ABSTRACT Background Achieving rapid bone fusion is critical for preventing complications in Extreme Lateral Interbody Fusion (XLIF), yet harvesting sufficient autologous bone presents surgical limitations. Platelet‐rich fibrin (PRF), an autologous biomaterial rich in osteogenic growth factors, offers potential as a bone graft enhancer. This study evaluated the efficacy of PRF combined with allogeneic bone in promoting interbody fusion using an XLIF‐simulated rabbit model. Methods In vitro, bone marrow mesenchymal stem cells were cultured with PRF, allogeneic bone, or PRF/allogeneic bone composites. Assessments included biocompatibility (CCK‐8, Calcein‐AM/PI), cell adhesion (phalloidin/DAPI), and osteogenic differentiation (alkaline phosphatase activity/staining, Alizarin Red S). PRF, allogeneic bone, and their composite (PRF/allogeneic bone) were evaluated in a rabbit XLIF model. Autologous iliac crest bone served as a positive control, while empty cages provided negative controls. Endpoints included radiographic (micro‐CT), mechanical (biomechanical testing), histological (H&E, methylene blue–acid fuchsin, TRAP), and biochemical (ELISA) evaluation at postoperative 2, 4, 8, and 12 weeks. Results In vitro experiments demonstrated that PRF/allogeneic bone composites exhibited noncytotoxic properties and osteogenic‐promoting effects when combined with titanium alloy cages. In vivo, fusion progressed temporally across all groups, with the PRF/allogeneic bone composite yielding 12‐week fusion rates by manual palpation and micro‐CT equivalent to autograft. Biomechanical strength and bone mineral density of PRF/allogeneic bone matched autograft, exceeding allogeneic bone. Histology demonstrated accelerated fusion kinetics: early angiogenesis (2 weeks), fibrocartilage formation (4 weeks), and complete trabecular bridging by 12 weeks. ELISA confirmed earlier BMP‐2/VEGF peaks (2–4 weeks) versus allogeneic bone. Conclusions These results indicated that the combination of PRF and allogeneic bone successfully induced intervertebral bone formation in the rabbit XLIF model. PRF can serve as a physiological natural fusion material, inducing osteogenesis and achieving spinal fusion. Its osteopromotive effects, cost‐effectiveness, and autologous origin support its potential as a superior graft alternative for XLIF procedures.

Extracellular vesicles (EVs), particularly small extracellular vesicles (sEVs) defined as vesicles smaller than 200 nm, serve as essential mediators of intercellular communication and released by nearly all cell types into various biological fluids. The infrapatellar fat pad (IPFP) is closely associated with the development and progression of knee osteoarthritis (OA). However, standardized methods for isolating sEVs directly from IPFP explants remain limited. We present a reproducible protocol for the isolation and characterization of sEVs derived from IPFP tissues obtained from OA patients. Conditioned medium collected from IPFP tissue cultures is sequentially cleared of cells and debris by low-speed centrifugation, followed by ultracentrifugation to enrich vesicles within the sEV size range. The resulting vesicles are characterized according to minimal information for studies of extracellular vesicles (MISEV2023) recommendations using a set of representative protein markers across distinct functional categories: CD63 as a membrane-associated tetraspanin, ALIX and TSG101 as cytosolic proteins involved in biogenesis mediated by the Endosomal Sorting Complex Required for Transport (ESCRT) machinery, and Calnexin as an endoplasmic reticulum-resident protein to monitor potential non-vesicular contamination. This workflow yields well-defined sEV preparations suitable for downstream applications such as functional assays or proteomic profiling in osteoarthritis research.

Unicompartmental knee arthroplasty (UKA) is widely recognized as an effective treatment for advanced knee osteoarthritis. However, its dependency on surgical experience and two-dimensional (2D) radiographs introduces significant challenges for less-experienced surgeons and for patients with femoral or tibial bone deformities. To enhance surgical precision and reduce prosthesis malposition-related complications, our team integrated three-dimensional (3D) printing technology for patient-specific instrumentation (PSI) with artificial intelligence (AI)-based preoperative simulation planning, thereby addressing the limitations of traditional approaches. This study presents a comprehensive digital workflow for fixed-bearing UKA that aims to achieve precise prosthetic alignment, improve surgical efficiency and safety, reduce operative time, and enable personalized prosthesis positioning with consistent and reproducible outcomes. The protocol consists of five critical steps: 1. Strict patient selection based on fixed-bearing UKA indications; 2. Comprehensive imaging acquisition, including CT scans of the affected knee, anteroposterior and lateral radiographs, and full-length weight-bearing X-rays in DICOM format; 3. AI-assisted preoperative planning with detailed surgical simulation reports; 4. Fabrication of customized 3D-printed cutting guides; 5. Precise osteotomy execution with intraoperative verification. By implementing this standardized digital approach, we demonstrate how integrating AI and 3D printing can optimize UKA outcomes through enhanced reproducibility, accuracy, and patient-specific customization.

