Complications of degenerative lumbar spondylolisthesis and stenosis surgery in patients over 80 s: comparative study with over 60 s and 70 s. Experience with 678 cases.

PURPOSE: Degenerative spondylolisthesis (DS) is a debilitating condition that carries a high economic burden. As the global population ages, the number of patients over 80 years old demanding spinal fusion is constantly rising. Therefore, neurosurgeons often face the important decision as to whether to perform surgery or not in this age group, commonly perceived at high risk for complications. METHODS: Six hundred seventy-eight elder patients, who underwent posterolateral lumbar fusion for DS (performed in three different centers) from 2012 to 2020, were screened for medical, early and late surgical complications and for the presence of potential preoperative risk factors. Patients were divided in three categories based on their age: (1) 60-69 years, (2) 70-79 years, (3) 80 and over. Multiple logistic regression was used to determine the predictive power of age and of other risk factors (i.e., ASA score; BMI; sex; presence or absence of insulin-dependent and -independent diabetes, use of anticoagulants, use of antiaggregants and osteoporosis) for the development of postoperative complications. RESULTS: In univariate analysis, age was significantly and positively correlated with medical complications. However, when controls for other risk factors were added in the regressions, age never reached significance, with the only noticeable exception of cerebrovascular accidents. ASA score and BMI were the two risk factors that significantly correlated with the higher numbers of complication rates (especially medical). CONCLUSION: Patients of different age but with comparable preoperative risk factors share similar postoperative morbidity rates. When considering octogenarians for lumbar arthrodesis, the importance of biological age overrides that of chronological.

Freeze-Dried Secretome (Lyosecretome) from Mesenchymal Stem/Stromal Cells Promotes the Osteoinductive and Osteoconductive Properties of Titanium Cages.

Titanium is one of the most frequently used materials in bone regeneration due to its good biocompatibility, excellent mechanical properties, and great osteogenic performance. However, osseointegration with host tissue is often not definite, which may cause implant failure at times. The present study investigates the capacity of the mesenchymal stem cell (MSC)-secretome, formulated as a ready-to-use and freeze-dried medicinal product (the Lyosecretome), to promote the osteoinductive and osteoconductive properties of titanium cages. In vitro tests were conducted using adipose tissue-derived MSCs seeded on titanium cages with or without Lyosecretome. After 14 days, in the presence of Lyosecretome, significant cell proliferation improvement was observed. Scanning electron microscopy revealed the cytocompatibility of titanium cages: the seeded MSCs showed a spread morphology and an initial formation of filopodia. After 7 days, in the presence of Lyosecretome, more frequent and complex cellular processes forming bridges across the porous surface of the scaffold were revealed. Also, after 14 and 28 days of culturing in osteogenic medium, the amount of mineralized matrix detected by alizarin red was significantly higher when Lyosecretome was used. Finally, improved osteogenesis with Lyosecretome was confirmed by confocal analysis after 28 and 56 days of treatment, and demonstrating the production by osteoblast-differentiated MSCs of osteocalcin, a specific bone matrix protein.

Endoscopic transorbital surgery for spheno-orbital lesions: how I do it.

BACKGROUND: The endoscopic transorbital approach has been recently proposed for the surgical management of spheno-orbital lesions as an alternative to craniotomy surgeries. METHOD: We analyze the technical nuances and what we have changed as our experience increased after the first operations performed for 12 different spheno-orbital lesions. CONCLUSION: The endoscopic transorbital approach is useful for the treatment of selected spheno-orbital lesions and could represent an interesting option in experienced hands. More studies are needed to fully understand its potentialities and limitations.

Tension pneumocephalus secondary to osteoradionecrosis of the clivus.

We report the case of a 36 year-old man with relapsing undifferentiated nasopharyngeal carcinoma treated with a re-irradiation Cyberknife, who subsequently developed tension pneumocephalus due to a cerebrospinal fluid leakage located at the clivus. The fistula was caused by osteonecrosis of the skull base secondary to the tumor invasion and to the sequelae of the radiotherapy. An endoscopic endonasal technique was used in order to repair the defect, with a peduncolated nasoseptal flap harvested to perform the skull base reconstruction. In this paper, we discuss the importance of identifying this possible complication related to radiotherapy in the management of neoplasm along the skull base; moreover, the role of endoscopy in the diagnosis and treatment of skull base fistulas is also described and commented.

