Scar Tissue Formation Research Articles

A Case of Myelopathy Due to Fibrous Scar Tissue Formation around the Lead of Spinal Cord Stimulation Placed in Cervical Portion

A Case of Myelopathy Due to Fibrous Scar Tissue Formation around the Lead of Spinal Cord Stimulation Placed in Cervical Portion

Automatic in situ short-distance deposition of PLGA/PLLA composite nanofibrous membranes for personalized wound dressings.

Improving the mechanical properties of wound dressings and achieving personalized automatic real-time in situ deposition are important for accelerating wound management and repair. In this study, we report a self-designed automatic in situ deposition device based on solution blow spinning (SBS) to prepare poly(lactic-co-glycolic acid) (PLGA) and poly-L-lactic acid (PLLA) composite (PLGA/PLLA) nanofibrous membranes for wound dressing at a short distance. Polymer solution and in situ deposition conditions, including air pressure, spinning distance, solvent extrusion rate, and spinning rate, were optimized using orthogonal experiments and characterized via dynamic mechanical analysis. The microscopic morphology and physical properties of the prepared PLGA/PLLA composite nanofibrous membranes show that their strength, adhesion, water vapor transmission rate (WVTR), water retention, water absorption, degradation, and other properties were sufficient for wound-dressing applications. To investigate the possibility of a biomedical wound-dressing material, tannic acid (TA) was incorporated into the PLGA/PLLA composite nanofibrous membranes. The resultant PLGA/PLLA/TA composite nanofibrous membranes exhibited good biocompatibility and exceptional antibacterial properties against both Escherichia coli and Staphylococcus aureus. A pilot animal study illustrated the potential of this in situ deposition of PLGA/PLLA/TA composite nanofibrous membranes across multiple applications in wound healing/repair by reducing wound scar tissue formation and fibroblast overactivation.

AdipoRon reduces TGFβ1-mediated collagen deposition in vitro and alleviates knee stiffness in vivo.

Arthrofibrosis, which causes joint motion restrictions, is a common complication following total knee arthroplasty (TKA). Key features associated with arthrofibrosis include myofibroblast activation, knee stiffness, and excessive scar tissue formation. We previously demonstrated that adiponectin levels are suppressed within the knee tissues of patients affected by arthrofibrosis and showed that AdipoRon, an adiponectin receptor agonist, exhibited anti-fibrotic properties in human mesenchymal stem cells. In this study, the therapeutic potential of AdipoRon was evaluated on TGFβ1-mediated myofibroblast differentiation of primary human knee fibroblasts and in a mouse model of knee stiffness. Picrosirius red staining revealed that AdipoRon reduced TGFβ1-induced collagen deposition in primary knee fibroblasts derived from patients undergoing primary TKA and revision TKA for arthrofibrosis. AdipoRon also reduced mRNA and protein levels of ACTA2, a key myofibroblast marker. RNA-seq analysis corroborated the anti-myofibrogenic effects of AdipoRon. In our knee stiffness mouse model, 6 weeks of knee immobilization, to induce a knee contracture, in conjunction with daily vehicle (DMSO) or AdipoRon (1, 5, and 25 mg/kg) via intraperitoneal injections were well tolerated based on animal behavior and weight measurements. Biomechanical testing demonstrated that passive extension angles (PEAs) of experimental knees were similar between vehicle and AdipoRon treatment groups in mice evaluated immediately following immobilization. Interestingly, relative to vehicle-treated mice, 5 mg/kg AdipoRon therapy improved the PEA of the experimental knees in mice that underwent 4 weeks of knee remobilization following the immobilization and therapy. Together, these studies revealed that AdipoRon may be an effective therapeutic modality for arthrofibrosis.