Intervertebral disc (IVD) degeneration is an age-related problem triggering chronic spinal issues, such as low back pain and IVD herniation. Standard surgical treatment for such spinal issues is the removal of the degenerated or herniated IVD and fusion of adjacent vertebrae to stabilise the joint and locally decompress the spinal cord and/or nerve roots to relieve pain. However, a key challenge of current surgical strategies is the increasing risk of adjacent segment degeneration due to the disruption of native biomechanics of the functional spinal unit, dominated by the loss of the IVD. In the past two decades, research has focused on developing a number of bioengineering approaches to repair and regenerate the IVD; in particular, tissue engineering of the IVD, using bioscaffolds and stem cells represents a promising area. This review highlights the current tissue engineering approaches utilising biomaterials, animal models and cell sources for IVD regeneration and discusses future opportunities.

This study addresses the clinical challenge of nonunion in spinal interbody fusion by developing a novel composite implant: a porous tantalum (PTa) cage loaded with concentrated growth factors (CGF). The CGF-PTa cage synergistically combines the mechanical strength and osteoconductivity of chemically vapor-deposited PTa with the sustained release of angiogenic (VEGF) and osteogenic (TGF-β and IGF-1) factors from CGF. Using a rat extreme lateral interbody fusion (XLIF) model, the research systematically evaluates the efficacy of this composite in promoting bone regeneration and spinal fusion. Results from radiography, micro-CT, biomechanical testing, histological staining, and immunohistochemistry consistently show that CGF-PTa significantly enhances bone ingrowth, fusion rate, and mechanical stability compared to PTa alone. The findings also reveal that CGF facilitates angiogenesis and osteogenesis by modulating the local healing microenvironment and promoting vascular–osteogenic coupling. Importantly, the CGF-PTa system demonstrated excellent biocompatibility and biodegradability in vivo, with no observed systemic toxicity. This work highlights the potential of combining bioactive factors with porous metallic scaffolds to overcome the limitations of inert implants in avascular environments, offering a promising strategy for functional optimization of interbody fusion devices and their future clinical application.

Background:Estrogen can inhibit the apoptosis of nucleus pulposus cells (NPCs) through the PI3K/AKT/mTOR signaling pathway. However, the downstream of mTOR signaling pathway remains elusive. This study investigates the effect of 17β-estradiol (E2) on intervertebral disc degeneration (IVDD) through the p70 S6K1 signaling pathway, downstream of mTOR. Methods:The IVDD model of rats was established by needle puncture and bilateral ovariectomy. Fifteen Sprague-Dawley rats were randomly assigned to the following three groups: (A) Sham surgery group (Sham); (B) Bilateral ovariectomy, 21G needle puncture and carrier injection (OVX + veh); (C) Bilateral ovariectomy, 21G needle puncture, E2 supplementation (OVX + E2). The degree of IVDD was evaluated by X-ray, magnetic resonance imaging (MRI), hematoxylin and eosin (H&E), and Safranin O-Fast Green staining. The expression levels of target protein p70S6K1 and its phosphorylated products were detected by immunohistochemistry (IHC). Finally, Western blot analysis and immunofluorescence staining were used to investigate the effect of E2 on the p70 S6K1 signaling pathway in vitro. Results:Histological staining and radiological results showed that E2 supplementation altered signaling, suggesting that it may have a protective effect against IVDD. IHC showed that compared with the Sham and OVX + E2 groups, the level of p70 S6K1 in the OVX + veh group was significantly increased while the expression of phosphorylated products (p-S6) was significantly decreased, suggesting that E2 could inhibit IVDD by activating p70 S6K1 signaling pathway, the downstream of mTOR. Furthermore, cellular immunofluorescence and Western blot showed that E2 can maintain extracellular matrix (ECM) balance and inhibits apoptosis of nucleus pulposus cells (NPCs) by activating the p70 S6K1 signaling pathway. Conclusion:In summary, 17β-estradiol mitigates IVDD progression by maintaining ECM homeostasis and inhibiting NPCs apoptosis through activation of the p70 S6K1 signaling pathway downstream of mTOR.

