis of Risk Factors: A Retrospective Study.

OBJECTIVE: The study aimed to compare the incidence of intraoperative endplate injury in patients who underwent Transforaminal interbody fusion (TLIF) and mini-open lumbar interbody fusion (LLIF) surgery. The independent risk factors related to endplate injury in LLIF procedure were analyzed. METHODS: A total of 199 patients who underwent LLIF (n = 106) or TLIF (n = 93) surgery from June 2019 to September 2021 were reviewed. The endplate injury was assessed by postoperative sagittal CT scan. A binary logistic analysis model were used to identify independent risk factors related to LLIF endplate injury based on univariate analysis. RESULTS: There was an obvious difference in the occurrence of intraoperative endplate injury between LLIF (42/106, 39.6%) and TLIF group (26/93, 28%), although it did not reach the significant level. L1 CT value (OR = 0.985, 95% CI = 0.972-0.998), cage position (OR = 3.881, 95% CI = 1.398-10.771) and height variance (OR = 1.263, 95% CI = 1.013-1.575) were independent risk factors for endplate injury in LLIF procedure. According to the cage settlement patterns, there 5 types of A to E. The severity of the facet joint degeneration was positively related to the occurrence of endplate injury. CONCLUSIONS: The incidence of intraoperative endplate injury is higher in LLIF than in TLIF procedures. Low bone quantity, cage posterior position and larger height variance are risk factors to induce endplate injury in LLIF surgery. The facet joint degeneration may be related to severe endplate injuries and even fractures.

Silicate Nanoplatelets Promotes Neuronal Differentiation of Neural Stem Cells and Restoration of Spinal Cord Injury.

Neural stem cell (NSC) transplantation has been suggested as a promising therapeutic strategy to replace lost neurons after spinal cord injury (SCI). However, the low survival rate and neuronal differentiation efficiency of implanted NSCs within the lesion cavity limit the application. Furthermore, it is difficult for transplanted cells to form connections with host cells. Thus, effective and feasible methods to enhance the efficacy of cell transplantation are needed. In this study, the effect of Laponite nanoplatelets, a type of silicate nanoplatelets, on stem cell therapy is explored. Laponite nanoplatelets can induce the neuronal differentiation of NSCs in vitro within five days, and RNA sequencing and protein expression analysis demonstrated that the NF-κB pathway is involved in this process. Moreover, histological results revealed that Laponite nanoplatelets can increase the survival rate of transplanted NSCs and promote NSCs to differentiate into mature neurons. Finally, the formation of connections between transplanted cells and host cells is confirmed by axon tracing. Hence, Laponite nanoplatelets, which drove neuronal differentiation and the maturation of NSCs both in vitro and in vivo, can be considered a convenient and practical biomaterial to promote repair of the injured spinal cord by enhancing the efficacy of NSC transplantation.

Postural deformities in Parkinson's disease: A bibliometric analysis based on web of science.

Objective: Postural deformities are common debilitating conditions during the progression of Parkinson's disease (PD). However, the underlying pathophysiology and optimal treatment strategy are unclear. In this study, we aimed to identify primary research fields, important achievements and emerging trends in postural deformities in PD. Methods: Web of Science Core Collection database was searched to retrieve all literature related to postural deformities in PD over the past 20 years. Data such as annual numbers of publications, countries of origin, publication journals, cooperation between countries, citation index and keywords were retrieved from the selected publications. Bibliometrix Package in R software were used for bibliometric analysis and visualization. Results: In total, 211 publications that met the criteria were collected. Analyses had shown that the annual numbers of publications increased gradually with fluctuations. Japan was the most prolific country (n = 59). Italy participated in international cooperation the most frequently. Parkinsonism & related disorders (n = 25) took a prominent lead among all journals, and the most productive institution in this area was University of Verona (n = 27). The most local cited author was Tinazzi Michele. According to the thematic map, "scoliosis", "fusion", and "balance" have rapidly become research hot spots in related fields. Conclusions: Articles pertaining to postural deformities in PD are still being published, in which the etiology is a combination of peripheral plus central involvement. Treatment approaches include rehabilitative exercises, oral medication, botulinum toxin injection, deep brain stimulation and spine surgery, which is getting current attention and would be a hot topic of future research.