Wound healing after therapy of oral potentially malignant disorders with a 445-nm semiconductor laser: a randomized clinical trial

ObjectivesOral potentially malignant disorders (OPMDs) are the most clinically relevant precursor lesions of the oral squamous cell carcinoma (OSCC). OSCC is one of the 15 most common cancers worldwide. OSCC is with its high rate of mortality an important cause of death worldwide. The diagnosis and therapy of clinically relevant precursor lesions of the OSCC is one of the main parts of prevention of this malignant disease. Targeted therapy is one of the main challenges concerning an oncologically safe tissue removal without overwhelming functional and aesthetic impairment.Materials and methodsIn this randomized controlled trial, a newly introduced intraoral 445-nm semiconductor laser (2W; cw-mode; SIROLaser Blue, Dentsply Sirona, Bensheim, Germany) was used in the therapy of OPMDs. Duration and course of wound healing, pain, and scar tissue formation were compared to classical cold blade removal with primary suture by measuring remaining wound area, tissue colorimetry, and visual analogue scale. The study includes 40 patients randomized using a random spreadsheet sequence in two groups (n1 = 20; n2 = 20).ResultsThis comparative analysis revealed a significantly reduced remaining wound area after 1, 2, and 4 weeks in the laser group compared to the cold blade group (p < 0.05). In the laser group, a significantly reduced postoperative pain after 1 week was measured (p < 0.05).ConclusionLaser coagulation of OPMDs with the investigated 445-nm semiconductor laser is a safe, gentle, and predictable surgical procedure with beneficial wound healing and reduced postoperative discomfort.Clinical relevanceCompared to the more invasive and bloody cold blade removal with scalpel, the 445-nm semiconductor laser could be a new functional less traumatic tool in the therapy of OPMDs. The method should be further investigated with regard to the identification of further possible indications.Trail registrationGerman Clinical Trials Register No: DRKS00032626.

Chiari-like malformation in a cat

Chiari-like malformations are rare in cats. In this case report, the aim is to share data on the diagnosis and treatment of a Chiari-like malformation in a cat. This case report is for an 8 month old, 3 kg, female, mixed breed cat. The cat was brought in by its owner with complaints of seizures and weakness in the hind limb. Clinical and neurological examination revealed signs of ataxic gait, tetraparesis, allodynia and decreased corneal reflexes. As a result of the examinations, a cranial or cervical lesion was suspected. Magnetic resonance imaging revealed findings such as ventriculomegaly, cerebellar herniation, medullary kinging, syringomyelia, and decreased cerebrospinal fluid flow at the first cervical level. Computed tomography revealed the absence of atlantooccipital overlap. In light of the findings, the patient was diagnosed with a Chiari-like malformation. Phenobarbital, gabapentin, furasemide, and prednisone were used for medical treatment. However, despite a week of medical treatment, no improvement was observed. Foramen magnum decompression was preferred as the operation method and titanium mesh was used to prevent scar tissue formation. The patient, whose condition improved in the postoperative period, died one week later due to aspiration pneumonia.

Mitigating Scar Tissue Formation in Tendon Injuries: Targeting HMGB1, AMPK Activation, and Myofibroblast Migration All at Once.

Tendon injuries, while prevalent, present significant challenges regarding their structural and functional restoration. Utilizing alpha-smooth muscle actin (α-SMA)-Ai9-scleraxis (Scx)-green fluorescent protein (GFP) transgenic mice, which exhibit both Scx (a tendon cell marker) and α-SMA (a myofibroblast marker), we explored the effects of metformin (Met) on tendon healing, repair, and its mechanisms of action. Our findings revealed that intraperitoneal (IP) injections of Met, administered before or after injury, as well as both, effectively prevented the release of HMGB1 into the tendon matrix and reduced circulating levels of HMGB1. Additionally, Met treatment increased and activated AMPK and suppressed TGF-β1 levels within the healing tendon. Tendon healing was also improved by blocking the migration of α-SMA+ myofibroblasts, reducing the prevalence of disorganized collagen fibers and collagen type III. It also enhanced the presence of collagen type I. These outcomes highlight Met's anti-fibrotic properties in acutely injured tendons and suggest its potential for repurposing as a therapeutic agent to minimize scar tissue formation in tendon injuries, which could have profound implications in clinical practice.