Background:Preclinical animal models are indispensable for the development of new therapeutic strategies and the study of the pathological mechanisms of intervertebral disc (IVD) degeneration (IVDD). This study aims to develop a reliable and reproducible rat model of IVDD by injecting advanced glycation end products (AGEs) into the IVD of ovariectomized rats. Methods:Twenty-eight female Sprague-Dawley rats were allocated into the 31G needle group, vehicle group, 0.5 μg AGEs group, 1 μg AGEs group, 2 μg AGEs group, 4 μg AGEs group, and non-ovariectomy group (n = 4). The coccygeal discs of the 31G needle group were punctured only, while the coccygeal discs of the vehicle group were injected with 1 μL PBS. The coccygeal discs of the AGEs groups underwent injection of AGEs at 0.5, 1, 2, and 4 μg, respectively. The coccygeal discs of the non-ovariectomy group were injected with 2 μg AGEs. Rats in all groups, except for the non-ovariectomy group, underwent bilateral ovariectomy. Two weeks later, the rat caudal models were evaluated using radiological examination, histological staining, and immunohistochemistry (IHC). Results:No signs of IVDD were found by radiological imaging, histology, or IHC in the 31G needle group or the vehicle group. By contrast, in the 0.5, 1, 2, and 4 μg AGEs groups, caudal IVDD was successfully established and the IVDD severity is increasing in a dose-dependent manner. Compared with the 2 μg AGEs group, rats in the non-ovariectomized group showed less IVDD, indicating the protective effect of endogenous estrogen on degenerative IVD. Conclusions:A single injection of AGEs to caudal discs can cause reliable and reproducible IVDD in ovariectomized female rats. Additionally, the endogenous estrogen might have a protective effect on the IVD to mitigate the degeneration.

This study aims to investigate whether Hounsfield unit (HU) value is correlated with intervertebral disc (IVD) degeneration (IVDD) by comparing premenopausal with menopausal women patients. A total of 101 female patients who underwent treatment in our hospital between February 2022 and February 2023 were retrospectively reviewed and included in this study. All patients were divided into either the premenopausal group or the menopausal group, according to age and menopause status. The changes in disc height index (DHI) on X-ray, the Hounsfield unit (HU) value on computed tomography (CT), and the area of the nucleus pulposus (NP) on magnetic resonance imaging (MRI) were assessed and compared between the two groups. There is a significant difference in the Pfirrmann grading of T12-S1 discs between the premenopausal and menopausal groups; the menopausal group has more degenerated discs compared with the premenopausal group (P < 0.001). There is no significant difference in DHI measurements between the premenopausal and menopausal groups. HU values in the premenopausal group are greater compared with the menopausal group from T12 to S1 vertebrae (all P < 0.001). Regarding the NP area on MRI, the L2-L3 IV disc space have a bigger area in the premenopausal group compared with the menopausal group (P = 0.029), with no significant difference in other IVD segments. The HU value on CT is significantly decreased with IVDD progression after menopause. The change in HU value could indirectly reflect vertebral bone mineral density. Therefore, the decline of estrogen after menopause leads to vertebral osteoporosis, which might contribute to IVDD progression.

This study aimed to compare the clinical efficacy and radiological results between unilateral pedicle screw fixation (UPSF) and bilateral pedicle screw fixation (BPSF) for treating two-level lumbar degenerative diseases. The study involved 106 patients with two-level lumbar degenerative diseases. In the UPSF group (n = 52), 28 underwent intervertebral fusion (IF), 17 underwent posterolateral fusion (PLF), and 7 underwent IF & PLF. In the BPSF group (n = 54), 43 underwent IF, 2 underwent PLF, and 9 underwent IF & PLF. The clinical efficacy and radiological data were evaluated and compared. The UPSF group was significantly lower than the BPSF group regarding operation time, intraoperative blood loss, and hospitalization expenses. Postoperative visual analog scale scores and oswestry disability index were significantly decreased in both groups compared with pre-surgery. At the last follow-up, the intervertebral disc height of the cranial adjacent segment decreased more in the UPSF group compared with the BPSF group. The incidence of screw loosening in the UPSF group was significantly higher compared with the BPSF group. Compared to BPSF, UPSF can achieve similar and satisfactory clinical efficacy for the treatment of two-level lumbar degenerative diseases with less operation time, muscle damage, blood loss, and hospitalization expenses. However, the occurrence of pedicle screw loosening was higher in the UPSF group.