Nucleus pulposus cell-derived efficient microcarrier for intervertebral disc tissue engineering.

Adipose-derived stem cells (ADSCs) show great potential for the treatment of intervertebral disc (IVD) degeneration. An ideal carrier is necessary to transplant ADSCs into degenerated IVDs without influencing cell function. Nucleus pulposus cells (NPCs) can synthesize and deposit chondroitin sulfate and type II collagen which are NP-specific extracellular matrix (ECM) and can also regulate the NP-specific differentiation of stem cells. Bioscaffolds fabricated based on the ECM synthesis functions of NPCs have possible roles in cell transplantation and differentiation induction, but it has not been studied. In this study, we first aggregated NPCs into pellets, and then, NPC-derived efficient microcarriers (NPCMs) were fabricated by pellet cultivation under specific conditions and optimized decellularization. Thirdly, we evaluated the microstructure, biochemical composition, biostability and cytotoxicity of the NPCMs. Finally, we investigated the NP-specific differentiation of ADSCs induced by the NPCMsin vitroand NP regeneration induced by the ADSC-loaded NPCMs in a rabbit model. The results indicated that the injectable NPCMs retained maximal ECM and minimal cell nucleic acid after optimized decellularization and had good biostability and no cytotoxicity. The NPCMs also promoted the NP-specific differentiation of ADSCsin vitro. In addition, the results of MRI, x-ray, and the structure and ECM content of NP showed that the ADSCs-loaded NPCMs can partly restored the degenerated NPin vivo. Our injectable NPCMs regenerated the degenerated NP and provide a simplified and efficient strategy for treating IVD degeneration.

An esterase-responsive ibuprofen nano-micelle pre-modified embryo derived nucleus pulposus progenitor cells promote the regeneration of intervertebral disc degeneration.

Stem cell-based transplantation is a promising therapeutic approach for intervertebral disc degeneration (IDD). Current limitations of stem cells include with their insufficient cell source, poor proliferation capacity, low nucleus pulposus (NP)-specific differentiation potential, and inability to avoid pyroptosis caused by the acidic IDD microenvironment after transplantation. To address these challenges, embryo-derived long-term expandable nucleus pulposus progenitor cells (NPPCs) and esterase-responsive ibuprofen nano-micelles (PEG-PIB) were prepared for synergistic transplantation. In this study, we propose a biomaterial pre-modification cell strategy; the PEG-PIB were endocytosed to pre-modify the NPPCs with adaptability in harsh IDD microenvironment through inhibiting pyroptosis. The results indicated that the PEG-PIB pre-modified NPPCs exhibited inhibition of pyroptosis in vitro; their further synergistic transplantation yielded effective functional recovery, histological regeneration, and inhibition of pyroptosis during IDD regeneration. Herein, we offer a novel biomaterial pre-modification cell strategy for synergistic transplantation with promising therapeutic effects in IDD regeneration.

Swelling-Mediated Mechanical Stimulation Regulates Differentiation of Adipose-Derived Mesenchymal Stem Cells for Intervertebral Disc Repair Using Injectable UCST Microgels.

Mechanical stimulation is an effective approach for controlling stem cell differentiation in tissue engineering. However, its realization in in vivo tissue repair remains challenging since this type of stimulation can hardly be applied to injectable seeding systems. Here, it is presented that swelling of injectable microgels can be transformed to in situ mechanical stimulation via stretching the cells adhered on their surface. Poly(acrylamide-co-acrylic acid) microgels with the upper critical solution temperature property are fabricated using inverse emulsion polymerization and further coated with polydopamine to increase cell adhesion. Adipose-derived mesenchymal stem cells (ADSCs) adhered on the microgels can be omnidirectionally stretched along with the responsive swelling of the microgels, which upregulate TRPV4 and Piezo1 channel proteins and enhance nucleus pulposus (NP)-like differentiation of ADSCs. In vivo experiments reveal that the disc height and extracellular matrix content of NP are promoted after the implantation with the microgels. The findings indicate that swelling-induced mechanical stimulation has great potential for regulating stem cell differentiation during intervertebral disc repair.

