Articular cartilage repair biomaterials: strategies and applications.

Articular cartilage injury is a frequent worldwide disease, while effective treatment is urgently needed. Due to lack of blood vessels and nerves, the ability of cartilage to self-repair is limited. Despite the availability of various clinical treatments, unfavorable prognoses and complications remain prevalent. However, the advent of tissue engineering and regenerative medicine has generated considerable interests in using biomaterials for articular cartilage repair. Nevertheless, there remains a notable scarcity of comprehensive reviews that provide an in-depth exploration of the various strategies and applications. Herein, we present an overview of the primary biomaterials and bioactive substances from the tissue engineering perspective to repair articular cartilage. The strategies include regeneration, substitution, and immunization. We comprehensively delineate the influence of mechanically supportive scaffolds on cellular behavior, shedding light on emerging scaffold technologies, including stimuli-responsive smart scaffolds, 3D-printed scaffolds, and cartilage bionic scaffolds. Biologically active substances, including bioactive factors, stem cells, extracellular vesicles (EVs), and cartilage organoids, are elucidated for their roles in regulating the activity of chondrocytes. Furthermore, the composite bioactive scaffolds produced industrially to put into clinical use, are also explicitly presented. This review offers innovative solutions for treating articular cartilage ailments and emphasizes the potential of biomaterials for articular cartilage repair in clinical translation.

M2 macrophage-derived exosomes promote diabetic fracture healing by acting as an immunomodulator.

Diabetes mellitus is a chronically inflamed disease that predisposes to delayed fracture healing. Macrophages play a key role in the process of fracture healing by undergoing polarization into either M1 or M2 subtypes, which respectively exhibit pro-inflammatory or anti-inflammatory functions. Therefore, modulation of macrophage polarization to the M2 subtype is beneficial for fracture healing. Exosomes perform an important role in improving the osteoimmune microenvironment due to their extremely low immunogenicity and high bioactivity. In this study, we extracted the M2-exosomes and used them to intervene the bone repair in diabetic fractures. The results showed that M2-exosomes significantly modulate the osteoimmune microenvironment by decreasing the proportion of M1 macrophages, thereby accelerating diabetic fracture healing. We further confirmed that M2-exosomes induced the conversion of M1 macrophages into M2 macrophages by stimulating the PI3K/AKT pathway. Our study offers a fresh perspective and a potential therapeutic approach for M2-exosomes to improve diabetic fracture healing.

Earlier or heavier spinal loading is more likely to lead to recurrent lumbar disc herniation after percutaneous endoscopic lumbar discectomy.

PURPOSE: To evaluate the clinical features of and risk factors for recurrent lumbar disc herniation (rLDH) after percutaneous endoscopic lumbar discectomy (PELD) in our clinical practice. METHODS: A total of 942 consecutive patients who underwent single-level PELD from January 2013 to August 2019 were included. Patients were divided into the recurrence group and the nonrecurrence group. Patient characteristics, radiographic parameters and surgical variables were compared between the two groups. Univariate analysis and multiple logistic regression analysis were adopted to determine the risk factors for recurrence after PELD. RESULTS: The prevalence of rLDH was 6.05%. Age, sex, tobacco use, duration of low back pain, body mass index (BMI), occupational lifting, herniated disc type, facet joint degeneration, operation time and time to ambulation were significantly different between the two groups. Univariate analysis showed that age (P < 0.001), sex (P = 0.019), BMI (P = 0.001), current smoking (P < 0.001), occupational lifting (P < 0.001), facet joint degeneration (P = 0.001), operation time (P = 0.002), and time to ambulation (P < 0.001) could be significantly associated with the incidence of rLDH after PELD. Multivariate analysis suggested that an older age (P < 0.001), the male sex (P = 0.017), a high BMI (P < 0.001), heavy work (P = 0.003), grade II facet joint degeneration (P < 0.001) and early ambulation (P < 0.001) were significantly related to rLDH after PELD. CONCLUSIONS: An older age, the male sex, a higher BMI, heavy work, grade II facet joint degeneration, and early ambulation are independent significant risk factors for rLDH after PELD. Great importance should be attached to these risk factors to prevent rLDH. We suggest that patients control their weight, avoid heavy work, ambulate at an appropriate time, and perform strengthening rehabilitation exercises to reduce the incidence of rLDH.

Increased expression of Siglec-1 on peripheral blood monocytes and its role in mononuclear cell reactivity to autoantigen in rheumatoid arthritis.