Management of hemi-mandibulectomy patient with prosthetic devices

The success in rehabilitating a patient with hemi-mandibulectomy depends upon the nature and extent of the surgical defect, treatment plan, type of prosthesis, and patient co-operation. The management becomes more challenging when the prosthetic reconstruction has been delayed. The scar tissue forms and the soft tissue becomes stiff, causing severe deviation in the mandible towards the resected side. This case report presents a58year old male patient who underwent a mandibular resection surgery after he was diagnosed with buccal mucosa carcinoma. The patient had mandibular deviation and deranged occlusion making his speech, mastication and esthetics compromised.: The patient was provided with a cast guide flange prosthesis in the beginning as a training device to prevent the scar contracture and increase the mandibular movement towards healthy side to increase the intercuspation. After few months of training, when the deviation was reduced, flexible maxillary and mandibular partial dentures were fabricated with double occlusion in the maxillary denture to increase the masticatory efficiency of the patient.This case report attempts to formulate a treatment plan whereby the patient's discomfort could be minimized. The treatment starts with the fabrication of a removable guide flange as a physical therapy device to reduce the mandibular deviation followed by provision of a maxillary denture with double occlusion to obtain maximum intercuspation.The mandibulectomy patient is difficult to manage because a prosthodontist is limited in his ability to provide a reasonable and practical prosthesis. However, if the patients recognize the limitations of their rehabilitation, they would be more appreciative of the prosthodontic therapy that enhances their rehabilitative progress.

Current strategies for regenerative therapy of spinal cord injury

Spinal cord injury (SCI) is a leading cause of death and severe disability amongst young people. The incidence of SCI is 0.6–1.0 per 10,000 individuals. Unfortunately, there are no effective methods of restoring locomotor function for individuals with severe SCI. To address this issue, exoskeleton technology controlled using BCI is actively being developed for prosthetic locomotion. Despite the lack of encouraging data for severe spinal cord injuries, regenerative technologies continue to hold promise for spinal cord repair. The limited options for regenerating the central nervous system in humans necessitate creating new sources of neural stem cells for regeneration. Reprogramming autologous somatic cells neurologically can effectively serve as such a source [1]. Nevertheless, the constitution of neuroglial progenitors, which are necessary for regenerating damaged axons of the pyramidal tract, still requires clarification [2]. Some interesting efforts are underway to directly reprogram glial cells in situ using a variety of biotechnological approaches [3]. Overcoming or preventing the formation of a harsh scar tissue at the injury site is the key obstacle to successful regeneration therapy for SCI. Various scaffolds are being developed to facilitate axon regeneration, and several gene therapy agents are being tested to either knock down scar formation factors or activate extracellular matrix remodeling and reparative regeneration. Neuromodulation shows promise for SCI treatment. Studies indicate that epidural stimulation of the L2-S1 spinal cord in humans and mammals activates SPG neurons, aiding spinal walking generator functions. A potentially successful treatment approach involves scaffolds with reprogrammed cells and neuromodulation [4].

Identification of Periostin as a critical niche for myofibroblast dynamics and fibrosis during tendon healing

Tendon injuries are a major clinical problem, with poor patient outcomes caused by abundant scar tissue deposition during healing. Myofibroblasts play a critical role in the initial restoration of structural integrity after injury. However, persistent myofibroblast activity drives the transition to fibrotic scar tissue formation. As such, disrupting myofibroblast persistence is a key therapeutic target. While myofibroblasts are typically defined by the presence of αSMA+ stress fibers, αSMA is expressed in other cell types including the vasculature. As such, modulation of myofibroblast dynamics via disruption of αSMA expression is not a translationally tenable approach. Recent work has demonstrated that Periostin-lineage (PostnLin) cells are a precursor for cardiac fibrosis-associated myofibroblasts. In contrast to this, here we show that PostnLin cells contribute to a transient αSMA+ myofibroblast population that is required for functional tendon healing, and that Periostin forms a supportive matrix niche that facilitates myofibroblast differentiation and persistence. Collectively, these data identify the Periostin matrix niche as a critical regulator of myofibroblast fate and persistence that could be targeted for therapeutic manipulation to facilitate regenerative tendon healing.

Research progress of traditional Chinese medicine in improving hepatic fibrosis based on inhibiting pathological angiogenesis.