Effect of C1 Single-door Laminoplasty on Symptomatic Atlas Canal Stenosis.

OBJECTIVE: To verify the effect of single-door laminoplasty combined with atlantoaxial fusion in the treatment of symptomatic atlas canal stenosis. METHODS: This is a single-center retrospective analysis. From February 2014 to January 2019, 16 patients (five were females) with an average age of 63.4 years (56-71 years) were enrolled in this study. Patients with compressive cervical myelopathy with CT scan showed an inner sagittal diameter (ISD) of C1 less than 29 mm or C1 canal space available for cord (SAC) of <12 mm were included, while isolated C1 stenosis without myelopathy or isolated C1 stenosis without atlantoaxial subluxation were excluded in this study. All patients underwent continuous heavy-weight skull traction, atlas single-door laminoplasty and atlantoaxial fusion. The differences in the pre- and post-operative inner sagittal diameter, space available for cord, atlas-dens interval (ADI) and compression of the spinal cord were analyzed by using CT and MRI. Functional evaluation was performed by using the Japanese Orthopaedic Association scoring system and the Neck Disability Index scoring system. RESULTS: Single-door laminoplasty provided a full decompression for the spinal cord while retaining the whole posterior arch. No complications were encountered except a superficial wound infection in one patient. At final follow-up, The ADI was significantly reduced from 5.2 ± 1.8 mm to 1.7 ± 0.6 mm after surgery on average (P < 0.05). Average inner sagittal diameter of C1 was increased from 26.3 ± 2.6 mm to 34.9 ± 2.9 mm and the space available for cord was increased from 6 ± 1.7 mm to 17.8 ± 3.6 mm (P < 0.05). Meanwhile, the Japanese Orthopaedic Association (JOA) score of the 16 cases was improved from 11.4 ± 1.8 to 14.1 ± 1.4 on average (P < 0.05). The postoperative neck pain VAS score decreased significantly, from 2.6 ± 1.0 preoperatively to 1.3 ± 0.9 postoperatively (P < 0.05). The influence of neck pain on patient's life was improved from 17.8 ± 3.9 to 13.9 ± 3.3 after surgery (P < 0.05). At the last follow-up, the healing of the hinge fracture and the fusion between atlas and axis were observed in all patients. CONCLUSIONS: Single-door laminoplasty combined with atlantoaxial fusion not only provides enough space for decompression but also offers intact arch for bone grafting, suggesting that it might provide a more feasible method for the correction of symptomatic atlas canal stenosis.

Clinical Results of Utilizing the Satellite Rod Technique in Treating Ankylosing Spondylitis Kyphosis.

OBJECTIVE: According to the literature, there are no clinical reports documenting the use of the satellite rod technique in the treatment of ankylosing spondylitis kyphosis. The purpose of this retrospective study was to compare the clinical outcome of patients with ankylosing spondylitis kyphosis who adopted satellite rods versus those who did not. METHODS: Patients with ankylosing spondylitis kyphosis who underwent one or two-level pedicle subtraction osteotomy (PSO) were reviewed, and total of 119 patients (112 males and seven females, average age 39.89 ± 6.61 years) were eligible and included in this present study. Anterior-posterior and lateral full-length spine X-ray films were performed preoperatively and at the two-year follow-up visit. Global kyphosis (GK), lumbar lordosis (LL), thoracolumbar kyphosis (TLK), thoracic kyphosis (TK), and osteotomy angle (OA) were measured. The complications of every group of patients were collected. Pre- and postoperative health-related quality of life instruments, including the Bath Ankylosing Spondylitis Functional Index (Basfi) and Scoliosis Research Society outcomes instrument-22 (SRS-22), were recorded. The patients were divided into three groups based on features of their osteotomy including PSO levels and whether the satellite rod technique was applied. Patients who underwent one-level PSO without the satellite rod technique were categorized in the one-level group. Patients who underwent one-level PSO with the satellite rod technique were classified in the satellite rod group. Patients who underwent two-level PSO without the satellite rod technique were included in the two-level group. The paired sample t test was used to compare pre- and postoperative parameters. One-way ANOVA was performed for multiple group comparisons. RESULTS: The average follow-up time is 29.31 ± 3.66 months. The patients' GK were significantly improved from 46.84 ± 20.37 degree to 3.31 ± 15.09 degree. OS achieved through each osteotomy segment of one-level group (39.78 ± 12.29 degree) and satellite rods group (42.23 ± 9.82 degree), was larger than that of two-level group (34.73 ± 7.54 and 28.85 ± 7.26 degree). There was no significant difference between the one-level group and the satellite rod group in achieving the OS. Thirteen patients experienced different complications (10.92%). Three patients experienced rod fracture in the one-level group. There was no rod fracture or screw failure in the satellite rod group or the two-level group. CONCLUSION: The satellite rod technique is also recommended for patients who undergo PSO osteotomy to correct ankylosing spondylitis kyphosis deformities.

