Regenerative Treatment Options Research Articles

Overview of Available Treatments and Their Limitations for Hypertrophic Facet Joints—A Systematic Review of the Literature

Background: Physicians worldwide face the challenging task of improving patient satisfaction by reducing pain in injured patients. Currently, available therapeutic approaches provide only short-term relief of symptoms without addressing long-term satisfaction. This has led to exploring regenerative treatment options that can deliver better outcomes. One such promising option is platelet-rich plasma (PRP) injections, which are gaining popularity as an alternative to standard steroid injections. Objectives: This study examines the therapeutic effects of PRP injections in adult patients with stress or traumatic injuries. Methods: The systematic literature review yielded 60,301 articles, books, and websites verified and removed from the final project. The final studies used in the report comprised randomized trials, observational studies, and case reports on injecting biologics into the epidural space, facet joints, or sacroiliac joints. In total, 15 reviews and 13 studies were included in this review. Results: In the Wu et al study, 46 participants were randomly divided into group A (0.5 mL PRP injection) and group B (1.5 mL methylprednisolone injection). Although group B initially showed a notable pain reduction at one week, it diminished over 6 months, with group A consistently improving, reaching an 80.96% success rate and higher patient satisfaction. In the study by Singla et al comparing PRP (group P) and corticosteroid (group S) in 40 participants, PRP demonstrated a markedly greater reduction in VAS Scale at 6 weeks and 3 months, with a 90% effectiveness compared with 75% for steroids. Conclusion: PRP injections offer greater pain alleviation, disability reduction, and overall patient satisfaction improvements due to their effect on the immune response to promote the growth and proliferation of damaged tissue. It has also been shown to offer a safer alternative that carries fewer risks than that of transforaminal steroid injections due to promising clinical trials and scientific investigation outcomes. Several of the steroid injection studies proved to have mixed results and efficacy because patients reporting having similar pain relief with placebo groups that used saline injections. Further studies will be needed to evaluate PRP's long-term efficacy and cost-effectiveness for practical patient use in the future.

Surgical and regenerative treatment options for empty nose syndrome: A systematic review.

Patients with empty nose syndrome usually suffer from paradoxical nasal congestion, nasal dryness, epistaxis and suffocation. Conservative management is general option for the empty nose syndrome. However, there are several patients who continually complain of symptoms. If symptoms persist, surgical options are considered. Therefore, we reviewed surgical and regenerative treatment options of empty nose syndrome. PubMed, Embase, Scopus, Cochrane Register of Controlled Trials, and Google Scholar were searched from the earliest date provided in the database until December 2022. In the studies, treatment outcomes were measured by patient symptom scores such as Sino-Nasal Outcome Test (SNOT-20, 22, and 25), and Empty Nose Syndrome 6-Item Questionnaire (ENS6Q) along with various clinical examiniations. Twenty-eight studies were analyzed. Submucosal injectable materials, allografts/xenografts/cadaveric implants, autologous implants, and synthetic implants were used. Among them, polyethylene implant was most commonly used (23.3%), followed by autologous, homologous, or cadaveric costal cartilage (20%). The most common administration site was the anterior-inferior lateral nasal wall. Most of the studies showed that surgical intervention brought significant improvements in clinical findings including endoscopic exam, acoustic rhinometry, and CT, as well as patients reporting nasal symptom-, psychological-, or overall health-related quality of life questionnaires. However, several studies did not confirm improvement effects in some psychological-related questionnaires or saccharin transit time. The average follow-up duration was 12.0 (2.0-27.6) months. Postoperative adverse effects were reported in only two studies. Several surgical options and recent tissue regeneration techniques have shown its positive efficacy in treating empty nose syndrome. However more detailed investigations with a larger number and a randomized control study are needed to establish a standardized protocol in treating empty nose syndrome patients.