Hepatic fibrosis is the formation of scar tissue in the liver. This scar tissue replaces healthy liver tissue and can lead to liver dysfunction and failure if left untreated. It is usually caused by chronic liver disease, such as hepatitis B or C, alcohol abuse, or non-alcoholic fatty liver disease. Pathological angiogenesis plays a crucial role in the development of hepatic fibrosis by promoting the growth of new blood vessels in the liver. These new vessels increase blood flow to the damaged areas of the liver, which triggers the activation of hepatic stellate cells (HSCs). HSCs are responsible for producing excess collagen and other extracellular matrix proteins that contribute to the development of fibrosis. Pathological angiogenesis plays a crucial role in the development of hepatic fibrosis by promoting the growth of new blood vessels in the liver. These new vessels increase blood flow to the damaged areas of the liver, which triggers the activation of HSCs. HSCs are responsible for producing excess collagen and other extracellular matrix proteins that contribute to the development of fibrosis. Traditional Chinese medicine (TCM) has been found to target pathological angiogenesis, thereby providing a potential treatment option for hepatic fibrosis. Several studies have demonstrated that TCM exhibits anti-angiogenic effects by inhibiting the production of pro-angiogenic factors, such as vascular endothelial growth factor and angiopoietin-2, and by reducing the proliferation of endothelial cells. Reviewing and highlighting the unique TCM recognition of treating hepatic fibrosis by targeting pathological angiogenesis may shed light on future hepatic fibrosis research.

#277 : Transcriptome Analysis Revealed a Delayed and Attenuated Estrogen Response in IUA Patients

Background and Aims: Intrauterine adhesion (IUA) is characterized by the formation of scar tissue in the endometrium following a variety of insults such as endometrial damage, miscarriage, and infection. Despite current management with intrauterine adhesion separation and adjuvant therapies such as estrogen supplementation, a high recurrence rate and inadequate therapeutic response persist in some patients. More importantly, compromised endometrial proliferation in these patients lead to subsequent infertility. However, effective therapies to improve the impaired response to estrogen have yet to be identified. This study seeks to elucidate the molecular basis for the adverse estrogen response in IUA patients and to identify novel therapeutic targets. Method: Whole-Transcriptome sequencing: proliferative endometrium of normal and IUA patients. Results: By performing differential and enrichment analysis of transcriptomic data, we observed a considerable downregulation of estrogen-relatedgenesets in IUA patients. The expression of enhancer RNAs (eRNAs) serves as a hallmark of transcriptional activation. By identifying eRNAs in transcriptomic data and co-analyzing with ERa ChIPseq and H3K27ac ChIPseq datasets, we identified a series of downregulated eRNAs, which is mediated by estrogen. We further confirmed the downregulation of eRNAs and target genes. Interestingly, the expression of ESR1 is similar in both groups, we performed immunofluorescence analysis and demonstrated a considerable reduction of ERa-positive cells with a loss of nuclear localization in IUA. This finding provides further evidence of the insensitivity of IUA patients to estrogen and suggests a loss of estrogen genomic effects. Furthermore, we found that prolonging estrogen exposure time and increasing estrogen concentration partially enhanced estrogen effects in IUA patients, yet remained compromised, indicating the need for alternative therapeutic strategies. Conclusion: The compromised response to estrogen in IUA patients is attributed to the attenuation of estrogen receptor alpha (ERa)-mediated genomic effect.

Arthrofibrosis After Total Knee Arthroplasty

» Arthrofibrosis after total knee arthroplasty (TKA) is the new formation of excessive scar tissue that results in limited ROM, pain, and functional deficits.» The diagnosis of arthrofibrosis is based on the patient's history, clinical examination, absence of alternative diagnoses from diagnostic testing, and operative findings. Imaging is helpful in ruling out specific causes of stiffness after TKA. A biopsy is not indicated, and no biomarkers of arthrofibrosis exist.» Arthrofibrosis pathophysiology is multifactorial and related to aberrant activation and proliferation of myofibroblasts that primarily deposit type I collagen in response to a proinflammatory environment. Transforming growth factor-beta signaling is the best established pathway involved in arthrofibrosis after TKA.» Management includes both nonoperative and operative modalities. Physical therapy is most used while revision arthroplasty is typically reserved as a last resort. Additional investigation into specific pathophysiologic mechanisms can better inform targeted therapeutics.