Effect of miRNA-146a-mediated TLR4 Signal Pathway on the Pain of Lumbar Disc Herniation.

The current experiment was carried out to explore the effect of the miR-146a-mediated TLR4 signaling pathway on the lumbar disc herniation pains. For this aim, a total of 32 rats were divided randomly into 4 groups - the blank group (Group C), Model group (M), miR-146a overexpression group (agomiR-146a group) and negative control group (NC group), with 8 rats in each group. Rats in Group M were prepared for the construction of lumbar disc herniation models, while those in the agomiR-146a group or NC group, in addition to the model construction, would receive the intrathecal injection of agomiR-146a or agomiRNA-146a NC. Thereafter, a series of tests were performed for rats, including the mechanical pain test and heat pain test to measure the pain threshold, RT-PCR to detect the expression of miR-146a, and the transcription of TLR4, IRAK1, TRAF6, IL-6 and TNF-α, Western blot to determine the expression of IRAK1 and TRAF6 and ELISA to determine the expression of IL-6 and TNF-α. Results showed that as compared to the blank group, rats in Group M were more sensitive to the pains, presenting with declines in the thresholds in the pain, and upregulation in the TRL4 signaling pathway (TLR4, IRAK1 and TRAF6) and pro-inflammatory factors, including IL-6 and TNF-α. In comparison with Group M, intrathecal injection of agomiR-146a relieved the pains, with significant upregulation of miR-146a and downregulation of TLR4, IRAK1, TRAF6, IL-6 and TNF-α. Then upregulation of miR-146a could reduce the activity of the TLR4 signaling pathway and the release of pro-inflammatory factors, which may be a potential strategy for the treatment of lumbar disc herniation.

A conductive supramolecular hydrogel creates ideal endogenous niches to promote spinal cord injury repair.

The current effective method for treatment of spinal cord injury (SCI) is to reconstruct the biological microenvironment by filling the injured cavity area and increasing neuronal differentiation of neural stem cells (NSCs) to repair SCI. However, the method is characterized by several challenges including irregular wounds, and mechanical and electrical mismatch of the material-tissue interface. In the current study, a unique and facile agarose/gelatin/polypyrrole (Aga/Gel/PPy, AGP3) hydrogel with similar conductivity and modulus as the spinal cord was developed by altering the concentration of Aga and PPy. The gelation occurred through non-covalent interactions, and the physically crosslinked features made the AGP3 hydrogels injectable. In vitro cultures showed that AGP3 hydrogel exhibited excellent biocompatibility, and promoted differentiation of NSCs toward neurons whereas it inhibited over-proliferation of astrocytes. The in vivo implanted AGP3 hydrogel completely covered the tissue defects and reduced injured cavity areas. In vivo studies further showed that the AGP3 hydrogel provided a biocompatible microenvironment for promoting endogenous neurogenesis rather than glial fibrosis formation, resulting in significant functional recovery. RNA sequencing analysis further indicated that AGP3 hydrogel significantly modulated expression of neurogenesis-related genes through intracellular Ca2+ signaling cascades. Overall, this supramolecular strategy produces AGP3 hydrogel that can be used as favorable biomaterials for SCI repair by filling the cavity and imitating the physiological properties of the spinal cord.