Chordoid glioma: a rare radiologically, histologically, and clinically mystifying lesion.

Chordoid glioma (CG) is a rare central nervous system neoplasm (WHO grade II) of uncertain origin whose typical localization is in the anterior part of the third ventricle. Its clinical, radiological, and histological features may vary and furthermore mimic other kind of benign lesions usually associated with a better outcome. We report a case of a 43-year-old female who underwent gross total removal of a lesion of the third ventricle causing hydrocephalus. The imaging studies and the intraoperative examination led at first to a hypothesis of meningioma. Early surgical and neurological outcomes were good. The patient underwent multiple complications related to hypothalamic dysfunctions and thrombohemorragic issues and eventually died because of systemic infections. Definitive examination was of chordoid glioma of the third ventricle. Reviewing literature, we evaluated possible pitfalls in radiological and histological diagnosis as well as in surgical and medical treatment of CGs. Despite their benign presentation, a high incidence of multiple possible severe complications is reported. Early alertness and combined treatment strategies could improve overall CGs treatment strategies.

Rai is a new regulator of neural progenitor migration and glioblastoma invasion.

The invasive nature of glioblastoma (GBM) is one important reason for treatment failure. GBM stem/progenitor cells retain the migratory ability of normal neural stem/progenitor cells and infiltrate the brain parenchyma. Here, we identify Rai (ShcC/N-Shc), a member of the family of Shc-like adaptor proteins, as a new regulator of migration of normal and cancer stem/progenitor cells. Rai is expressed in neurogenic areas of the brain and its knockdown impairs progenitor migration to the olfactory bulb. Its expression is retained in GBM stem/progenitor cells where it exerts the same promigratory activity. Rai silencing in cancer stem/progenitor cells isolated from different patients causes significant decrease in cell migration and invasion, both in vitro and in vivo, providing survival benefit. Rai depletion is associated with alteration of multiple-signaling pathways, yet it always leads to reduced expression of proinvasive genes.

Treatment of chronic headache of cervical origin with lipostructure: an observational study.

OBJECTIVE: To test feasibility, safety, and efficacy of local transplant of stromal fraction of adipose tissue in the treatment of chronic headaches of cervical origin. BACKGROUND: Chronic headaches of cervical origin (chronic cervicogenic headache and occipital neuralgia) are characterized by persistent pain due to the involvement of the great occipital nerve, with concurrent myofascial spasm and the consequent nerve entrapment within the trapezoid tunnel. METHODS: Tolerability and effectiveness of treatment of chronic cervicogenic headaches refractory to conventional therapies were evaluated in 24 patients. The visual analog scale of pain and the medication use diary were used in the 3 months preceding treatment; moreover, in order to verify the quality of life, patients are required to fill before surgery the neck pain disability index, the headache disability index, migraine disability assessment scale questionnaire, and the short-form 12 standard v1 questionnaire. Follow-up examination was performed at 3 and 6 months. RESULTS: In 19 cases (79.2%), a good clinical response was recorded. At 6-month follow-up analysis, recurrence of occipital pain was recorded in 7 cases (29.2%); there is a significant reduction in disability and pain scores, and also a significant reduction of need for pharmacologic treatment and a fast return to previous work capacities. CONCLUSIONS: The key point of our therapeutic strategy might be the regenerative role of stromal fraction of adipose tissue transplanted in the area of the occipital nerve entrapment; the results of the present study are encouraging both in terms of reduction of pain scores and in terms of quality of life improvement. The technique is minimally invasive, and no complications were recorded; indeed, the procedure seems to be safe and effective, and thus, a randomized study with larger follow-up and in a large series will be started.

Treatment of high-grade spondylolisthesis with Schanz recoil screws: our experience.

PURPOSE: Spondylolisthesis surgical treatment is often difficult with higher degree of slip and related techniques still debated. We have taken into consideration double thread recoil Schanz screws. This system should allow the best reduction of the slip, treating only the affected vertebrae. METHODS: We retrospectively analyzed 46 patients affected by grade II or higher spondylolisthesis, treated with circumferential arthrodesis using Schanz screws. Duration of surgery, complications, reduction, and rate of fusion have been recorded. RESULTS: We found that duration of surgery and complications were similar or slightly lower if compared to our standard Posterior Lumbar Interbody Fusion procedures. However, radiological results and clinical outcome appear better in cases treated with Schanz screws. CONCLUSIONS: Fixation system with Schanz screws seems to be effective in reducing the slip, treating only the affected level, in high grade of spondylolisthesis.