ABSTRACTBackgroundChronic low back pain (LBP) is a significant global health concern, often linked to vertebral bone marrow lesions (BML), particularly fatty replacement (FR). This study aims to explore the relationship between the gut microbiome, serum metabolome, and FR in chronic LBP patients.MethodsSerum metabolomic profiling and gut microbiome analysis were conducted in chronic LBP patients with and without FR (LBP + FR, n = 40; LBP, n = 40) and Healthy Controls (HC, n = 31). The study investigates alterations in branched‐chain amino acids (BCAAs) levels and identifies key microbial species associated with BCAA metabolism. In vitro experiments elucidate the role of BCAAs in adipogenesis of bone marrow mesenchymal stem cells (BM‐MSCs) via the SIRT4 pathway.ResultsChronic LBP patients with FR exhibit depleted BCAA levels in their serum metabolome, along with alterations in the gut microbiome. Specific microbial species, including Ruminococcus gnavus, Roseburia hominis, and Lachnospiraceae bacterium 8 1 57FAA, are identified as influential in BCAA metabolism and BM‐MSCs metabolism. In vitro experiments demonstrate the ability of BCAAs to induce BM‐MSCs adipogenesis through SIRT4 pathway activation.ConclusionThis study sheds light on the intricate relationship between the disturbed gut ecosystem, serum metabolites, and FR in chronic LBP. Dysbiosis in the gut microbiome may contribute to altered BCAA degradation, subsequently promoting BM‐MSCs adipogenesis and FR. Understanding these interactions provides insights for targeted therapeutic strategies to mitigate chronic LBP associated with FR by restoring gut microbial balance and modulating serum metabolite profiles.

This study aims to analyse the effect of diabetes mellitus (DM) on the radiological changes of Magnetic Resonance Imaging (MRI) on the intervertebral discs and paravertebral muscle to investigate the effect of DM on spinal degeneration. This retrospective study initially included 262 patients who underwent treatment between January 2020 and December 2021 because of lumbar disc herniation. Amongst these patients, 98 patients suffered from type 2 diabetes mellitus (T2DM) for more than five years; this is the poorly controlled group (haemoglobin A1c (HbA1c) ≥ 6.5

EDITORIAL article Front. Cell Dev. Biol., 18 April 2024Sec. Molecular and Cellular Pathology Volume 12 - 2024 | https://doi.org/10.3389/fcell.2024.1401933

Sclerosing thoracic disc herniation refers to a condition in which the intervertebral disc in the thoracic region protrudes and becomes calcified, causing compression on the spinal cord and/or nerve roots. Sclerosing herniation of the thoracic disc poses a significant danger as it can lead to serious complications like paraplegia during or after surgery. Iatrogenic spinal cord injury is a common risk for individuals diagnosed with sclerosing thoracic disc herniation due to the inflexible protrusion of the sclerosing disc into the spinal canal and its adhesion to the ventral side of the dural sac. The challenging and crucial aspect of the surgery is how to safely and efficiently eliminate the hardened tissue. The eggshell method is a surgical procedure that addresses the kyphosis abnormality of the spinal column by excavating the vertebral body via the pedicles and subsequently inserting the kyphotic fracture block into the excavated vertebral body. In this article, a revised surgical method using the eggshell technique will be presented for the treatment of sclerosing thoracic disc herniation. The surgical procedure briefly involves hollowing out the anterior intervertebral space of the hardened disc tissue to create an eggshell-like structure, with the sclerotic tissue forming the posterior wall. Subsequently, the sclerotic disc tissue is pushed into the hollow intervertebral space to achieve complete decompression of the ventral spinal cord. The safety and effectiveness of this approach for treating sclerosing thoracic disc herniation have been confirmed.

Lower back pain is an extremely common medical issue in populations worldwide. One of the main contributors to lower back pain is intervertebral disc (IVD) degeneration. An ideal animal model of IVD degeneration is essential to study the pathophysiology of lower back pain and investigate potential therapeutic strategies. Rabbit models are reliable, economical, and easily established animal models. The retroperitoneal approach has been widely used to induce IVD degeneration in rabbit models. However, there are reported complications associated with this technique, such as the avulsion of segmental arteries and nerve root injury. In this paper, we aim to show a surgical protocol using needle puncture to establish rabbit lumbar disc degeneration via a transabdominal approach. Consequently, radiological checks and histological analyses indicated that lumbar disc degeneration was successfully established in rabbits. This surgical protocol presents the precise location of target discs and high reproducibility of IVD degeneration models with fewer complications.