Partial reprogramming strategy for intervertebral disc rejuvenation by activating energy switch.

Rejuvenation of nucleus pulposus cells (NPCs) in degenerative discs can reverse intervertebral disc degeneration (IDD). Partial reprogramming is used to rejuvenate aging cells and ameliorate progression of aging tissue to avoiding formation of tumors by classical reprogramming. Understanding the effects and potential mechanisms of partial reprogramming in degenerative discs provides insights for development of new therapies for IDD treatment. The findings of the present study show that partial reprogramming through short-term cyclic expression of Oct-3/4, Sox2, Klf4, and c-Myc (OSKM) inhibits progression of IDD, and significantly reduces senescence related phenotypes in aging NPCs. Mechanistically, short-term induction of OSKM in aging NPCs activates energy metabolism as a "energy switch" by upregulating expression of Hexokinase 2 (HK2) ultimately promoting redistribution of cytoskeleton and restoring the aging state in aging NPCs. These findings indicate that partial reprogramming through short-term induction of OSKM has high therapeutic potential in the treatment of IDD.

Enhancement of nucleus pulposus repair by glycoengineered adipose-derived mesenchymal cells.

Adipose-derived mesenchymal stem cells (ADSCs) are promising candidates for repairing degenerated intervertebral discs through multiple means, including: i. Secretion of bioactive factors to regulate inflammation and, ii. The potential to differentiate into nucleus pulposus (NP)-like cells, which can integrate into host tissues. However, the differentiation ability of ADSCs to NP-like cells is limited, which emphasizes on the need for alternative approaches to regulate cell differentiations. Given that cell functions are influenced by interactions between the extracellular matrix (ECM) and cells, we hypothesize that cell surface modification promotes ADSCs adhesion and differentiation towards NP-like cells. In this study, cell surfaces of ADSCs were functionalized with unnatural sialic acid via metabolic glycoengineering. Subsequently, adhesion abilities of modified cells to three main ECM (laminin, collagen and fibronectin) were compared. The adhesion assay revealed that glycoengineered ADSCs had the highest affinity for collagen, compared to laminin and fibronectin. Moreover, cultures with collagen coated plates enhanced the differentiation of glycoengineered ADSCs to NP-like cells. Metabolic glycoengineering prolonged ADSCs viability. The glycoengineered ADSCs increased the height and elasticity of intervertebral discs, as well as the water content and ECM volumes of nucleus pulposus. In conclusion, metabolic glycoengineering of cell surfaces has a significant role in modulating cell biological functions and promoting NP tissue repair.

A Crucial But Neglected Anatomical Factor Underneath Psoas Muscle and Its Clinical Value in Lateral Lumbar Interbody Fusion-The Cleft of Psoas Major (CPM).

OBJECTIVE: To describe the anatomical feature positioned beneath the psoas muscle at the lateral aspect of the lower lumbar, and to create a new location system to identify the risk factors of lateral lumbar interbody fusion. METHODS: Six cadavers were dissected and analyzed. The anatomy and neurovascular distribution beneath the psoas major from L3 to S1 was observed and recorded, with particular focus on the L4/5 disc and below. The psoas major surface was divided homogeneously into four parts, from the anterior border of psoas major to the transverse process. The cranial-to-caudal division was from the lower edge of the psoas muscle attachment on the L4 vertebrae to the upper part of the S1 vertebrae, and was divided into five segments. Then a grid system was used to create 20 grids on the psoas major surface, from the anterior border of the muscle to the transverse process and from L4 to superior S1 , which was used to determine the anatomical structures' distribution and relationship beneath the psoas major. RESULTS: A cleft was identified beneath the psoas major, from the level of L4/5 downwards. It was filled with loose connective tissue and neurovascular structures. We termed it the cleft of psoas major (CPM). The sympathetic trunk, ascending lumbar vein, iliolumbar vessels, obturator nerve, femoral nerve and occasionally the great vessels are contained within the CPM, although there is significant interpersonal variation. The grid system on the psoas major surface helped to identify the anatomical structures in CPM. There was a considerably lower frequency of occurrence of neurovascular structures in the grids of I/II at the L4/5 level where can be considered the "safe zones" for the lateral lumbar interbody fusion. In contrast, the distribution of neurovascular structures at the L5 S1 level is dense, where the operation risk is high. CONCLUSION: The CPM exists lateral to the vertebral surface from L4 and below. Although the occurrence and distribution of neurovascular structures within the CPM is complex and varies greatly, it can provide a potential cavity for visualization during lateral lumbar interbody fusion. Using psoas major as a reference, this novel grid system can be used to identify the risk factors in CPM and thus identify a safe entry point for surgery.

