Highly oriented hydrogels for tissue regeneration: design strategies, cellular mechanisms, and biomedical applications.

Many human tissues exhibit a highly oriented architecture that confers them with distinct mechanical properties, enabling adaptation to diverse and challenging environments. Hydrogels, with their water-rich "soft and wet" structure, have emerged as promising biomimetic materials in tissue engineering for repairing and replacing damaged tissues and organs. Highly oriented hydrogels can especially emulate the structural orientation found in human tissue, exhibiting unique physiological functions and properties absent in traditional homogeneous isotropic hydrogels. The design and preparation of highly oriented hydrogels involve strategies like including hydrogels with highly oriented nanofillers, polymer-chain networks, void channels, and microfabricated structures. Understanding the specific mechanism of action of how these highly oriented hydrogels affect cell behavior and their biological applications for repairing highly oriented tissues such as the cornea, skin, skeletal muscle, tendon, ligament, cartilage, bone, blood vessels, heart, etc., requires further exploration and generalization. Therefore, this review aims to fill that gap by focusing on the design strategy of highly oriented hydrogels and their application in the field of tissue engineering. Furthermore, we provide a detailed discussion on the application of highly oriented hydrogels in various tissues and organs and the mechanisms through which highly oriented structures influence cell behavior.

Non-stem cell-derived exosomes: a novel therapeutics for neurotrauma.

Neurotrauma, encompassing traumatic brain injuries (TBI) and spinal cord injuries (SCI) impacts a significant portion of the global population. While spontaneous recovery post-TBI or SCI is possible, recent advancements in cell-based therapies aim to bolster these natural reparative mechanisms. Emerging research indicates that the beneficial outcomes of such therapies might be largely mediated by exosomes secreted from the administered cells. While stem cells have garnered much attention, exosomes derived from non-stem cells, including neurons, Schwann cells, microglia, and vascular endothelial cells, have shown notable therapeutic potential. These exosomes contribute to angiogenesis, neurogenesis, and axon remodeling, and display anti-inflammatory properties, marking them as promising agents for neurorestorative treatments. This review provides an in-depth exploration of the current methodologies, challenges, and future directions regarding the therapeutic role of non-stem cell-derived exosomes in neurotrauma.

Biomedical applications of stimuli-responsive "smart" interpenetrating polymer network hydrogels.

In recent years, owing to the ongoing advancements in polymer materials, hydrogels have found increasing applications in the biomedical domain, notably in the realm of stimuli-responsive "smart" hydrogels. Nonetheless, conventional single-network stimuli-responsive "smart" hydrogels frequently exhibit deficiencies, including low mechanical strength, limited biocompatibility, and extended response times. In response, researchers have addressed these challenges by introducing a second network to create stimuli-responsive "smart" Interpenetrating Polymer Network (IPN) hydrogels. The mechanical strength of the material can be significantly improved due to the topological entanglement and physical interactions within the interpenetrating structure. Simultaneously, combining different network structures enhances the biocompatibility and stimulus responsiveness of the gel, endowing it with unique properties such as cell adhesion, conductivity, hemostasis/antioxidation, and color-changing capabilities. This article primarily aims to elucidate the stimulus-inducing factors in stimuli-responsive "smart" IPN hydrogels, the impact of the gels on cell behaviors and their biomedical application range. Additionally, we also offer an in-depth exposition of their categorization, mechanisms, performance characteristics, and related aspects. This review furnishes a comprehensive assessment and outlook for the advancement of stimuli-responsive "smart" IPN hydrogels within the biomedical arena. We believe that, as the biomedical field increasingly demands novel materials featuring improved mechanical properties, robust biocompatibility, and heightened stimulus responsiveness, stimuli-responsive "smart" IPN hydrogels will hold substantial promise for wide-ranging applications in this domain.

Dual aldehyde cross-linked hyaluronic acid hydrogels loaded with PRP and NGF biofunctionalized PEEK interfaces to enhance osteogenesis and vascularization.