This study aims to report a new distribution pattern of Modic changes (MCs) in patients with lumbar disc herniation (LDH) and investigate the prevalence, correlative factors and clinical outcomes of asymmetric Modic changes (AMCs). The study population consisted of 289 Chinese Han patients who were diagnosed with LDH and single-segment MCs from January 2017 to December 2019. Demographic, clinical and imagological information was collected. Lumbar MRI was performed to assess MCs and intervertebral discs. The visual analogue score (VAS) and Oswestry disability index (ODI) were evaluated in patients undergoing surgery preoperatively and at the final follow-up. Correlative factors contributing to AMCs were analysed by multivariate logistic regression. The study population included 197 patients with AMCs and 92 patients with symmetric Modic changes (SMCs). The incidence of leg pain (P < 0.001) and surgical treatment (P = 0.027) in the AMC group was higher than that in the SMC group. The VAS of low back pain was lower (P = 0.048), and the VAS of leg pain was higher (P = 0.036) in the AMC group than in the SMC group preoperatively. Multivariate logistic regression analysis revealed that leg pain (OR = 2.169, 95

Purpose To investigate the incidence and risk factors of lumbar plexus injury (LPI) after oblique lumbar interbody fusion (OLIF) surgery. Methods A total of 110 patients who underwent OLIF surgery between January 2017 and January 2021 were retrospectively reviewed. Patients were divided into two groups: the group with LPI (LPI group) and the group without LPI (non-LPI group). The baseline demographic data, surgical variables and radiographic parameters were compared and analyzed between these two groups. Results Among all participants, 13 (8.5%) had LPI-related symptoms postoperatively (short-term), and 6 (5.5%) did not fully recover after one year (long-term). Statistically, there were no significant differences in the baseline demographic data, surgery duration, intraoperative blood loss, preoperative diagnosis, surgical procedures used and incision length. Compared with the non-LPI group, patients in the LPI group had a narrower OLIF channel space. In LPI group, the anterior edge of left psoas major muscle overpasses the anterior edge of surgical intervertebral disk (IVD) on axial MRI. Logistic regression analysis revealed that narrow OLIF channel space and the anterior edge of left psoas major muscle overpassing the anterior edge of surgical IVD on axial MRI were independently associated with both short-term and long-term LPI. Conclusion Narrow OLIF channel space and the anterior edge of left psoas major muscle overpassing the anterior edge of surgical IVD are significant risk factors of OLIF surgery-related LPI. Surgeons should use preoperative imaging to adequately assess these risk factors to reduce the occurrence of LPI.

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Lumbar spine diseases often cause lower back pain, lower extremity pain, numbness, and paresthesia. In severe cases, intermittent claudication may occur, affecting the quality of life of patients. Surgery is often required when conservative treatment fails, or when patients' symptoms become unbearable. Surgical treatments include laminectomy and discectomy, as well as interbody fusion. The main purpose of laminectomy and discectomy is to relieve nerve compression; however, recurrence is common due to spinal instability. Interbody fusion improves stability while relieving nerve compression and significantly reduces the risk of recurrence compared to non -fusion surgery. Nonetheless, conventionally posterior intervertebral fusion requires separation of the muscles to expose the operated segment, which causes more trauma to the patient. In contrast, the oblique lateral interbody fusion (OLIF) technique achieves spinal fusion with minimal trauma to the patients and shortens the recovery time. This article introduces procedures of stand-alone OLIF surgery performed in the lumbar spine, providing a reference for other spine surgeons.

Lumbar spine diseases often cause lower back pain, lower extremity pain, numbness, and paresthesia. In severe cases, intermittent claudication may occur, affecting the quality of life of patients. Surgery is often required when conservative treatment fails, or when patients' symptoms become unbearable. Surgical treatments include laminectomy and discectomy, as well as interbody fusion. The main purpose of laminectomy and discectomy is to relieve nerve compression; however, recurrence is common due to spinal instability. Interbody fusion improves stability while relieving nerve compression and significantly reduces the risk of recurrence compared to non-fusion surgery. Nonetheless, conventionally posterior intervertebral fusion requires separation of the muscles to expose the operated segment, which causes more trauma to the patient. In contrast, the oblique lateral interbody fusion (OLIF) technique achieves spinal fusion with minimal trauma to the patients and shortens the recovery time. This article introduces procedures of stand-alone OLIF surgery performed in the lumbar spine, providing a reference for other spine surgeons.