EXPLORING THE POTENTIAL OF EXTRACELLULAR VESICLES AS CELL-FREE THERAPEUTICS FOR OSTEOARTHRITIS: IN VIVO AND EX VIVO COMPARATIVE STUDIES

Osteoarthritis (OA) is a degenerative disease that lacks regenerative treatment options. Current research focuses on mesenchymal stem cells (MSCs) and Platelet-Rich Plasma (PRP) as regenerative therapies, but extracellular vesicles (EVs) have shown to be more advantageous. This study compares the regenerative potential of human umbilical cord MSC-derived EVs (cEVs) and platelet-derived EVs (pEVs) in ex vivo and in vivo OA models.In the ex vivo study, OA conditions were induced in human cartilage explants, which were then treated either with pEVs or cEVs. Results showed a higher content of DNA and collagen in the pEVs group compared to control and cEVs groups, suggesting that pEVs could be a potential alternative to cEVs.In the in vivo study, an OA model was established in the knee joints of rats through MIA (monoiodoacetate) injection and then treated either with pEVs or cEVs. Results showed that pEVs-treated knee joints had better subchondral bone integrity and greater OA reversion, particularly in female rats, indicating that pEVs are a viable regeneration treatment for OA and outperform cEVs in terms of efficacy.Overall, the study demonstrates the potential of EVs as a regenerative treatment for OA, with pEVs showing promising results in both ex vivo and in vivo models. The use of pEVs in clinical practice could provide a faster path to translation due to the established use of platelet concentrates in therapeutics. However, further studies are needed to fully evaluate the potential of pEVs for OA treatment and to elucidate the mechanisms behind their regenerative effects.Acknowledgments: The authors thank Dr Fernando Hierro (UIB) for their technical contribution with TEM, Mª Trinidad García (UIB) for the access to radioactivity facilities, Aina Arbós (IUNICS) for her contribution in the histology staining, María Tortosa (IdISBa) for her assistance with the animal care and ADEMA School of Dentistry for the access to the cone beam computed tomography (CBCT).Funding: This research was funded by Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, co-funded by the ESF European Social Fund and the ERDF European Regional Development Fund (MS16/00124; CP16/00124), PROGRAMA JUNIOR del proyecto TALENT PLUS, construyendo SALUD, generando VALOR (JUNIOR01/18), financed by the sustainable tourism tax of the Balearic Islands; the Direcció General d'Investigació and Conselleria d'Investigació, Govern Balear (FPI/2046/2017); the Mecanisme de Recuperació i Resiliència, intended to execute research projects of «Noves polítiques públiques per a un mercat de treball dinàmic, resilient i inclusiu», collected in Pla de Recuperació, Transformació i Resiliència, financed by European Union-Next Generation EU and driven by SOIB and Conselleria de Fons Europeus, Universitat i Cultura i la Conselleria de Model Econòmic, Turisme i Treball (NG0421) and the grant SYN20/03 from IdISBa.

Mesenchymal stem cells: Therapeutic option in ARDS, COPD, and COVID-19 patients

Acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD) and COVID-19 have as a common characteristic the inflammatory lesion of the lung epithelium. The therapeutic options are associated with opportunistic infections, a hyperglycemic state, and adrenal involvement. Therefore, the search for new treatment strategies that reduce inflammation, and promote re-epithelialization of damaged tissue is very important. This work describes the relevant pathophysiological characteristics of these diseases and evaluates recent findings on the immunomodulatory, anti-inflammatory and regenerative effect of mesenchymal stem cells (MSC) and their therapeutic use. In Pubmed we selected the most relevant studies on the subject, published between 2003 and 2022 following the PRISMA guide. We conclude that MSCs are an important therapeutic option for regenerative treatment in COPD, ARDS, and COVID-19, because of their ability to differentiate into type II pneumocytes and maintain the size and function of lung tissue by replacing dead or damaged cells.

Ischemic stroke-related gene expression profiles across species: a meta-analysis

Stroke patients are often left with permanent disabilities with no regenerative treatment options. Unbiased RNA sequencing studies decoding the transcriptional signature of stroked tissue hold promise to identify new potential targets and pathways directed to improve treatment for stroke patients. Here, gene expression profiles of stroked tissue across different time points, species, and stroke models were compared using NCBI GEO database. In total, 34 datasets from mice, rats, humans, and primates were included, exploring gene expression differences in healthy and stroked brain tissue. Distinct changes in gene expression and pathway enrichment revealed the heterogenicity of the stroke pathology in stroke-related pathways e.g., inflammatory responses, vascular repair, remodelling and cell proliferation and adhesion but also in diverse general, stroke-unrelated pathways that have to be carefully considered when evaluating new promising therapeutic targets.

Early and late-onset cell migration from peripheral corneal endothelium.