Polyetheretherketone (PEEK) material has become a potential bone replacement material due to its elastic modulus, which is close to that of human bone, and stable chemical properties. However, its biological inertness has hindered its clinical application. To improve the biological inertia of PEEK material, a hyaluronic acid (HA) hydrogel coating loaded with platelet-rich plasma (PRP) and nerve growth factor (NGF) was constructed on the surface of PEEK material in this study. After the hybrid hydrogel coating was constructed, scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), Fourier transform infrared spectroscopy (FT-IR), degradation tests, and enzyme-linked immunosorbent assays (ELISAs) were used to evaluate its characteristics and biological properties. The osteogenic and angiogenic potentials were also investigated in vitro and in vivo. Our results showed that the HA hydrogel loaded with RPP and NGF on the PEEK surface degraded slowly and could sustainably release various growth factors, including NGF. The results of in vitro tests showed that the hybrid hydrogel on the surface of PEEK effectively promoted osteogenesis and angiogenesis. The in vivo experiment also confirmed that the PEEK surface hydrogel could promote osseointegration of the implant and the integration of new bone and neovascularization. Our results suggest that the cross-linked hyaluronic acid hydrogel loaded with PRP and NGF can significantly improve the biological inertia of PEEK material, endowing PEEK material with good osteogenic and angiogenic ability.

Comparative Effects of Different Epidural Injection Approaches on Lumbosacral Radicular Pain: A Systematic Review and Network Meta-analysis.

BACKGROUND: Lumbar disc herniation (LDH) is the main cause of low back pain and/or radiculopathy. Currently, epidural intervention is a widely used and effective conservative treatment method for managing low back and radicular pain caused by LDH. OBJECTIVES: To explore the effectiveness of different epidural injection approaches in adult patients with lumbosacral radicular pain. STUDY DESIGN: Systematic review and network meta-analysis (NMA). METHODS: An electronic literature search was performed in the Pubmed, Embase, Cochrane Library, and Web of Science databases. Two authors independently performed data extraction and quality assessment. A Bayesian random effects model was conducted to incorporate the estimates of direct and indirect treatment comparisons and rank the interventions in order. Effect estimates from Bayesian NMA were presented as mean difference (MD) with 95% credible intervals (CrI). RESULTS: This NMA assessed caudal (C), interlaminar (IL), transforaminal (TF) and parasagittal interlaminar (PIL) epidural injection approaches for lumbosacral radicular pain from 7 trials. A statistically significant treatment difference for pain relief was reported for midline interlaminar (MIL) vs PIL (MD, 1.16; 95%CrI, 0.31-2.06), MIL vs TF (MD, 1.12; 95%CrI, 0.51-1.85), C vs TF (MD, 1.07; 95%CrI, 0.01-2.18) in short-term follow-up and MIL vs TF (MD, 1.8; 95% CrI, 0.3-3.48) in intermediate-term follow-up. For functional improvement, a statistically significant difference was observed with MIL vs PIL (MD, 9.9; 95% CrI, 0.64-19.94) and MIL vs TF (MD, 1.08; 95% CrI, 1.08-17.08) in short-term follow-up. Moreover, the PIL approach and TF appeoach were ranked in the top 2 for pain relief and functional improvement, both in short-term and intermediate-term follow-up. LIMITATIONS: 1) The number of studies included was small; 2) some treatments lacked direct comparisons; 3) only scores from the visual analog scale for pain and the Oswestry Disability Index were included in the result; 4) important outcomes, such as complications, were not included. CONCLUSION: In short-term and intermediate-term follow-up, the PIL approach has the highest probability for pain relief and functional improvement.

Comparative efficacy of radiofrequency denervation in chronic low back pain: A systematic review and network meta-analysis.