OBJECTIVES: Elevated expression of Siglec-1 on circulating monocytes has been reported in some inflammatory and autoimmune diseases, but its expression and role in RA has not been elucidated. The aims of this study were to determine the expression of Siglec-1 in peripheral blood and to explore its role in mononuclear cell reactivity to autoantigen in RA. METHODS: Siglec-1 protein and mRNA levels in 42 RA patients, 39 OA patients, 28 SLE patients and 42 normal controls were determined by flow cytometry and quantitative RT-PCR, respectively. In addition, 10 patients with active RA received DMARDs for 12 weeks and the frequencies of Siglec-1-positive cells and the 28-joint DAS (DAS28) were assessed before and after therapy. Furthermore, TNF-α, IFN-γ and type II collagen were used to up-regulate Siglec-1. Peripheral blood mononuclear cells (PBMCs) from different groups were stimulated with mitogens or antigens and cell proliferation and cytokine production were determined. RESULTS: The protein and mRNA levels of Siglec-1 on PBMCs and monocytes in RA patients were significantly higher than those in OA patients and healthy controls. Moreover, the expression of Siglec-1 protein on PBMCs was positively correlated with DAS28, ESR, high-sensitivity CRP and IgM-RF, but not with anti-CCP antibody. Interestingly, Siglec-1 expression was decreased in parallel with the decrease in the DAS28 after 12 weeks of anti-rheumatic treatment. Furthermore, TNF-α, IFN-γ and type II collagen can up-regulate Siglec-1 in PBMCs. Elevated PBMC proliferation and proinflammatory cytokine production to collagen stimulation in RA patients decreased when Siglec-1 was inhibited by anti-Siglec-1 antibodies. CONCLUSION: Elevated Siglec-1 expression in PBMCs and monocytes can potentially serve as a biomarker for monitoring disease activity in RA. Siglec-1 may also play a proinflammatory role in stimulating lymphocyte proliferation and activation in RA.

Contribution of monocytes Siglec-1 in stimulating T cells proliferation and activation in atherosclerosis.

OBJECTIVE: Atherosclerosis (AS) is widely accepted as an inflammatory disease and monocytes are particularly important in inflammatory immune responses. As an important biomarker of monocytes activation, Siglec-1 is highly expressed on circulating monocytes and atherosclerotic plaques of coronary artery disease (CAD) patients, but the exact role of Siglec-1 has not been elucidated. METHODS: M-CSF, INF-α, IFN-γ, TNF-α and ox-LDL alone or in combination were used to stimulate Siglec-1 expression on monocytes, whereas small interfering RNA (si-RNA) or blocking antibody was used to down-regulate Siglec-1. Meanwhile, the role of Siglec-1 in chemokines secretion was determined. Then monocytes from CAD patients or healthy controls were cocultured with CD4+ or CD8+ T cells from a third healthy individual, and lymphocyte proliferation and activation were determined. RESULTS: All the stimuluses could enhance Siglec-1 expression on monocytes in a dose-dependent manner, and M-CSF could synergistically stimulate Siglec-1 expression with ox-LDL. Moreover, the secretion of MCP-1, MIP-1α and MIP-2 were enhanced when Siglec-1 was up-regulated and down to normal level when Siglec-1 was blocked. More importantly, increased Siglec-1 expression on monocytes was related to the increased T cell proliferation and pro-inflammatory cytokines secretion in CAD patients. However, down-regulation of Siglec-1 could attenuate proliferation and activation of cocultured CD4+ and CD8+ T cells. CONCLUSION: Siglec-1 can promote chemokines and pro-inflammatory cytokines secretion and influence the inflammatory process of AS.

A comparison of anterior cervical discectomy and corpectomy in patients with multilevel cervical spondylotic myelopathy.