Anterior Selective Lumbar Fusion Saving More Distal Fusion Segments Compared with Posterior Approach in the Treatment of Adolescent Idiopathic Scoliosis with Lenke Type 5: A Cohort Study with More Than 8-Year Follow-up.

OBJECTIVE: To investigate whether anterior selective fusion (ASF) could save more distal fusion segments compared with posterior approach in the treatment of Lenke type 5 adolescent idiopathic scoliosis with long term follow-up. METHODS: A retrospective cohort study. From 2008 to 2011, 22 AIS girls with Lenke type 5 who underwent ASF or posterior selective fusion (PSF) with more than 8-year follow-up, were extracted from the database. 13 girls in the ASF group had an average age of 14.3 ± 1.3 years and Risser sign of 3.3 ± 1.1; 9 PSF girls had an average age of 16.2 ± 3.6 years and Risser sign of 3.8 ± 1.5. The radiographic outcome was compared between groups preoperatively, 6-month postoperatively, 8-year postoperatively and at last follow-up (>8 years). RESULTS: The average follow-up duration was 8.7 ± 0.4 (ASF) and 8.8 ± 0.5 (PSF) years, respectively. There was no significant difference at baseline in age, Risser sign and preoperative curve pattern in the coronal and sagittal plane between the groups (P > 0.05). The ASF group had significantly shorter fusion segments (5.1 ± 0.6 vs. 7.0 ± 1.3) and decreased upper instrumented vertebra (UIV) (T11 ± 0.8 vs. T10 ± 0.8) than the PSF (P < 0.05); while no significant difference was found in the lower instrumented vertebra (LIV) and distal reserved segments (P > 0.05), which suggested that ASF could shorten the fusion segments by lowering UIV. The distal compensatory curve in the ASF group (9.0° ± 3.9°) was significantly larger than in the PSF group (3.3° ± 2.4°, P = 0.003), despite of no significant difference in the incidence of coronal imbalance (P > 0.05), indicating that both two approaches could obtain satisfactory correction in the coronal plane. In the sagittal plane, PSF patients had significantly larger lumbar lordosis (LL, 59.1° ± 10.5°), thoracic kyphosis (TK, 37.2° ± 13.3°) and proximal junctional angle (PJA, 13.3° ± 6.1°) at the last follow-up than the ASF (LL: 43.4° ± 9.4°; TK: 20.7° ± 8.4°; PJA: 4.7° ± 3.4°; P < 0.05), but without significant difference in proximal junctional kyphosis (PJK) and sagittal vertical axis (SVA) (P > 0.05). After controlling for age, Risser sign, and radiographic parameters related to the primary curve pattern, shorter fusion segments and more distal reserved segments still remained significant in the ASF group with greater Risser sign (P < 0.05). No major intra- or post-operative complications occurred. CONCLUSIONS: Both ASF and PSF could obtain satisfactory coronal and sagittal correction for Lenke 5 AIS; compared with PSF, ASF could shorten the fusion segments by lowering UIV, and save more distal fusion segments only in patients with greater skeletal maturity.