Materials and Device Designs for Wireless Monitoring of Temperature and Thermal Transport Properties of Wound Beds during Healing.

Chronic wounds represent a major health risk for diabetic patients. Regeneration of such wounds requires regular medical treatments over periods that can extend for several months or more. Schemes for monitoring the healing process can provide important feedback to the patient and caregiver. Although qualitative indicators such as malodor or fever can provide some indirect information, quantitative measurements of the wound bed have the potential to yield important insights. The work presented here introduces materials and engineering designs for a wireless system that captures spatio-temporal temperature and thermal transport information across the wound continuously throughout the healing process. Systematic experimental and computational studies establish the materials aspects and basic capabilities of this technology. In vivo studies reveal that both the temperature and the changes in this quantity offer information on wound status, with indications of initial exothermic reactions and mechanisms of scar tissue formation. Bioresorbable materials serve as the foundations for versions of this device that create possibilities for monitoring on and within the wound site, in a way that bypasses the risks of physical removal.

A New Bioactive Fibrin Formulation Provided Superior Cartilage Regeneration in a Caprine Model

The effective and long-term treatment of cartilage defects is an unmet need among patients worldwide. In the past, several synthetic and natural biomaterials have been designed to support functional articular cartilage formation. However, they have mostly failed to enhance the terminal stage of chondrogenic differentiation, leading to scar tissue formation after the operation. Growth factors substantially regulate cartilage regeneration by acting on receptors to trigger intracellular signaling and cell recruitment for tissue regeneration. In this study, we investigated the effect of recombinant insulin-like growth factor 1 (rIGF-1), loaded in fibrin microbeads (FibIGF1), on cartilage regeneration. rIGF-1-loaded fibrin microbeads were injected into full-thickness cartilage defects in the knees of goats. The stability, integration, and quality of tissue repair were evaluated at 1 and 6 months by gross morphology, histology, and collagen type II staining. The in vivo results showed that compared to plain fibrin samples, particularly at 6 months, FibIGF1 improved the functional cartilage formation, confirmed through gross morphology, histology, and collagen type II immunostaining. FibIGF1 could be a promising candidate for cartilage repair in the clinic.

Analisis Dinamik Model SIRC pada Transmisi Hepatitis B dengan Sirosis Hati

Hepatitis B is an infection of the liver that can cause liver cirrhosis. Liver cirrhosis can occur due to the formation of scar tissue in individuals who have prolonged hepatitis B. Transmission of hepatitis B can occur in two ways, namely horizontal and vertical. In this research, this problem is modeled in a mathematical model using the SIRC model, where the population is grouped into four sub-populations, namely susceptible (S), infected (I), cured or immune due to vaccination (R) and cirrhosis. liver (C). From the analysis, two equilibrium points were obtained, namely the disease-free equilibrium point the endemic equilibrium point The basic reproduction number is obtained using the Next Generation Matrix. The analysis results show that if , then the disease-free equilibrium point is locally asymptotically stable, which means that hepatitis B transmission in liver cirrhosis does not spread. Meanwhile, if , then the disease-free equilibrium point is locally asymptotically stable, which means that hepatitis B transmission in liver cirrhosis does not spread. Meanwhile, if , this means that hepatitis B transmission in liver cirrhosis is influenced by contact between susceptible and infectious individuals. To support the results of the analytical analysis, numerical simulations are provided to describe the behavior of the SIRC model.

An Exosome-Rich Conditioned Medium from Human Amniotic Membrane Stem Cells Facilitates Wound Healing via Increased Reepithelization, Collagen Synthesis, and Angiogenesis.