BACKGROUND: The optimal surgical approach for multilevel cervical spondylotic myelopathy (CSM) has not been defined, and the relative merits of multilevel anterior cervical discectomy and fusion (ACDF) and anterior cervical corpectomy (2-level or skip 1-level corpectomy) and fusion (ACCF) remain controversial. However, few comparative studies have been conducted on these two surgical approaches. METHODS: This study retrospectively reviewed the case histories of 120 patients that underwent surgical treatment for 3- or 4-level CSM from July 2003 to June 2008. One hundred and twenty patients (81 male and 39 female) of mean age 58.3±9.8 years (37-78) were included. The study compared perioperative parameters (blood loss, operation times), complications [surgery-related complications (CSF, hoarseness, epidural hematoma, C5-palsy, dysphagia), instrumentation and graft related complications (dislodgement, subsidence)], clinical parameters [Japanese Orthopedic Association (JOA) scores, Neck Dysfunciton Index (NDI) scores], and radiologic parameters (segmental lordosis, fusion rate). RESULTS: At a minimum of 2-year follow-up, both ACDF and ACCF groups demonstrated a significant increase in the JOA scores (preoperatively 9.25±1.9 and 8.86±1.9, postoperatively 13.86±1.6 and 13.27±1.8, respectively), segmental lordosis (preoperatively 9.79±3.4 and 9.54±3.0, postoperatively 17.75±2.6 and 14.49±2.5, respectively) and NDI scores (preoperatively 12.56±3.0 and 12.21±3.4, postoperatively 3.44±1.7 and 5.68±2.6, respectively). Six patients (2 dislodgement, 4 subsidence) in ACCF group had instrumentation and graft related-complications and they had no obvious neurological symptoms without a second operation. Blood loss (102.81±51.3 and 149.05±74, respectively, P=0.000), NDI scores (P=0.000), and instrumentation and graft related-complications (P=0.032) were significantly lower in the ACDF group, whereas operation time (138.07±30.9 and 125.08±26.4, respectively, P=0.021) and segmental lordosis (P=0.000) were significantly greater in the ACDF group. Other parameters were not significantly different in the two groups. CONCLUSIONS: Surgical managements of 3- or 4-level CSM by ACDF or ACCF showed no significant differences in terms of achieved clinical symptom improvements, with the exception of better postoperative NDI scores in ACDF. In addition, ACDF is better than ACCF in terms of blood loss, lordotic curvature improvement and instrumentation and graft related-complication rates, with the exception of operation times.

A comparison of the Gallie technique and casting versus the harms technique for the treatment of odontoid fractures.

OBJECTIVE: The objective of this study was to compare perioperative, clinical parameters, complications, and reoperation rate of the Gallie technique and head-neck-chest plaster with the Harms technique in the treatment of odontoid fractures. DESIGN: A retrospective study. SETTING: Level I spine center. PATIENTS: Fifty-seven patients with odontoid fractures treated either with the Gallie technique and casting or the Harms technique between July 2002 and June 2008. INTERVENTION: Surgery. MAIN OUTCOME MEASUREMENTS: At a minimum of 2-year follow-up, comparison of the two groups was conducted in terms of hospital stay, blood loss, operation time, cost of the first admission, total cost, time to fusion, time to return to previous occupation, Japanese Orthopedic Association scores, visual analog scale scores of neck pain, complications (nonunion, delayed union, hardware breakage, wound infection), and reoperation rate. RESULTS: There were no significant differences in terms of hospital stay, time to fusion, Japanese Orthopedic Association scores, neck pain visual analog scale scores, complications, or reoperation rate between the two groups. Blood loss, operation time, cost of the first admission, and total cost were significantly lower in the Gallie group than that in the Harms group. However, the Gallie group took longer to return to previous occupation than the Harms group (P < 0.001). CONCLUSIONS: Management of odontoid fractures by either the Gallie technique and casting or the Harms technique was found to be similar in clinical outcomes. Although the Harms technique was associated with more blood loss, operation time, and cost, the Harms technique was found to be superior to the Gallie technique with casting in terms of time to return to previous occupation.

Paresis associated with aconuresis caused by intervertebral disc calcification at c7-t1: a case report and review of the literature.

STUDY DESIGN: Case report. OBJECTIVE: To report a case of a 19-year-old boy with intervertebral disc calcification (IDC) at C7-T1, who presented with paresis and aconuresis. Surgical outcome was assessed. SUMMARY OF BACKGROUND DATA: IDC, commonly seen in the cervical spine region in children, is well-known as a self-limiting disorder with no or little symptoms. Surgical intervention is usually not required. METHODS: A 19-year-old boy presented with acute back pain, progressive numbness, and weakness of both lower extremities and aconuresis for 1 week. There was no traumatic history or signs of infection. Radiograph, computed tomography with reconstruction, and magnetic resonance imaging revealed C7-T1 IDC with severe spinal cord compression. Decompression with anterior cervical corpectomy and fusion was performed. RESULTS: Follow-up showed complete resolution of the back pain and complete recovery of motor power and sensory function in both lower extremities and return of normal micturition function. The patient had full recovery with no complications. CONCLUSION: Serious neurologic deficit, especially a bladder dysfunction, caused by calcified intervertebral disc is rare. However, favorable outcome can be achieved in those cases where rapid diagnosis is made and followed by spinal cord decompression.