Background: Facet joint pain is a common cause of chronic low back pain (CLBP). Radiofrequency (RF) denervation is an effective treatment option. Purpose: A systematic review and network meta-analysis (NMA) was performed to evaluate and compare the efficacy and effectiveness of different RF denervation treatments in managing facet joint-derived CLBP. Methods: The Cochrane Library, Embase, PubMed, and China Biology Medicine were searched to identify eligible randomized controlled trials (RCTs) from January 1966 through December 2021. Interventions included conventional radiofrequency denervation (CRF), pulsed radiofrequency denervation (PRF), pulsed radiofrequency treatment of the dorsal root ganglia (PRF-DRG), radiofrequency facet capsule denervation (RF-FC), and radiofrequency ablation under endoscopic guidance (ERFA). The outcome was the mean change in visual analog scale (VAS) score from baseline. A random-effects NMA was used to compare the pain relief effects of the interventions over the short term (≤6 months) and long term (12 months). The rank of effect estimation for each intervention was computed using the surface under the cumulative ranking curve. Results: A total of 10 RCTs with 715 patients met the inclusion criteria. Moderate evidence indicated that CRF denervation had a greater effect on pain relief than sham control in the short term (standardized mean difference (SMD) -1.58, 95% confidence intervals (CI) -2.98 to -0.18) and the long term (SMD -4.90, 95% CI, -5.86 to -3.94). Fair evidence indicated that PRF denervation was more effective than sham control for pain over the long term (SMD -1.30, 95% CI, -2.17 to -0.43). Fair evidence showed that ERFA denervation was more effective for pain relief than sham control in the short term (SMD -3.07, 95% CI, -5.81 to -0.32) and the long term (SMD -4.00, 95% CI, -4.95 to -3.05). Fair evidence showed that RF-FC denervation was more effective for pain relief than sham control in the long term (SMD -1.11, 95% CI, -2.07 to -0.15). A fair level of evidence indicated that PRF-DRG denervation was more effective for pain relief than sham control in the short term (SMD -5.34, 95% CI, -8.30 to -2.39). Conclusion: RF is an effective option for patients diagnosed with facet joint-derived CLBP.Systematic Review Registration: Identifier: CRD42022298238.

A Retrospective Comparative Study of Modified Percutaneous Endoscopic Transforaminal Discectomy and Open Lumbar Discectomy for Gluteal Pain Caused by Lumbar Disc Herniation.

Introduction: This study aimed to demonstrate the safety and effectiveness of modified percutaneous endoscopic transforaminal discectomy (PETD) in the surgical management of single-segment lumbar disc herniation (LDH) gluteal pain and to determine whether it provides a better clinical outcome than open lumbar discectomy (OD). Methods: A retrospective analysis of patients treated with modified PETD and OD for gluteal pain in LDH from January 2015 to December 2020 was conducted. Sample size was determined using a priori power analysis. Demographic information, surgical outcomes including procedure time (minutes), intraoperative blood loss (mL), hospital days, costs (RMB), fluoroscopy shots, recurrence and complications, etc., were recorded and analyzed. Prognostic outcomes were assessed using the visual analog scale (VAS), the Oswestry Disability Index (ODI), the Japanese Orthopedic Association Score (JOA) and modified MacNab criteria. The preoperative and postoperative VAS, ODI and JOA scores were recorded by two assistants. When the results were inconsistent, the scores were recorded again by the lead professor until all scores were consistently recorded in the data. MRI was used to assess radiological improvement and all patients received follow-ups for at least one year. Results: The sample size required for the study was calculated by a priori analysis, and a total of 72 participants were required for the study to achieve 95% statistical test power. A total of 93 patients were included, 47 of whom underwent modified PETD, and 46 of whom underwent OD. In the modified PETD intragroup comparison, VAS scores ranged from 7.14 ± 0.89 preoperatively to 2.00 ± 0.58, 2.68 ± 0.70, 2.55 ± 0.69, 2.23 ± 0.81, and 1.85 ± 0.72 at 7 days, 1 month, 3 months, 6 months, and 12 months postoperatively. Patients showed significant pain relief postoperatively (P < 0.01). According to the modified MacNab score, the excellent rate in the PETD group was 89.36%. There was no significant difference compared to the OD group (89.13%, P > 0.05). Complication rates were lower (P > 0.05) but recurrence rates were higher (P > 0.05) in the modified PETD group than in the OD group. The modified PETD group had a faster operative time (P < 0.01), shorter hospital stay (P < 0.01), less intraoperative bleeding (P < 0.01), and less financial burden to the patient (P < 0.01) than the OD group. At 7 days postoperatively, the VAS score for low back pain was higher in the OD group than in the modified PETD group (P < 0.01). The VAS and JOA scores at 1, 3, 6, and 12 months postoperatively were not significantly different between the modified PETD and OD groups (P > 0.05), and the ODI was significantly different at 3 months postoperatively (P < 0.05). Conclusion: Modified PETD treatment is safe and effective for gluteal pain due to L4/5 disc herniation and has the advantages of a lower complication rate, faster postoperative recovery, shorter length of stay, fewer anesthesia risks and lower cost of the procedure compared with OD. However, modified PETD has a higher recurrence rate.