Tissue regeneration is an essential requirement for wound healing and recovery of organs' function. It has been demonstrated that wound healing can be facilitated by activating paracrine signaling mediated by exosomes secreted from stem cells, since exosomes deliver many functional molecules including growth factors (GFs) and neurotrophic factors (NFs) effective for tissue regeneration. In this study, an exosome-rich conditioned medium (ERCM) was collected from human amniotic membrane stem cells (AMSCs) by cultivating the cells under a low oxygen tension (2% O2 and 5% CO2). The contents of GFs and NFs including keratinocyte growth factor, epidermal growth factor, fibroblast growth factor 1, transforming growth factor-β, and vascular endothelial growth factor responsible for skin regeneration were much higher (10-30 folds) in the ERCM than in normal conditioned medium (NCM). In was found that CM-DiI-labeled exosomes readily entered keratinocytes and fibroblasts, and that ERCM not only facilitated the proliferation of keratinocytes in normal condition, but also protected against H2O2 cytotoxicity. In cell-migration assay, the scratch wound in keratinocyte culture dish was rapidly closed by treatment with ERCM. Such wound-healing effects of ERCM were confirmed in a rat whole skin-excision model: i.e., the wound closure was significantly accelerated, remaining minimal crusts, by topical application of ERCM solution (4 × 109 exosome particles/100 μL) at 4-day intervals. In the wounded skin, the deposition of collagens was enhanced by treatment with ERCM, which was supported by the increased production of collagen-1 and collagen-3. In addition, enhanced angiogenesis in ERCM-treated wounds was confirmed by increased von Willebrand factor (vWF)-positive endothelial cells. The results indicate that ERCM from AMSCs with high concentrations of GFs and NFs improves wound healing through tissue regeneration not only by facilitating keratinocyte proliferation for skin repair, but also activating fibroblasts for extracellular matrix production, in addition to the regulation of angiogenesis and scar tissue formation.

The Material World of 3D-Bioprinted and Microfluidic-Chip Models of Human Liver Fibrosis.

Biomaterials are extensively used to mimic cell-matrix interactions, which are essential for cell growth, function, and differentiation. This is particularly relevant when developing in vitro disease models of organs rich in extracellular matrix, like the liver. Liver disease involves a chronic wound-healing response with formation of scar tissue known as fibrosis. At early stages, liver disease can be reverted, but as disease progresses, reversion is no longer possible, and there is no cure. Research for new therapies is hampered by the lack of adequate models that replicate the mechanical properties and biochemical stimuli present in the fibrotic liver. Fibrosis is associated with changes in the composition of the extracellular matrix that directly influence cell behavior. Biomaterials could play an essential role in better emulating the disease microenvironment. In this paper, the recent and cutting-edge biomaterials used for creating in vitro models of human liver fibrosis are revised, in combination with cells, bioprinting, and/or microfluidics. These technologies have been instrumental to replicate the intricate structure of the unhealthy tissue and promote medium perfusion that improves cell growth and function, respectively. A comprehensive analysis of the impact of material hints and cell-material interactions in a tridimensional context is provided.

Ag nanocomposite hydrogels with immune and regenerative microenvironment regulation promote scarless healing of infected wounds

BackgroundBacterial infection, complex wound microenvironment and persistent inflammation cause delayed wound healing and scar formation, thereby disrupting the normal function and appearance of skin tissue, which is one of the most problematic clinical issues. Although Ag NPs have a strong antibacterial effect, they tend to oxidize and form aggregates in aqueous solution, which reduces their antibacterial efficacy and increases their toxicity to tissues and organs. Current research on scar treatment is limited and mainly relies on growth factors and drugs to reduce inflammation and scar tissue formation. Therefore, there is a need to develop methods that effectively combine drug delivery, antimicrobial and anti-inflammatory agents to modulate the wound microenvironment, promote wound healing, and prevent skin scarring.ResultsHerein, we developed an innovative Ag nanocomposite hydrogel (Ag NCH) by incorporating Ag nanoparticles (Ag NPs) into a matrix formed by linking catechol-modified hyaluronic acid (HA-CA) with 4-arm PEG-SH. The Ag NPs serve dual functions: they act as reservoirs for releasing Ag/Ag+ at the wound site to combat bacterial infections, and they also function as cross-linkers to ensure the sustained release of basic fibroblast growth factor (bFGF). The potent antibacterial effect of the Ag NPs embedded in the hydrogel against S.aureus was validated through comprehensive in vitro and in vivo analyses. The microstructural analysis of the hydrogels and the in vitro release studies confirmed that the Ag NCH possesses smaller pore sizes and facilitates a slower, more sustained release of bFGF. When applied to acute and infected wound sites, the Ag NCH demonstrated remarkable capabilities in reshaping the immune and regenerative microenvironment. It induced a shift from M1 to M2 macrophage polarization, down-regulated the expression of pro-inflammatory factors such as IL-6 and TNF-α, and up-regulated the expression of anti-inflammatory IL-10. Furthermore, the Ag NCH played a crucial role in regulating collagen deposition and alignment, promoting the formation of mature blood vessels, and significantly enhancing tissue reconstruction and scarless wound healing processes.ConclusionsWe think the designed Ag NCH can provide a promising therapeutic strategy for clinical applications in scarless wound healing and antibacterial therapy.Graphical