In this study we describe peripheral corneal endothelial cell migration in vitro in the absence and presence of a ROCK-inhibitor. For this study, 21 corneal endothelial graft rims, with attached trabecular meshwork (TM), were prepared from Descemet membrane-endothelial cell sheets by 6.5 mm trepanation. For the initial proof-of-concept, 7 outer graft rims were cultured in a thermo-reversible hydrogel matrix for up to 47 days. To assess the effect of a ROCK-inhibitor, 14 paired outer rims were cultured either with or without ROCK-inhibitor for up to 46 days. At the end of culture, tissue was retrieved from the hydrogel matrix and examined for cell viability and expression of different endothelial cell markers (ZO-1, Na+/K+-ATPase, NCAM, glypican, and vimentin). All cultured rims remained viable and displayed either single regions (n = 5/21) or collective areas (n = 16/21) of cell migration, regardless of the presence or absence of ROCK-inhibition. Migration started after 4±2 days and continued for at least 29 days. The presence of ROCK-inhibitor seemed to contribute to a more regular cell morphology of migrating cells. In addition, 7 outer rims demonstrated a phenotypically distinct late-onset but fast-growing cell population emerging from the area close to the limbus. These cells emerged after 3 weeks of culture and appeared less differentiated compared to other areas of migration. Immunostaining showed that migrated cells maintained the expression patterns of endothelial cell markers. In conclusion, we observed 2 morphologically distinct migrating cell populations with the first type being triggered by a broken physical barrier, which disrupted contact inhibition and the second, late-onset type showing a higher proliferative capacity though appearing less differentiated. This cell subpopulation appeared to be mediated by stimuli other than loss of contact inhibition and ROCK-inhibitor presence. Further exploration of the differences between these cell types may assist in optimizing regenerative treatment options for endothelial diseases.

A Gout Flare Caused by the Administration of Platelet Rich Plasma: A Clinical Case

The therapy with Platelet Rich Plasma (PRP) administered in degenerated or injured musculoskeletal tissues is a new and promising regenerative treatment option. Traditionally, it is considered that as PRP represents an autologous (to the patient) blood product, the potential for serious side effects is neglectable. Consequently, it is important that any significant negative consequences are well described. We present a fifty-five years old male patient, complaining of pain and stiffness in his right ankle joint due to multiple traumas during his earlier sport career. He had no any contraindications and PRP was injected intraarticularly under ultrasound guidance. On the next day, the patient developed an intensive pain and swelling in the regions of the right ankle and the dorsum of the right foot. The acute phase reactants were elevated and there was no leukocytosis. On ultrasound examination, there was an effusion in the tibiotalar and talonavicular joints. Arthrocentesis was performed and the microscopic examination revealed the typical needle shaped monosodium urate crystals inside the joint fluid and no bacteria. Consequently, the diagnosis of acute gouty flare was made (the patient has a history of gout, but did not have any flares in the past two years). As PRP concentrate contains naturally many proinflammatory molecules, we speculate that some of them may activate the macrophages that residue normally in the synovium and the capsule of the injected joint. The activated macrophages further may react to the MSU crystals deposited there, leading to the development of a gouty flare. In conclusion, the possibility of a flare should be explained to gouty patients, candidate for PRP treatment.

Prevention of Oxidative Damage in Spinal Cord Ischemia Upon Aortic Surgery: First-In-Human Results of Shock Wave Therapy Prove Safety and Feasibility.