Corrigendum: Comparative Analysis of the Biomechanics Characteristics After Different Minimally Invasive Surgeries for Cervical Spondylopathy: A Finite Element Analysis.

[This corrects the article DOI: 10.3389/fbioe.2021.772853.].

Transforaminal endoscopic excision of bi-segmental non-communicating spinal extradural arachnoid cysts: A case report and literature review.

BACKGROUND: Spinal extradural arachnoid cysts (SEACs) are a rare cause of spinal cord compression. Typically, these cysts communicate with the intradural subarachnoid space through a small defect in the dural sac. For symptomatic SEACs, the standard treatment is to remove the cyst in total with a (hemi)laminectomy or laminoplasty. We present a rare case of bi-segmental non-communicating SEACs and describe our experience of using an endoscopic minimal access technique to remove bi-segmental non-communicating SEACs. CASE SUMMARY: A 79-year-old female presented with pain related to bi-segmental SEACs at the T11-L1 segments. She underwent sequential transforaminal percutaneous endoscopic thoracic cystectomy of the SEACs. Following her first procedure, spinal magnetic resonance imaging demonstrated complete excision of the cyst at the T12-L1 segment. However, the cyst at the T11-T12 segment was still present. Thus, a second procedure was performed to remove this lesion. The patient's right-sided lumbar and abdominal pain improved significantly postoperatively. Her Japanese Orthopaedic Association score increased from 11 to 25, her visual analogue scale score was reduced from 8 to 1. The physical and mental component summary of the 36-item short-form health survey (SF-36) were 15.5 and 34.375 preoperatively, and had increased to 79.75 and 77.275 at the last follow-up visit, respectively. CONCLUSION: Bi-segmental non-communicating SEACs are extremely rare. Endoscopic surgery is a safe, effective, and reliable method for treating these cysts. In the event of bi-segmental SEACs, it is important to identify whether both cysts are communicating before surgery, and if not, to remove both cysts separately during the index surgery to avoid re-operation.

Effectiveness of platelet-rich plasma injections for the treatment of acute Achilles tendon rupture: A systematic review and meta-analysis.

BACKGROUND: The effect of platelet-rich plasma (PRP) on patients with acute Achilles tendon rupture is still controversial. The purpose of this systematic review is to assess the efficacy of PRP injections treating acute Achilles tendon rupture. METHODS: A comprehensive electronic literature search was performed in the PubMed, Embase, Cochrane Library, and Web of Science databases to identify relevant studies that were published prior to April 29, 2021. Randomized controlled trials evaluating the efficacy of PRP injections in treating patients with acute Achilles tendon rupture were included. Statistical analyses were conducted using RevMan software. RESULTS: Five randomized controlled trials were included in this systematic review. The results of the meta-analysis showed that PRP has positive effects on ankle dorsiflexion angle, dorsal extension strength of the ankle, and calf circumference compared with that in controls. However, the current evidence failed to show that PRP effectively improves ankle plantar flexion angle, plantar flexion strength of the ankle, and pain. CONCLUSIONS: PRP injections for the treatment of acute Achilles tendon rupture significantly improved ankle dorsiflexion angle, dorsal extension strength of the ankle, and calf circumference compared with that in controls. Additional studies with larger sample sizes, more rigorous designs and standardized protocols are needed to draw more reliable and accurate conclusions.