Biomimetic nanoplatform with anti-inflammation and neuroprotective effects for repairing spinal cord injury in mice

Regeneration in the therapeutics of spinal cord injury (SCI) remains a challenge caused by the hyperinflammation microenvironment. Nanomaterials-based treatment strategies for diseases with excellent therapeutic efficacy are actively pursued. Here, we develop biodegradable poly (lactic-co-glycolic acid) nanoparticles (PLGA) obtained by loading celastrol (pCel) for SCI thrapy. Cel, as an antioxidant drug, facilitated reactive oxygen species (ROS) scavenging, and decreased the generation of pro-inflammatory cytokines. To facilitate its administration, pCel is formulated into microspheres by oil-in-water (O/W) emulsion/solvent evaporation technique. The constructed pCel can induced polarization of macrophages and obviously improved lipopolysaccharide (LPS) and interferon-γ (IFN-γ)-induced mitochondrial dysfunction, and increased neurite length in PC12 cells and primary neurons. In vivo experiments revealed that pCel regulated the phenotypic polarization of macrophages, prevented the release of pro-inflammatory cytokines, promoted myelin regeneration and inhibited scar tissue formation, and further improve motor function. These findings indicated that the neuroprotective effect of this artificial biodegradable nanoplatform is benefit for the therapy of SCI. This research opens an exciting perspective for the application of SCI treatment and supports the clinical significance of pCel.

Near complete quadriceps tendon healing 2 years following harvest in anterior cruciate ligament reconstruction.

Despite the recent increase in the use of quadriceps tendon (QT) autograft in anterior cruciate ligament reconstruction (ACLR); however, there remains a paucity of literature evaluating the postoperative morphology of the QT. The present study aimed to determine the postoperative morphologic change of the QT at a minimum of 2years following harvesting during ACLR. Patients who underwent ACLR with QT autograft and underwent magnetic resonance imaging (MRI) at a minimum of 2years following harvesting were retrospectively included in the study. The anterior-to-posterior (A-P) thickness, medial-to-lateral (M-L) width, cross-sectional area (CSA), and signal/noise quotient (SNQ) of the QT were assessed at 5mm, 15mm, and 30mm proximal to the superior pole of the patella on MRI. The CSA was adjusted by the angle between the QT and the plane of the axial cut based on a cosine function (adjusted CSA). The A-P thickness, M-L width, adjusted CSA, and SNQ were compared pre- and postoperatively. In addition, defects or scar tissue formation in the harvest site were investigated on postoperative MRI. Thirty patients were recruited for the study. The mean duration between postoperative MRI and surgery was 2.8 ± 1.1years. The mean A-P thickness was 10.3% and 11.9% larger postoperatively at 5mm and 15mm, respectively. The mean M-L width was 7.3% and 6.5% smaller postoperatively at 5mm and 15mm, respectively. There were no significant differences in the adjusted CSA between pre- and post-operative states (275.7 ± 71.6 mm2 vs. 286.7 ± 91.8 mm2, n.s.). There was no significant difference in the postoperative change in the SNQ of the QT at all assessment locations. Defect or scar tissue formation at the harvest site was observed in 4 cases (13.3%), and 5 cases (16.6%), respectively. At a minimum of 2years following QT harvest during ACLR, the QT became slightly thicker and narrower (approximately 11% and 7%, respectively). While the current study demonstrates that QT re-harvesting can be considered due to nearly normalized tendon morphology, future histological and biomechanical studies are required to determine the re-harvesting potential of the QT. IV.