Incidence and risk factors of lateral cage migration occurred after the first-stage lateral lumbar interbody fusion surgery.

BACKGROUND: Lateral lumbar interbody fusion (LLIF) is a novel, minimally invasive technique for the surgical treatment of lumbar diseases. The aim of this study was to identify the incidence and risk factors of lateral cage migration (LCM) occurred after the first-stage LLIF. HYPOTHESIS: The hypothesis was that LCM occurred after the first-stage LLIF was associated with some demographic characteristics, surgical variables and radiographic parameters. PATIENTS AND METHODS: Between June 2016 and August 2020, 335 patients (901 levels) underwent staged LLIF were retrospectively reviewed. Patients were classified into LCM and non-LCM group based on the experience of LCM before the second-stage posterior instrumentation. 100 patients in non-LCM were randomly sampled as a control group. Incidence of LCM was determined; demographic characteristics, surgical variables and radiographic parameters associated with LCM were compared between the LCM and control group. Univariate analyses and multivariable logistic regression analysis were used to identify the risk factors. RESULTS: LCM occurred after the first-stage LLIF was found in 19 (5.7%) patients. Bony endplate injury (OR, 106.255; 95% CI, 1.265-8924.765; p=0.039) and greater preoperative range of motion (ROM) (OR, 2.083, 95% CI, 1.068-4.066, p=0.031) were high risk factors for LCM. LCM occurred mainly 3 days later after the first-stage LLIF, while 4 cases experienced severe neural symptoms, intolerable low back pain and finally underwent reoperation. DISCUSSION: LCM occurred after the first-stage LLIF was significantly associated with bony endplate injury and greater preoperative ROM. Second-stage posterior fixation should be performed as soon as possible or a supplement lateral fixation/self-locking cage should be used in high-risk patients. LEVEL OF EVIDENCE: IV.

Injectable kartogenin and apocynin loaded micelle enhances the alleviation of intervertebral disc degeneration by adipose-derived stem cell.

Cell transplantation has been proved the promising therapeutic effects on intervertebral disc degeneration (IVDD). However, the increased levels of reactive oxygen species (ROS) in the degenerated region will impede the efficiency of human adipose-derived stem cells (human ADSCs) transplantation therapy. It inhibits human ADSCs proliferation, and increases human ADSCs apoptosis. Herein, we firstly devised a novel amphiphilic copolymer PEG-PAPO, which could self-assemble into a nanosized micelle and load lipophilic kartogenin (KGN), as a single complex (PAKM). It was an injectable esterase-responsive micelle, and showed controlled release ability of KGN and apocynin (APO). Oxidative stimulation promoted the esterase activity in human ADSCs, which accelerate degradation of esterase-responsive micelle. Compared its monomer, the PAKM micelle possessed better bioactivities, which were attributed to their synergistic effect. It enhanced the viability, autophagic activation (P62, LC3 II), ECM-related transcription factor (SOX9), and ECM (Collagen II, Aggrecan) maintenance in human ADSCs. Furthermore, it is demonstrated that the injection of PAKM with human ADSCs yielded higher disc height and water content in rats. Therefore, PAKM micelles perform promoting cell survival and differentiation effects, and may be a potential therapeutic agent for IVDD.

Is stand-alone lateral lumbar interbody fusion superior to instrumented lateral lumbar interbody fusion for the treatment of single-level, low-grade, lumbar spondylolisthesis?