Relationship between lumbar lordosis, pelvic parameters, PI-LL mismatch and outcome after short fusion surgery for lumbar degenerative disease. Literature review, rational and presentation of public study protocol: RELApSE study (registry for evaluation of lumbar artrodesis sagittal alignEment).

Background: Vertebral arthrodesis for degenerative pathology of the lumbar spine still remains burdened by clinical problems with significant negative results. The introduction of the sagittal balance assessment with the evaluation of the meaning of pelvic parameters and spinopelvic (PI-LL) mismatch offered new evaluation criteria for this widespread pathology, but there is a lack of consistent evidence on long-term outcome. Methods: The authors performed an extensive systematic review of literature, with the aim to identify all potentially relevant studies about the role and usefulness of the restoration or the assessment of Sagittal balance in lumbar degenerative disease. They present the study protocol RELApSE (NCT05448092 ID) and discuss the rationale through a comprehensive literature review. Results: From the 237 papers on this topic, a total of 176 articles were selected in this review. The analysis of these literature data shows sparse and variable evidence. There are no observations or guidelines about the value of lordosis restoration or PI-LL mismatch. Most of the works in the literature are retrospective, monocentric, based on small populations, and often address the topic evaluation partially. Conclusions: The RELApSE study is based on the possibility of comparing a heterogeneous population by pathology and different surgical technical options on some homogeneous clinical and anatomic-radiological measures aiming to understanding the value that global lumbar and segmental lordosis, distribution of lordosis, pelvic tilt, and PI-LL mismatch may have on clinical outcome in lumbar degenerative pathology and on the occurrence of adjacent segment disease.

Syndrome of inappropriate secretion of antidiuretic hormone in traumatic brain injury: when tolvaptan becomes a life saving drug.

OBJECTIVE: To outline the role of a new drug, tolvaptan, in treating severe and chronic hyponatraemia. Tolvaptan decreases aquaporin expression in renal collecting ducts, by inhibiting antidiuretic hormone (ADH)-V2 receptors, to promote free water clearance. Given its mechanism of action, this drug seems the ideal treatment for the syndrome of inappropriate antidiuretic hormone secretion (SIADH) when the osmotic imbalance leads to life threatening complications. DATA SOURCES: A case is described of severe hyponatraemia deriving from SIADH secondary to meningoencephalitis in a patient admitted to hospital for traumatic brain injury. DATA EXTRACTION: Clinical, laboratory and radiological data at presentation and for a 1 year of follow-up were analysed. DATA SYNTHESIS: Tolvaptan ameliorated hyponatraemia, brain oedema and consciousness, and drug withdrawal led to recurrence of hyponatraemia and coma. CONCLUSIONS: In patients with SIADH, which is not self-limited, and is associated with severe cognitive impairment, the use Tolvaptan may prove life saving and should be rigorously evaluated.

Degenerative Lumbar Stenosis Surgery: Predictive Factors of Clinical Outcome-Experience with 1001 Patients.

BACKGROUND: Degenerative lumbar spinal stenosis (DLSS) carries a high risk of morbidity and represents a financial burden to society. A late diagnosis can lead to severe disability. Although lumbar decompressive surgery has been widely used worldwide, the proper preoperative factors to define the ideal candidates for decompression are missing. METHODS: A total of 1001 patients who had undergone decompressive surgery from 2012 to 2019 for DLSS were screened for the presence of 9 clinical and radiological parameters. For all cases, the differences between the baseline and postoperative Oswestry disability index were calculated and the results categorized as 5 different classes (ranging from very poor outcomes to excellent outcomes) according to the specific scores. Generalized ordinal logistic regression was then used to analyze the significance of the 9 parameters (coded as dummy variables) in predicting the outcome as measured by Oswestry disability index improvement after surgery. RESULTS: Of the 9 parameters, 8 were found to be significant predictors. The radiological grade of compression was the strongest, followed by polyneuropathy, obesity, symptom duration, gait autonomy, radicular deficits, American Society of Anesthesiologists score, and level of surgery. In contrast, previous back surgery was not predictive of the outcome. CONCLUSIONS: Our findings have indicated that the ideal candidate for surgery will have the following preoperative characteristics: Schizas grade D, no signs of peripheral polyneuropathy, body mass index <30 kg/m2, symptom duration of <2 years, gait autonomy <100 m, no radicular deficits, 1 level of stenosis, and an American Society of Anesthesiologists score of 1, 2, or 3.