Background Spinal cord ischemia (SCI) remains a devastating complication after aortic dissection or repair. A primary hypoxic damage is followed by a secondary damage resulting in further cellular loss via apoptosis. Affected patients have a poor prognosis and limited therapeutic options. Shock wave therapy (SWT) improves functional outcome, neuronal degeneration and survival in murine spinal cord injury. In this first-in-human study we treated 5 patients with spinal cord ischemia with SWT aiming to prove safety and feasibility. Methods and Results Human neurons were subjected to ischemic injury with subsequent SWT. Reactive oxygen species and cellular apoptosis were quantified using flow cytometry. Signaling of the antioxidative transcription factor NRF2 (nuclear factor erythroid 2-related factor 2) and immune receptor Toll-like receptor 3 (TLR3) were analyzed. To assess whether SWT act via a conserved mechanism, transgenic tlr3-/- zebrafish created via CRISPR/Cas9 were subjected to spinal cord injury. To translate our findings into a clinical setting, 5 patients with SCI underwent SWT. Baseline analysis and follow-up (6 months) included assessment of American Spinal Cord Injury Association (ASIA) impairment scale, evaluation of Spinal Cord Independence Measure score and World Health Organization Quality of Life questionnaire. SWT reduced the number of reactive oxygen species positive cells and apoptosis upon ischemia via induction of the antioxidative factor nuclear factor erythroid 2-related factor 2. Inhibition or deletion of tlr3 impaired axonal growth after spinal cord lesion in zebrafish, whereas tlr3 stimulation enhanced spinal regeneration. In a first-in-human study, we treated 5 patients with SCI using SWT (mean age, 65.3 years). Four patients presented with acute aortic dissection (80%), 2 of them exhibited preoperative neurological symptoms (40%). Impairment was ASIA A in 1 patient (20%), ASIA B in 3 patients (60%), and ASIA D in 1 patient (20%) at baseline. At follow-up, 2 patients were graded as ASIA A (40%) and 3 patients as ASIA B (60%). Spinal cord independence measure score showed significant improvement. Examination of World Health Organization Quality of Life questionnaires revealed increased scores at follow-up. Conclusions SWT reduces oxidative damage upon SCI via immune receptor TLR3. The first-in-human application proved safety and feasibility in patients with SCI. SWT could therefore become a powerful regenerative treatment option for this devastating injury.

Novel In Situ-Cross-Linked Electrospun Gelatin/Hydroxyapatite Nonwoven Scaffolds Prove Suitable for Periodontal Tissue Engineering.

Periodontal diseases affect millions of people worldwide and can result in tooth loss. Regenerative treatment options for clinical use are thus needed. We aimed at developing new nonwoven-based scaffolds for periodontal tissue engineering. Nonwovens of 16% gelatin/5% hydroxyapatite were produced by electrospinning and in situ glyoxal cross-linking. In a subset of scaffolds, additional porosity was incorporated via extractable polyethylene glycol fibers. Cell colonization and penetration by human mesenchymal stem cells (hMSCs), periodontal ligament fibroblasts (PDLFs), or cocultures of both were visualized by scanning electron microscopy and 4′,6-diamidin-2-phenylindole (DAPI) staining. Metabolic activity was assessed via Alamar Blue® staining. Cell type and differentiation were analyzed by immunocytochemical staining of Oct4, osteopontin, and periostin. The electrospun nonwovens were efficiently populated by both hMSCs and PDLFs, while scaffolds with additional porosity harbored significantly more cells. The metabolic activity was higher for cocultures of hMSCs and PDLFs, or for PDLF-seeded scaffolds. Periostin and osteopontin expression was more pronounced in cocultures of hMSCs and PDLFs, whereas Oct4 staining was limited to hMSCs. These novel in situ-cross-linked electrospun nonwoven scaffolds allow for efficient adhesion and survival of hMSCs and PDLFs. Coordinated expression of differentiation markers was observed, which rendered this platform an interesting candidate for periodontal tissue engineering.

Articular Cartilage Regeneration in Veterinary Medicine.

Cartilage is an avascular tissue with a limited rate of oxygen and nutrient diffusion, resulting in its inability to heal spontaneously. Articular cartilage defects eventually lead to osteoarthritis (OA), the endpoint of progressive destruction of cartilage. In companion animals, OA is the most common joint disease, and many pain management and surgical attempts have been made to find an appropriate treatment. Pain management of OA is usually the first choice of OA therapy, which is often managed with nonsteroidal anti-inflammatory drugs (NSAIDs). To avoid known negative side effects of NSAIDs, other approaches are being considered, such as the use of anti-nerve growth factor monoclonal antibodies (anti-NGF mAB), hyaluronic acid (HA), platelet-rich plasma (PRP), and mesenchymal stem cells (MSCs). The latter is increasingly being recognized as effective in reducing or even eliminating pain and lameness associated with OA. However, the in vivo mechanisms of MSC action do not relate to their differentiation potential, but rather to their immunomodulatory functions. Achieving actual regeneration of cartilage to prevent OA from developing or even revert already existing OA condition has not yet been achieved. Several techniques have been tried to overcome cartilage's inability to regenerate, from osteochondral transplantation, autologous chondrocyte implantation (ACI), and matrix-induced ACI (MACI). Combinatory use of MSCs unique features and biomaterials is also being investigated with the aim to as much as possible recapitulate the native microenvironment of the cartilage, yet so far none of the methods have produced reliable and truly effective results. Although OA, for now, remains an incurable disease, novel techniques are being developed, rendering hope for the future accomplishment of actual cartilage regeneration. The aim of this chapter is firstly to summarize known and developing pain management options for OA, secondly to present surgical attempts to regenerate articular cartilage, and finally to present the attempts to improve existing regenerative treatment options using mesenchymal stem cells, with the vision for the possible use of developing strategies in veterinary medicine.

