Mauro Alini

AO Foundation · AO Research Institute Davos (ARI)

Animal models have been invaluable in the identification of molecular events occurring in and contributing to intervertebral disc (IVD) degeneration and important therapeutic targets have been identified. Some outstanding animal models (murine, ovine, chondrodystrophoid canine) have been identified with their own strengths and weaknesses. The llama...

Background Osteoarthritis (OA) is the most common degenerative joint disease, mainly affecting the elderly worldwide, for which the drug treatment remains a major challenge. Low-grade inflammation plays a pivotal role in OA onset and progression. Exploration of notable anti-inflammatory and disease-modifying drugs on human samples could facilitate...

Introduction: Cell transplantation shows promising results for intervertebral disc (IVD) repair, however, contemporary strategies present concerns regarding needle puncture damage, cell retention, and straining the limited nutrient availability. Mesen- chymal stromal cell (MSC) homing is a natural mechanism of long-distance cellular migration to si...

The 1,9-dimethylmethylene blue (DMMB) assay enables the detection of sulfated glycosaminoglycans (sGAGs). This assay can be used to quickly quantify the sGAG content in a large number of samples using spectrophotometry. While this widespread assay appears straightforward, there are certain pitfalls that need to be considered.

Low back pain is a clinically highly relevant musculoskeletal burden and is associated with inflammatory as well as degenerative processes of the intervertebral disc. However, the pathophysiology and cellular pathways contributing to this devastating condition are still poorly understood. Based on previous evidence, we hypothesize that tissue renin...

Diarthrodial joint diseases, affecting hundreds of millions of people worldwide, mainly include osteoarthritis and cartilage injuries. No consensus on joint disease models has been achieved so far owing to the complex aetiologies, pathophysiological mechanisms and heterogeneity of disorders. The disease models established using isolated chondrocyte...

Low back pain is a clinically highly relevant musculoskeletal burden and is associated with inflammatory as well as degenerative processes of the intervertebral disc. However, the pathophysiology and cellular pathways contributing to this devastating condition are still poorly understood. Based on previous evidence, we hypothesize that tissue renin...

A new generation of bioreactors with integrated six degrees of freedom (6 DOF) aims to mimic more accurately the natural intervertebral disc (IVD) load. We developed and validated in a biological and mechanical study a specimen holder and corresponding ex vivo IVD organ model according to the bioreactor requirements for multiaxial loading and a lon...

Background and Objectives: Commonly being the first step in trauma routine imaging, up to 67% fractures are missed on plain radiographs of the thoracolumbar (TL) spine. The aim of this study was to develop a deep learning model that detects traumatic fractures on sagittal radiographs of the TL spine. Identifying vertebral fractures in simple radiog...

Background: During the intervertebral disc (IVD) degeneration process, initial degenerative events occur at the extracellular matrix level, with the appearance of neoepitope peptides formed by the cleavage of aggrecan and collagen. This study aims to elucidate the spatial and temporal alterations of aggrecan and collagen neoepitope level during IV...

The tumor microenvironment (TME), consisting of extracellular matrix, proteins, stromal cells, and a vascular system, is reported to have a key role in cancer progression and prognosis. Thereby, the interaction between the vascular network and tumor mass is an important feature of the TME since the anticancer agents which are delivered to the TME c...

Osteoarthritis (OA) is one of the most common musculoskeletal degenerative diseases and contributes to heavy socioeconomic burden. Current pharmacological and conventional non-pharmacological therapies aim at relieving the symptoms like pain and disability rather than modifying the underlying disease. Surgical treatment and ultimately joint replace...

Introduction Non-unions remain a clinical problem and are characterised by the failure to heal after a defined period of time. Current preclinical non-union models apply a wide variety of techniques to diminish intrinsic healing potential deviating from the clinical situation. The aim of this study was to develop and characterise a non-union model...

Extracellular vesicles (EVs) are advanced therapeutic strategies that can be used to efficiently treat diseases. Promising features of EVs include their innate therapeutic properties and ability to be engineered as targeted drug delivery systems. However, regulation of EV uptake is one challenge of EV therapy that must be overcome to achieve an eff...

Articular cartilage injuries are a clinically relevant problem without a clinically acceptable solution. Cartilage has a limited self-repair capacity, with damaged tissue usually replaced by fibrocartilage. Tissue engineering of cartilage is a major area of research and development, with the purpose of supporting the formation of repair tissue that...

Osteoarthritis (OA) is the most common degenerative joint disease without clear pathophysiological mechanism and effective drugs for treatment. Although various animal models exist, the translation of the outcome into clinics remains difficult due to species differences. In this study, an ex vivo inflammatory OA model was induced using different co...

Objective Resource allocation to research activities is challenging and there is limited evidence to justify decisions. Members of AO Spine were surveyed to understand the research practices and needs of spine surgeons worldwide. Methods An 84-item survey was distributed to the AO Spine community in September of 2020. Respondent demographics and i...