BACKGROUND: The aim of this study was to compare surgical trauma and radiographic and clinical outcomes of stand-alone and instrumented lateral lumbar interbody fusion (LLIF) in the treatment of single-level low-grade lumbar spondylolisthesis. METHODS: Ninety-five patients with single-level low-grade lumbar spondylolisthesis, who underwent stand-alone LLIF (stand-alone group, [n = 54]) or LLIF plus percutaneous posterior fixation (instrumented group, [n = 41]) were enrolled in this study. Operative time, intraoperative blood loss, serum C-reactive protein (CRP) and creatine kinase (CK) levels, the length of postoperative bed rest time, and hospital stay were compared between the 2 groups. Disc height, the percent of slip, segment lordosis, lumbar lordosis, the visual analog scale score, the Oswestry Disability Index and complications were also compared. RESULTS: Operative and bed rest time were shorter, intraoperative blood loss was less, and postoperative CRP and CK levels were lower in the stand-alone group. During follow-up, 6 patients in stand-alone group underwent posterior fixation due to cage subsidence. Although satisfactory radiographic results were achieved in both groups, the maintenance of increased disc heights and segment lordosis was inferior in the stand-alone group at the final follow-up. Greater improvement in postoperative VAS scores and ODI were observed in the stand-alone group, although the rates of cage subsidence and revision were higher. CONCLUSION: Stand-alone LLIF was superior to instrumented LLIF in terms of tissue trauma for the treatment of single-level low-grade lumbar spondylolisthesis. However, stand-alone LLIF was inferior in the maintenance of disc height and segment lordosis, and the occurrence of cage subsidence and revision.

A bioactive injectable self-healing anti-inflammatory hydrogel with ultralong extracellular vesicles release synergistically enhances motor functional recovery of spinal cord injury.

The repair and motor functional recovery after spinal cord injury (SCI) remains a worldwide challenge. The inflammatory microenvironment is one of main obstacles on inhibiting the recovery of SCI. Using mesenchymal stem cells (MSCs) derived extracellular vesicles to replace MSCs transplantation and mimic cell paracrine secretions provides a potential strategy for microenvironment regulation. However, the effective preservation and controlled release of extracellular vesicles in the injured spinal cord tissue are still not satisfied. Herein, we fabricated an injectable adhesive anti-inflammatory F127-polycitrate-polyethyleneimine hydrogel (FE) with sustainable and long term extracellular vesicle release (FE@EVs) for improving motor functional recovery after SCI. The orthotopic injection of FE@EVs hydrogel could encapsulate extracellular vesicles on the injured spinal cord, thereby synergistically induce efficient integrated regulation through suppressing fibrotic scar formation, reducing inflammatory reaction, promoting remyelination and axonal regeneration. This study showed that combining extracellular vesicles into bioactive multifunctional hydrogel should have great potential in achieving satisfactory locomotor recovery of central nervous system diseases.

The effect of sarcopenia in the clinical outcomes following stand-alone lateral lumbar interbody fusion.

BACKGROUND: Sarcopenia has been found to affect the postoperative outcomes of lumbar surgery. The effect of sarcopenia on the clinical outcomes in patients who underwent stand-alone lateral lumbar interbody fusion (LLIF) has not yet been examined. OBJECTIVE: To investigate whether sarcopenia affects the Oswestry Disability Index (ODI) and visual analog scale (VAS) score for back pain following single-level stand-alone LLIF. METHODS: Patients who underwent a single level stand-alone LLIF for lumbar diseases were retrospectively investigated. Sarcopenia was defined according to the diagnostic algorithm recommended by the Asian Working Group for Sarcopenia. Patients were divided into the sarcopenia (SP) and non-sarcopenia (NSP) group. Univariate analysis was used to compare with regards to demographics and clinical outcomes. Multivariate logistic regression was performed to elucidate factors predicting poor clinically improvement. RESULTS: Sixty-nine patients were enrolled, with 16 and 53 patients in the SP and NSP group respectively. In the SP group, patients were much older (P= 0.002), their body mass index was significantly lower (P< 0.001), the percent of women was higher (P= 0.042), and the skeletal muscle mass index (SMI) (P< 0.001) and gait speed were much lower (P= 0.005). The postoperative ODI scores were much higher and the improvement rate was much lower (both P< 0.001) in the SP group, whereas VAS scores for back pain showed no difference between the two groups. SMI and gait speed had a moderate and weak correlation with the final ODI score, respectively. Low SMI and low gait speed were independently associated with poor clinical outcomes at the final follow-up. CONCLUSIONS: Sarcopenia impacts the final clinical outcomes of stand-alone LLIF for lumbar diseases. Low SMI and low gait speed were negative impact factors for the clinical improvement after stand-alone LLIF.