Regenerative Medicine of Liver: Promises, Advances and Challenges

Liver tissue engineering is a rapidly developing field which combines the novel use of liver cells, appropriate biochemical factors, and engineering principles, in order to replace or regenerate damaged liver tissue or the organ. The aim of this review paper is to critically investigate different possible methods to tackle issues related with liver diseases/disorders mainly using regenerative medicine. In this work the various regenerative treatment options are discussed, for improving the prognosis of chronic liver disorders. By reviewing existing literature, it is apparent that the current popular treatment option is liver transplantation, although the breakthroughs of stem cell-based therapy and bioartificial liver technology make them a promising alternative.

A contemporary review of therapeutic and regenerative management of intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) remains a common and debilitating form of stroke. This neurological emergency must be diagnosed and treated rapidly yet effectively. In this article, we review the medical, surgical, repair, and regenerative treatment options for managing ICH. Topics of focus include the management of blood pressure, intracranial pressure, coagulopathy, and intraventricular hemorrhage, as well as the role of surgery, regeneration, rehabilitation, and secondary prevention. Results of various phase II and III trials are incorporated. In summary, ICH patients should undergo rapid evaluation with neuroimaging, and early interventions should include systolic blood pressure control in the range of 140 mmHg, correction of coagulopathy if indicated, and assessment for surgical intervention. ICH patients should be managed in dedicated neurosurgical intensive care or stroke units where continuous monitoring of neurological status and evaluation for neurological deterioration is rapidly possible. Extravasation of hematoma may be helpful in patients with intraventricular extension of ICH. The goal of care is to reduce mortality and enable multimodal rehabilitative therapy.

Hyperbaric oxygen therapy ameliorates the symptoms of post-concussion syndrome by inhibiting MMP-9 activity: a randomized controlled trial in Indonesia

Introduction: Post-concussion syndrome is common in young adults and can greatly interfere with the quality of daily life. It has a wide range of symptoms that require prompt and well-targeted treatment to avoid further brain impairment. Hyperbaric oxygen therapy (HBOT) is a promising regenerative treatment option for these patients to help prevent the progression of post-concussion syndrome. This study aims to determine whether HBOT accelerates the healing process and reduces symptoms in patients with post-concussion syndrome. Methods: 20 patients with post-concussion syndrome participated in this randomized controlled trial study. After receiving standard mild traumatic brain injury treatment in accordance with the Advanced Trauma Life Support guidelines, the patients were divided into HBOT and control groups. Matrix metallopeptidase 9 (MMP-9) levels and Rivermead Post-Concussion Symptoms Questionnaire (RPQ) scores were used to compare the two groups (before HBOT & after 1st, 3rd, and 5th week). Results: The study sample was predominantly male (65%) with an average age of 60 years old. HBOT reduced serum MMP-9 levels by nearly 20 ng/mL (p < 0.001) compared with the control treatment. The efficacy of HBOT was also reflected in the RPQ scores, which were significantly lower in the HBOT group than the control group (before HBOT & after 1st, 3rd, 5th week) (-3.80 on RPQ-3, p = p<0.001; -16.20 on RPQ-13, p = p<0.001). Conclusion: HBOT ameliorated the symptoms associated with post-concussion syndrome through a mechanism that involves MMP-9 activity. The accelerated recovery observed in the present study supports the use of HBOT to treat post-concussion syndrome and potentially other forms of traumatic brain injury.

Multiscale Regulation of the Intervertebral Disc: Achievements in Experimental, In Silico, and Regenerative Research.