INTRODUCTION: Low back pain is the main reason for disability worldwide leading to an immense socioeconomic burden for the affected individuals and health care systems. Degeneration of the intervertebral disc (IVD) is known to be a major cause of low back pain. Recently, we showed that effector molecules of the tissue renin- angiotensin system (tRA...

Objectives: Low back pain is the main reason for disability worldwide, and degeneration of the intervertebral disc (IDD) is a major cause. Numerous recent studies have described local renin-angiotensin systems in human tissues and indicated that they contain pathological and protective components involved in balancing the cells' inflammatory state....

Annulus fibrosus (AF) tissue engineering is a promising strategy for repairing the degenerated intervertebral disc (IVD) and a research area that could benefit from improved tissue models to drive translation. AF tissue is composed of concentric layers of aligned collagen bundles arranged in an angle-ply pattern, an architecture which is challengin...

Tissue engineering is rapidly progressing toward clinical application. In the musculoskeletal field, there has been an increasing necessity for bone and cartilage replacement. Despite the promising translational potential of tissue engineering approaches, careful attention should be given to the quality of developed constructs to increase the real...

The aim of this work is to investigate the capability of PRP as an adjuvant therapy to autologous chondrocyte implantation (ACI) in combination with multi-axial load with respect to cartilage regeneration. Articular cartilage shows poor repair capacity and therapies for cartilage defects are still lacking. Well-established operative treatments incl...

The mouse outer annulus fibrosus (AF) was previously shown to contain CD146+ AF cells, while in vitro culture and exposure to transforming growth factor‐beta (TGF‐β) further increased the expression of CD146. However, neither the specific function of CD146 nor the underlying mechanism of TGF‐β upregulation of CD146+AF cells have been elucidated yet...

Hyaluronic acid (HA) is a key component of the intervertebral disc (IVD) that is widely investigated as an IVD biomaterial. One persisting challenge is introducing materials capable of supporting cell encapsulation and function, yet with sufficient mechanical stability. In this study, a hybrid interpenetrating polymer network (IPN) was produced as...

Musculoskeletal disorders are the most common reason of chronic pain and disability representing worldwide an enormous socio-economic burden. In this review, new biomedical application fields for Raman spectroscopy (RS) technique related to skeletal tissues are discussed showing that it can provide a comprehensive profile of tissue composition in s...

Chronic discogenic back pain is associated with increased inflammatory cytokine levels that can influence the proximal peripheral nervous system, namely the dorsal root ganglion (DRG). However, transition to chronic pain is widely thought to involve glial activation in the spinal cord. In this study, an in vitro model was used to evaluate the commu...

In the field of tissue engineering, progress has been made towards the development of new treatments for cartilage and bone defects. However, in vitro culture conditions for human bone marrow mesenchymal stromal cells (hBMSCs) have not yet been fully defined. To improve our understanding of cartilage and bone in vitro differentiation, we investigat...

The osteogenic microenvironment of bone-repairing materials plays a key role in accelerating bone regeneration but remains incompletely defined, which significantly limits the application of such bioactive materials. Here, the transcriptional landscapes of different osteogenic microenvironments, including three-dimensional (3D) hydroxyapatite (HA)...

Biodegradable and bioresponsive polymer-based nanoparticles (NPs) can be used for oligonucleotide delivery, making them a promising candidate for mRNA-based therapeutics. In this study, we evaluated and optimized the efficiency of a cationic, hyperbranched poly(amidoamine)s-based nanoparticle system to deliver tdTomato mRNA to primary human bone ma...

In the field of regenerative medicine, considerable advances have been made from the technological and biological point of view. However, there are still large gaps to be filled regarding translation and application of mesenchymal stromal cell (MSC)-based therapies into clinical practice. Indeed, variables such as cell type, unpredictable donor var...

In vitro models aim to recapitulate the in vivo situation. To more closely mimic the knee joint environment, current in vitro models need improvements to reflect the complexity of the native tissue. High molecular weight hyaluronan (hMwt HA) is one of the most abundant bioactive macromolecules in healthy synovial fluid, while shear and dynamic comp...

Low back pain (LBP) is a commonly experienced symptom posing a tremendous healthcare burden to individuals and society at large. The LBP pathology is strongly linked to degeneration of the intervertebral disc (IVD), calling for development of early-stage diagnostic tools for visualizing biomolecular changes in IVD. Multimodal measurements of fluore...

Background context Traumatic thoracolumbar (TL) fractures are frequently encountered in emergency rooms. Sagittal and anteroposterior radiographs are the first step in the trauma routine imaging. Up to 30% of TL fractures are missed in this imaging modality, thus requiring a CT and/or MRI to confirm the diagnosis. A delay in treatment leads to incr...