Zina percutaneous screw fixation combined with endoscopic lumbar intervertebral fusion under intraoperative neuromonitoring: A case report.

INTRODUCTION: Traditional open discectomy and intervertebral fusion surgery is the common strategy for lumbar disc herniation (LDH). However, it has the disadvantages of long recovery time and severe paravertebral soft tissue injury. Zina percutaneous screw fixation combined with endoscopic lumbar intervertebral fusion (ZELIF), as a novel minimally invasive surgical technique for LDH, has the advantages in quicker recovery, less soft tissue destruction, shorter hospital stays and less pain. We report a novel technique of ZELIF under intraoperative neuromonitoring (INM) for the treatment of LDH. PATIENT CONCERNS: A 51-year-old male presented to our hospital with left lower extremity pain and numbness for 1 year. DIAGNOSIS: Lumbar disc herniation (LDH). INTERVENTIONS: This patient was treated with Zina percutaneous screw fixation combined with endoscopic neural decompression, endplate preparation, and intervertebral fusion through Kambin's triangle. Each step of the operation was performed under INM. OUTCOMES: The follow-up period lasted 12 months; the hospitalization lasted 4 nights; the blood loss volume was 65 ml, and the time of operation was 266 min. INM showed no neurological damage during the surgery. No surgical complications, including neurological deterioration, cage migration, non-union, instrumentation failure or revision operation, were observed during the follow-up period. Visual Analogue Scale (VAS) score reduced from 7 to 1; the Oswestry Disability Index (ODI) decreased from 43 to 14; the EQ-5D score was 10 preoperatively and 15 at the final follow-up visit; the Physical Component Summary of the 36-Item Short Form Health Survey (SF-36) was 48 preoperatively and 49 at the last follow up visit; the SF-36 Mental Component Summary was 47 before surgery and decreased to 41 postoperatively. CONCLUSION: ZELIF under INM may represent a feasible, safe and effective alternative to endoscopic intervertebral fusion and percutaneous screw fixation, for decompressing the lumbar's exiting nerve root directly with minimal invasion in selected patients.

Comparative Analysis of the Biomechanical Characteristics After Different Minimally Invasive Surgeries for Cervical Spondylopathy: A Finite Element Analysis.

Minimally invasive surgeries, including posterior endoscopic cervical foraminotomy (PECF), microsurgical anterior cervical foraminotomy (MACF), anterior transdiscal approach of endoscopic cervical discectomy (ATd-ECD), and anterior transcorporeal approach of endoscopic cervical discectomy (ATc-ECD), have obtained positive results for cervical spondylotic radiculopathy. Nonetheless, there is a lack of comparison among them regarding their biomechanical performance. The purpose of this study is to investigate the biomechanical changes of operated and adjacent segments after minimally invasive surgeries compared to a normal cervical spine. A three-dimensional model of normal cervical vertebrae C3-C7 was established using finite element analysis. Afterwards, four surgical models (PECF, MACF, ATd-ECD, and ATc-ECD) were constructed on the basis of the normal model. Identical load conditions were applied to simulate flexion, extension, lateral bending, and axial rotation of the cervical spine. We calculated the range of motion (ROM), intradiscal pressure (IDP), annulus fibrosus pressure (AFP), uncovertebral joints contact pressure (CPRESS), and facet joints CPRESS under different motions. For all circumstances, ATc-ECD was close to the normal cervical spine model, whereas ATd-ECD significantly increased ROM and joints CPRESS and decreased IDP in the operated segment. PECF increased more the operated segment ROM than did the MACF, but the MACF obtained maximum IDP and AFP. Except for ATc-ECD, the other models increased joints CPRESS of the operated segment. For adjacent segments, ROM, IDP, and joints CPRESS showed a downward trend in all models. All models showed good biomechanical stability. With their combination biomechanics, safety, and conditions of application, PECF and ATc-ECD could be appropriate choices for cervical spondylotic radiculopathy.