Intervertebral disc (IVD) degeneration is a major risk factor of low back pain. It is defined by a progressive loss of the IVD structure and functionality, leading to severe impairments with restricted treatment options due to the highly demanding mechanical exposure of the IVD. Degenerative changes in the IVD usually increase with age but at an accelerated rate in some individuals. To understand the initiation and progression of this disease, it is crucial to identify key top-down and bottom-up regulations’ processes, across the cell, tissue, and organ levels, in health and disease. Owing to unremitting investigation of experimental research, the comprehension of detailed cell signaling pathways and their effect on matrix turnover significantly rose. Likewise, in silico research substantially contributed to a holistic understanding of spatiotemporal effects and complex, multifactorial interactions within the IVD. Together with important achievements in the research of biomaterials, manifold promising approaches for regenerative treatment options were presented over the last years. This review provides an integrative analysis of the current knowledge about (1) the multiscale function and regulation of the IVD in health and disease, (2) the possible regenerative strategies, and (3) the in silico models that shall eventually support the development of advanced therapies.

Defining a therapeutic range for regeneration of ischemic myocardium via shock waves

Shockwave therapy (SWT) represents a promising regenerative treatment option for patients with ischemic cardiomyopathy. Although no side-effects have been described upon SWT, potential cellular damage at therapeutic energies has not been addressed so far. In this work, we aimed to define a therapeutic range for shock wave application for myocardial regeneration. We could demonstrate that SWT does not induce cellular damage beneath energy levels of 0.27 mJ/mm2 total flux density. Endothelial cell proliferation, angiogenic gene expression and phosphorylation of AKT and ERK are enhanced in a dose dependent manner until 0.15 mJ/mm2 energy flux density. SWT induces regeneration of ischemic muscle in vivo via expression of angiogenic gene expression, enhanced neovascularization and improved limb perfusion in a dose-dependent manner. Therefore, we provide evidence for a dose-dependent induction of angiogenesis after SWT, as well as the absence of cellular damage upon SWT within the therapeutic range. These data define for the first time a therapeutic range of SWT, a promising regenerative treatment option for ischemic cardiomyopathy.

Osteochondral scaffolds for early treatment of cartilage defects in osteoarthritic joints: from bench to clinic.

ABSTRACTOsteoarthritis is a degenerative joint disease, typified by the loss in the quality of cartilage and bone at the interface of a synovial joint, resulting in pain, stiffness and reduced mobility. The current surgical treatment for advanced stages of the disease is joint replacement, where the non-surgical therapeutic options or less invasive surgical treatments are no longer effective. These are major surgical procedures which have a substantial impact on patients’ quality of life and lifetime risk of requiring revision surgery. Treatments using regenerative methods such as tissue engineering methods have been established and are promising for the early treatment of cartilage degeneration in osteoarthritis joints. In this approach, 3-dimensional scaffolds (with or without cells) are employed to provide support for tissue growth. However, none of the currently available tissue engineering and regenerative medicine products promotes satisfactory durable regeneration of large cartilage defects. Herein, we discuss the current regenerative treatment options for cartilage and osteochondral (cartilage and underlying subchondral bone) defects in the articulating joints. We further identify the main hurdles in osteochondral scaffold development for achieving satisfactory and durable regeneration of osteochondral tissues. The evolution of the osteochondral scaffolds – from monophasic to multiphasic constructs – is overviewed and the osteochondral scaffolds that have progressed to clinical trials are examined with respect to their clinical performances and their potential impact on the clinical practices. Development of an osteochondral scaffold which bridges the gap between small defect treatment and joint replacement is still a grand challenge. Such scaffold could be used for early treatment of cartilage and osteochondral defects at early stage of osteoarthritis and could either negate or delay the need for joint replacements.

Feasibility, technique and accuracy of ultrasound-guided transurethral injections into the urinary sphincter of female cadavers: proof of concept

BackgroundThe injection of muscle precursor cells (MPC) into the external urinary sphincter muscle (EUS) is a promising therapeutic option for regenerative treatment of stress urinary incontinence (SUI). The objective of the present project was to conduct a pre-clinical trial to investigate the feasibility and accuracy of ultrasound (US) guided, transurethral injections into the EUS of female cadavers.MethodsThis is a prospective, anatomical, interventional and radiological cadaveric laboratory investigation. Two urologists performed transurethral US-guided injections to deliver nano-iron particles into the EUS. The intervention was performed in three unfixed, fresh female cadavers. Each cadaver received MRI before and CT as well as MRI of the pelvis after the injections.ResultsThe precision and accumulation of nano-iron particles in the EUS was compared using a rating scale to evaluate left versus right and anterior versus posterior distribution in axial and sagittal orientation with US, MRI and CT. The accuracy of our US-guided injections into the anterior target region yielded 4 points on the rating scale. Adequate precision and accumulation of particles in the left versus right EUS were also demonstrated (3 vs. 3.33 points, respectively). Signal intensity in MRI revealed a mean ratio of 0.33 before and after injection. CT scans showed no relevant artefacts impairing the assessment.ConclusionUS-guided, transurethral injection into the EUS is feasible and imaging reveals a precise accumulation in the target region. Our method provides an appropriate approach to deliver MPC in the EUS muscle for a regenerative treatment of SUI in the near future.