Despite the huge body of research on osteogenic differentiation and bone tissue engineering , the translation potential of in vitro results still does not match the effort employed. One reason might be that the protocols used for in vitro research have inherent pitfalls. The synthetic glucocor-ticoid dexamethasone is commonly used in protocols for...

Introduction The goal of this study is to characterize transcriptome changes and gene regulation networks in an organ culture system that mimics early post‐traumatic intervertebral disc (IVD) degeneration. Methods To mimic a traumatic insult, bovine caudal IVDs underwent one strike loading. The control group was cultured under physiological loadin...

Evidence has arisen in recent years suggesting that a tissue renin-angiotensin system (tRAS) is involved in the progression of various human diseases. This system contains two regulatory pathways: a pathological pro-inflammatory pathway containing the Angiotensin Converting En- zyme (ACE)/Angiotensin II (AngII)/Angiotensin II receptor type 1 (AGTR1...

The purpose of the present pilot study was to evaluate the effect of a hydrogel composed of hyaluronic acid (HA) and platelet-rich plasma (PRP) as a carrier for human mesenchymal stem cells (hMSCs) for intervertebral disc (IVD) regeneration using a disc organ culture model. HA was mixed with batroxobin (BTX) and PRP to form a hydrogel encapsulating...

Novel approaches, combining technology, biomaterial design, and cutting-edge cell culture, have been increasingly considered to advance the field of tissue engineering and regenerative medicine. Within this context, acoustic manipulation to remotely control spatial cellular organisation within a carrier matrix has arisen as a particularly promising...

Symptomatic intervertebral disc (IVD) degeneration (IDD) is a major socioeconomic burden and is characterized by inflammation and tissue degradation. Due to the lack of causative therapies, there is an urgent need for innovative experimental organ culture models to study the mechanisms involved in the progression of the disease, find therapeutic ta...

PurposeLumbar Modic change (MC) can serve as a diagnostic marker as well as an independent source of chronic low back pain (CLBP). This study aimed to test for the existence of serum biomarkers in CLBP patients with MC.Methods Age- and sex-matched CLBP patients with confirmed MC on lumbar MRI (n = 40) and pain-free controls (n = 40) were assessed....

Background Mesenchymal stromal cells (MSCs) have been introduced as promising cell source for regenerative medicine. Besides their multilineage differentiation capacity, MSCs release a wide spectrum of bioactive factors. This secretome holds immunomodulatory and regenerative capacities. In intervertebral disc (IVD) cells, application of MSC secreto...

The repair of focal cartilage defects remains one of the foremost issues in the field of orthopaedics. Chondral defects may arise from a variety of joint pathologies and left untreated, will likely progress to osteoarthritis. Current repair techniques, such as microfracture, result in short-term clinical improvements but have poor long-term outcome...

Articular cartilage injury and repair is an issue of growing importance. Although common, defects of articular cartilage present a unique clinical challenge due to its poor self-healing capacity, which is largely due to its avascular nature. There is a critical need to better study and understand cellular healing mechanisms to achieve more effectiv...

Citation: Saravi, B.; Li, Z.; Pfannkuche, J.; Wystrach, L.; Häckel, S.; E. Albers, C.; Grad, S.; Alini, M.; Richards, R.G.; Lang, C.; et al. Publisher's Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Abstract: Our recent study detected the expression of a tissue renin-angiotensin syst...

Low back pain (LBP) is a major reason for disability, and symptomatic intervertebral disc (IVD) degeneration (IDD) contributes to roughly 40% of all LBP cases. Current treatment modalities for IDD include conservative and surgical strategies. Unfortunately, there is a significant number of patients in which conventional therapies fail with the resu...

Circulating microRNAs (miRNAs) have been associated with various degenerative diseases, including intervertebral disc (IVD) degeneration. Lumbar disc herniation (LDH) often occurs in young patients, although the underlying mechanisms are poorly understood. The aim of this work was to generate RNA deep sequencing data of peripheral blood samples fro...

Our recent study detected the expression of a tissue Renin-Angiotensin System (tRAS) in human intervertebral discs (IVDs). The present study sought to investigate the impact of angiotensin II receptor type 1 (AGTR1) antagonist losartan on human nucleus pulposus (NP) cell inflammation and degeneration induced by tumor necrosis factor-α (TNF-α). Huma...

Injury of articular cartilage leads to an imbalance in tissue homeostasis, and due to the poor self-healing capacity of cartilage the affected tissue often exhibits osteoarthritic changes. In recent years, injectable and highly tunable composite hydrogels for cartilage tissue engineering and drug delivery have been introduced as a desirable alterna...

The recent convergence of decellularized extracellular matrix (dECM) methodologies and 3D bioprinting (3DBP) has led to multiple advancements in tissue engineering scaffold design by enabling researchers to recreate a tissue‐specific 3D environment in a custom geometry. The application of 3DBP of dECM for articular cartilage and intervertebral disc...