Vertebroplasty for pain relief and spinal stabilization in multiple myeloma.

Mechanical stabilization of oncological vertebral fractures with cement augmentation is the first mechanism of pain relief, with or without restoration of vertebral body height. The aim of this study was to assess the safety and efficacy of vertebroplasty for painful vertebral body fractures in patients with multiple myeloma, in each phase of the disease. The authors reviewed a consecutive group of patients with multiple myeloma who underwent vertebroplasty at our Institute between November 2003 and December 2005. Twenty-eight levels were performed on 11 patients during 14 treatment sessions. All patients suffered from intractable back pain, and presented various lesion types (with and without fractures of posterior wall, and with and without epidural disease). The preoperative median visual analog scale (VAS) score was 7. The median duration of symptoms was 1.1 months. Eight patients were ambulating with orthopaedic devices (57%) in the pre-treatment period. Improvement or complete pain relief was observed in all patients (immediately in 8 cases, and after 2 days in 6 cases). The median VAS pain score decreased to 2. There was no symptomatic procedure-related complication. There were three cases (21%) of PMMA leakage: in the disc space in one case (7%), and in the anterior spinal canal in two cases (14%). Complete removal of orthopaedic devices was obtained in five patients (36%). No new deformation or collapse of the treated vertebrae was observed during the follow-up (range 1 day-25 months). In conclusion, vertebroplasty is a safe and efficient procedure in the treatment of painful vertebral body fractures in patients with multiple myeloma, without potential contraindications, such as fractures of the posterior wall or epidural disease. We also treated three and more levels in 28% of cases in a single session without complications. Due to the early pain relief and the low complication rate, it is possible to expand the indication to vertebroplasty for the prophylactic augmentation of those vertebral bodies at risk of fracture in which significant neoplastic substitution of the body is present.

Expression of the transcription factor HEY1 in glioblastoma: a preliminary clinical study.

AIMS AND BACKGROUND: The hairy/enhancer of split (E(spl))-related family of transcription factors (HES and HEY) are established targets of the notch signaling pathway, which has been implicated in different developmental processes, tumor formation and the self-renewal of neural stem cells. We determined the expression of HEY1 in human malignant gliomas to investigate whether its expression might be related to prognosis. METHODS: The expression of HEY1 was studied by in situ hybridization on 62 cases of glioblastoma. Patients were treated with surgery followed by chemotherapy and radiotherapy. We considered as end points of the study the overall survival time and progression-free interval. Correlations between HEY1 expression and tumor grade/patient overall survival and free interval before recurrence were analyzed using univariate analysis. RESULTS: Based on the in situ hybridization results, HEY1 expression rate was reported as negative staining in 13 cases (20.6%), as weak staining in 11 cases (17.3%), as moderate staining in 21 cases (33.3%), and as strong staining in 17 cases. We considered in the analysis the cumulative expression of HEY1 at in situ hybridization (Hey Index) as negative in 13 cases and positive in 49 cases (77.78%). The overall survival (P = 0.002) and the free-interval (P = 0.012) were significantly longer in patients who were negative for HEY1 expression. CONCLUSIONS: Our data suggest that expression of HEY1 might be used as a marker to distinguish glioblastoma patients with a relatively good prognosis from those at high-risk, and that, in the future, HEY1 might represent a therapeutic target.

A role for the transcription factor HEY1 in glioblastoma.

Abstract Glioblastoma multiforme (GBM), the highest-grade glioma, is the most frequent tumour of the brain with a very poor prognosis and limited therapeutic options. Although little is known about the molecular mechanisms that underlie glioblastoma formation, a number of signal transduction routes, such as the Notch and Ras signalling pathways, seem to play an important role in the formation of GBM. In the present study, we show by in situ hybridization on primary tumour material that the transcription factor HEY1, a target of the Notch signalling pathway, is specifically up-regulated in glioma and that expression of HEY1 in GBM correlates with tumour-grade and survival. In addition, we show by chromatin immunoprecipitations, luciferase assays and Northern blot experiments that HEY1 is a bona fide target of the E2F family of transcription factors, connecting the Ras and Notch signalling pathways. Finally, we show that ectopic expression of HEY1 induces cell proliferation in neural stem cells, while depletion of HEY1 by RNA interference reduces proliferation of glioblastoma cells in tissue culture. Together, these data imply a role for HEY1 in the progression of GBM, and therefore we propose that HEY1 may be a therapeutic target for glioblastoma patients. Moreover, HEY1 may represent a molecular marker to distinguish GBM patients with a longer survival prognosis from those at high risk.