Treatment of Grade 3 and 4 Osteoarthritis with Intraoperatively Separated Adipose Tissue-Derived Stromal Vascular Fraction: A Comparative Case Series.

Osteoarthritis (OA) is the most common form of arthritis of the joints. The stromal vascular fraction (SVF) is a regenerative cell population that can be isolated from adipose tissue. It is the immunomodulatory properties of the stromal vascular fraction that make it a promising candidate for the regenerative treatment of OA. Patients with grade 3 and 4 osteoarthritis were treated with the stromal vascular fraction with and without platelet-rich plasma (PRP) and followed up on their Knee Injury and Osteoarthritis Outcome Score (KOOS) score for 12 months, with MRI and subjective evaluation of the procedure. Magnetic resonance imaging (MRI) revealed a widening of the joint space, a restructuring of the cartilage, and an alleviation of effusions in the treated joints. In three of the four treatment groups, a substantial improvement of the KOOS scores was documented at the 12-month follow-up time point. According to the subjective evaluation, 67% of the patients were satisfied or very satisfied with the procedure and would recommend it to others. No serious adverse events or unwanted side effects related to the SVF treatment were observed or reported. Prior to an invasive artificial joint replacement, the treatment of arthritic knee joints with the intraarticular injection of autologous adipose tissue-derived SVF should be considered a regenerative treatment option.

Shock waves promote spinal cord repair via TLR3.

Spinal cord injury (SCI) remains a devastating condition with poor prognosis and very limited treatment options. Affected patients are severely restricted in their daily activities. Shock wave therapy (SWT) has shown potent regenerative properties in bone fractures, wounds, and ischemic myocardium via activation of the innate immune receptor TLR3. Here, we report on the efficacy of SWT for regeneration of SCI. SWT improved motor function and decreased lesion size in WT but not Tlr3-/- mice via inhibition of neuronal degeneration and IL6-dependent recruitment and differentiation of neuronal progenitor cells. Both SWT and TLR3 stimulation enhanced neuronal sprouting and improved neuronal survival, even in human spinal cord cultures. We identified tlr3 as crucial enhancer of spinal cord regeneration in zebrafish. Our findings indicate that TLR3 signaling is involved in neuroprotection and spinal cord repair and suggest that TLR3 stimulation via SWT could become a potent regenerative treatment option.

Polyetheresterurethane Based Porous Scaffolds with Tailorable Architectures by Supercritical CO2 Foaming

Porous three-dimensional (3D) scaffolds are promising treatment options in regenerative medicine. Supercritical and dense-phase fluid technologies provide an attractive alternative to solvent-based scaffold fabrication methods. In this work, we report on the fabrication of poly-etheresterurethane (PPDO-PCL) based porous scaffolds with tailorable pore size, porosity, and pore interconnectivity by using supercritical CO2 (scCO2) fluid-foaming. The influence of the processing parameters such as soaking time, soaking temperature and depressurization on porosity, pore size, and interconnectivity of the foams were investigated. The average pore diameter could be varied between 100-800 μm along with a porosity in the range from (19 ± 3 to 61 ± 6)% and interconnectivity of up to 82%. To demonstrate their applicability as scaffold materials, selected foams were sterilized via ethylene oxide sterilization. They showed negligible cytotoxicity in tests according to DIN EN ISO 10993-5 and 10993-12 using L929 cells. The study demonstrated that the pore size, porosity and the interconnectivity of this multi-phase semicrystalline polymer could be tailored by careful control of the processing parameters during the scCO2 foaming process. In this way, PPDO-PCL scaffolds with high porosity and interconnectivity are potential candidate materials for regenerative treatment options.