Randomized Trial of Sacroiliac Joint Arthrodesis Compared with Conservative Management for Chronic Low Back Pain Attributed to the Sacroiliac Joint.

BACKGROUND: Sacroiliac joint pain is increasingly recognized as a cause of low back pain. We compared the safety and effectiveness of minimally invasive sacroiliac joint arthrodesis using triangular titanium implants and conservative management in patients with chronic sacroiliac joint pain. METHODS: This study was a prospective, multicenter randomized controlled trial of adults with chronic sacroiliac joint pain assigned to either conservative management or sacroiliac joint arthrodesis with triangular titanium implants. The study end points included self-rated low back pain (visual analog scale [VAS]), back dysfunction (Oswestry Disability Index [ODI]), and quality of life. Ninety percent of subjects in both groups completed the study. RESULTS: Between June 6, 2013, and May 15, 2015, 103 subjects were randomly assigned to conservative management (n = 51) or sacroiliac joint arthrodesis (n = 52). At 2 years, the mean low back pain improved by 45 points (95% confidence interval [CI], 37 to 54 points) after sacroiliac joint arthrodesis and 11 points (95% CI, 2 to 20 points) after conservative management, with a mean difference between groups of 34 points (p < 0.0001). The mean ODI improved by 26 points (95% CI, 21 to 32 points) after sacroiliac joint arthrodesis and 8 points (95% CI, 2 to 14 points) after conservative management, with a mean difference between groups of 18 points (p < 0.0001). Parallel improvements were seen in quality of life. In the sacroiliac joint arthrodesis group, the prevalence of opioid use decreased from 56% at baseline to 33% at 2 years (p = 0.009), and no significant change was observed in the conservative management group (47.1% at baseline and 45.7% at 2 years). Subjects in the conservative management group, after crossover to the surgical procedure, showed improvements in all measures similar to those originally assigned to sacroiliac joint arthrodesis. In the first 6 months, the frequency of adverse events did not differ between groups (p = 0.664). By month 24, we observed 39 severe adverse events after sacroiliac joint arthrodesis, including 2 cases of sacroiliac joint pain, 1 case of a postoperative gluteal hematoma, and 1 case of postoperative nerve impingement. The analysis of computed tomographic (CT) imaging at 12 months after sacroiliac joint arthrodesis showed radiolucencies adjacent to 8 implants (4.0% of all implants). CONCLUSIONS: For patients with chronic sacroiliac joint pain due to joint degeneration or disruption, minimally invasive sacroiliac joint arthrodesis with triangular titanium implants was safe and more effective throughout 2 years in improving pain, disability, and quality of life compared with conservative management. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Clinical Significance of Extracellular Vesicles in Plasma from Glioblastoma Patients.

PURPOSE: Glioblastoma (GBM) is the most common primary brain tumor. The identification of blood biomarkers reflecting the tumor status represents a major unmet need for optimal clinical management of patients with GBM. Their high number in body fluids, their stability, and the presence of many tumor-associated proteins and RNAs make extracellular vesicles potentially optimal biomarkers. Here, we investigated the potential role of plasma extracellular vesicles from patients with GBM for diagnosis and follow-up after treatment and as a prognostic tool. EXPERIMENTAL DESIGN: Plasma from healthy controls (n = 33), patients with GBM (n = 43), and patients with different central nervous system malignancies (n = 25) were collected. Extracellular vesicles were isolated by ultracentrifugation and characterized in terms of morphology by transmission electron microscopy, concentration, and size by nanoparticle tracking analysis, and protein composition by mass spectrometry. An orthotopic mouse model of human GBM confirmed human plasma extracellular vesicle quantifications. Associations between plasma extracellular vesicle concentration and clinicopathologic features of patients with GBM were analyzed. All statistical tests were two-sided. RESULTS: GBM releases heterogeneous extracellular vesicles detectable in plasma. Plasma extracellular vesicle concentration was higher in GBM compared with healthy controls (P < 0.001), brain metastases (P < 0.001), and extra-axial brain tumors (P < 0.001). After surgery, a significant drop in plasma extracellular vesicle concentration was measured (P < 0.001). Plasma extracellular vesicle concentration was also increased in GBM-bearing mice (P < 0.001). Proteomic profiling revealed a GBM-distinctive signature. CONCLUSIONS: Higher extracellular vesicle plasma levels may assist in GBM clinical diagnosis: their reduction after GBM resection, their rise at recurrence, and their protein cargo might provide indications about tumor, therapy response, and monitoring.

Usefulness of corset adoption after single-level lumbar discectomy: a randomized controlled trial.

OBJECTIVE In this paper, the authors sought to verify whether corset adoption could improve the short-term and midterm outcome scores of patients after single-level lumbar discectomy. METHODS A monocentric, randomized controlled trial of 54 consecutive patients who underwent single-level lumbar discectomy at the authors' institution was performed from September 2014 to August 2015. Patients were randomly assigned to use or not use a lumbar corset in the upright position. Patients with previous interventions for disc herniation or with concomitant canal or foraminal stenosis were excluded. The visual analog scale, Oswestry Disability Index, and Roland Morris Disability Questionnaire were used to compare groups at the 1- and 6-month follow-up time points. RESULTS No significant differences between the 2 groups were reported at either time point for any given outcome irrespective of the scale used. CONCLUSIONS Corset adoption does not improve the short-term and midterm outcomes of patients after single-level lumbar discectomy.

Are Antiplatelet and Anticoagulants Drugs A Risk Factor for Bleeding in Mild Traumatic Brain Injury?

OBJECTIVE: Facing mild traumatic brain injury, clinicians must decide whether to perform a computed tomography (CT) scan to detect a potential intracranial hemorrhage. Many useful guidelines have been developed for the general population, but there is no general consensus about the best practice to adopt when dealing with patients on antiplatelet or anticoagulation drugs. The relatively recent introduction of new anticoagulants and second-generation antiplatelet drugs poses new challenges in this field. There are no data in the literature about the relative risk of intracranial bleeding in such categories. METHODS: We enrolled 2773 consecutive patients presenting at our emergency department with mild traumatic brain injury as chief complaint and evaluated the results of their head CT scans, stratifying their anticoagulation and/or antiplatelet drug regime. RESULTS: Of these patients, 1608 matched the criteria for head CT scan and had a Glasgow Coma Scale (GCS) score of 15; 517 were on antiplatelet drugs, whereas 213 were on anticoagulants. The risk of developing intracranial bleeding was significantly higher for patients on antiplatelet drugs, whereas the risk of anticoagulated patients overlapped with that of the general population. The trend for second-generation drugs was of higher risk of bleeding only for antiplatelets. CONCLUSIONS: Patients with a GCS score of 15 on long-term anticoagulation therapy seem to be at no higher risk for intracranial hemorrhage than are nonanticoagulated patients. On the contrary, patients with a GCS score of 15 on antiplatelet therapy seem to be more prone to developing intracranial bleeding than are the general population, with a trend to be more at risk when it comes to second-generation drugs.

In vitro efficacy of silk sericin microparticles and platelet lysate for intervertebral disk regeneration.

Intervertebral disk degeneration is an oxidative and inflammatory pathological condition that induces viability and functionality reduction of Nucleus Pulposus cells (NPs). Cellular therapies were previously proposed to repair and substitute the herniated disk but low proliferative index and pathological conditions of NPs dramatically reduced the efficacy of this approach. To overcome these problems we proposed, for the first time, a therapeutic system based on the association of silk sericin microparticles and platelet-derived products. Silk sericin (SS) is a bioactive protein with marked antioxidant properties, while platelet lysate (PL) and platelet poor plasma (PPP) represent a source of growth factors able to support cell viability and to promote tissue regeneration. We demonstrated that the mixture PL + PPP promoted NPs proliferation with a significant reduction of cellular doubling time. SS microparticles, alone or in combination with PPP, presented the higher ROS-scavenging activity while, SS microparticles and PL resulted as the best association able to protect NPs against oxidative stress induce by hydroxide peroxide. Based on these results, the authors are confident that, with the ever increasing need of efficacious tools for regenerative medicine purposes, SS microparticles and PL + PPP association could represent an effective approach for the development of low impact and non-invasive therapies.