Lorenzo Moroni

Maastricht Universiteit · Complex Tissue Regeneration

Chronic kidney disease (CKD) ranks as the twelfth leading cause of death worldwide and represents a major global health problem with still rather limited treatment options. The development of new in vitro models replicating defined segments of the kidney functional units, i.e., the nephrons, in a physiologically relevant and reproducible manner cou...

Today, cartilage tissue engineering (CTE) is considered important due to the lack of repair of cartilaginous lesions and the absence of appropriate methods for treatment. In this study, polycaprolactone (PCL) scaffolds were fabricated by three-dimensional (3D) printing and were then coated with fibrin (F) and acellular solubilized extracellular mat...

The main function of articular cartilage is to provide a low friction surface and protect the underlying subchondral bone. The extracellular matrix composition of articular cartilage mainly consists of glycosaminoglycans and collagen type II. Specifically, collagen type II fibers have an arch-like organization that can be mimicked with segments of...

Citation: Ursini, O.; Grieco, M.; Sappino, C.; Capodilupo, A.L.; Giannitelli, S.M.; Mauri, E.; Bucciarelli, A.; Coricciati, C.; de Turris, V.; Gigli, G.; et al. Modulation of Methacrylated Hyaluronic Acid Hydrogels Enables Their Use as 3D Cultured Model. Gels 2023, 9, 801. Abstract: Bioengineered hydrogels represent physiologically relevant platfor...

Introduction Phthalates are a class of endocrine-disrupting chemicals that have been shown to negatively correlate with thyroid hormone serum levels in humans and to cause a state of hyperactivity in the thyroid. However, their mechanism of action is not well described at the molecular level. Methods We analyzed the response of mouse thyroid organ...

Bone marrow‐derived mesenchymal stromal cells (BMSCs) are extensively being utilized for cartilage regeneration owing to their excellent differentiation potential and availability. However, controlled differentiation of BMSCs towards cartilaginous phenotypes to heal full‐thickness cartilage defects remains challenging. This study investigates how d...

Conventional synthetic hydrogels often lack the load-bearing capacity and mechanical properties of native biopolymers found in tissue, such as cartilage. In natural tissues, like cartilage, toughness is often imparted via the combination of fibrous non-covalent self-assembly with key covalent bond formation. The controlled combination of supramolec...

Coronary artery disease affects millions worldwide. Bypass surgery remains the gold standard; however, autologous tissue is not always available. Hence, the need for an off-the-shelf graft to treat these patients remains extremely high. Using melt spinning, we describe here the fabrication of tubular scaffolds composed of microfibers aligned in the...

Fibrosis of implants remains a significant challenge in the use of biomedical devices and tissue engineering materials. Antifouling coatings, including synthetic zwitterionic coatings, have been developed to prevent fouling and cell adhesion to several implantable biomaterials. While many of these coatings need covalent attachment, a conceptually s...

Alginate (ALG) is a widely used biomaterial to create artificial extracellular matrices (ECM) for tissue engineering. Since it does not degrade in the human body, imparting proteolytic sensitivity to ALG hydrogels leverages their properties as ECM-mimics. Herein, we explored the strain-promoted azide-alkyne cycloaddition (SPAAC) as a biocompatible...

Mesenchymal stem cell (MSC) therapies have been brought forward as a promising treatment modality for cutaneous wound healing. However, current approaches for stem cell delivery have many drawbacks, such as lack of targetability and cell loss, leading to poor efficacy of stem cell therapy. To overcome these problems, in the present study, we develo...

Bioprinting in space is the next frontier in tissue engineering. In the absence of gravity, novel opportunities arise, as well as new challenges. The cardiovascular system needs particular attention in tissue engineering, not only to develop safe countermeasures for astronauts in future deep and long-term space missions, but also to bring solutions...

Nucleic acids have clear clinical potential for gene therapy. Plasmid DNA (pDNA) was the first nucleic acid to be pursued as a therapeutic molecule. Recently, mRNA came into play as it offers improved safety and affordability. In this study, we investigated the uptake mechanisms and efficiencies of genetic material by cells. We focused on three mai...

Traditional synthetic covalent hydrogels lack the native tissue dynamics and hierarchical fibrous structure found in the extracellular matrix (ECM). These dynamics and fibrous nanostructures are imperative in obtaining the correct cell/material interactions. Consequently, the challenge to engineer functional dynamics in a fibrous hydrogel and recap...

In recent years, engineering biomimetic cellular microenvironments have been a top priority for regenerative medicine. Collagen II, which is arranged in arches, forms the predominant fiber network in articular cartilage. Due to the shortage of suitable microfabrication techniques capable of producing 3D fibrous structures, in vitro replication of t...

Cartilage tissue presents low self-repair capability and lesions often undergo irreversible progression. Structures obtained by tissue engineering, such as those based in extrusion bioprinting of constructs loaded with stem cell spheroids may offer valuable alternatives for research and therapeutic purposes. Human mesenchymal stromal cell (hMSC) sp...

Recent technological advances in the field of Additive Manufacturing (AM) and the increasing need in Regenerative Medicine (RM) for devices that better and better mimic native tissues architecture are showing limitations in the current scaffolds fabrication techniques. A switch from the typical layer-by-layer approach is needed to achieve precise c...

The dual role of macrophages in the healing process depends on macrophage ability to polarize into phenotypes that can propagate inflammation or exert anti-inflammatory and tissue-remodeling functions. Controlling scaffold geometry has been proposed as a strategy to influence macrophage behavior and favor the positive host response to implants. Her...

Digital light processing (DLP) is an accurate and fast additive manufacturing technique to produce a variety of products, from patient‐customized biomedical implants to consumer goods. However, DLP's use in tissue engineering has been hampered due to a lack of biodegradable resin development. Herein, a library of biodegradable poly(esters) capped w...

The topography of the extracellular matrix (ECM) is a major biophysical regulator of cell behavior. While this has inspired the design of cell-instructive biomaterials, the ability to present topographic cues to cells in a true 3D setting remains challenging, particularly in ECM-like hydrogels made from a single polymer. Herein, we report the desig...

Anterior cruciate ligament (ACL) is the connective tissue providing mechanical stability to the knee joint. ACL reconstruction upon rupture remains a clinical challenge due to the high mechanical properties required for proper functioning. ACL owes its outstanding mechanical properties to the arrangement of the ECM and to the cells with distinct ph...

[This corrects the article DOI: 10.1016/j.mex.2019.10.018.].

Critical-sized bone defects, caused by congenital disorders or trauma, are defects that will not heal spontaneously and require surgical intervention. Recent advances in biomaterial design for the treatment of such defects focus on improving their osteoinductive properties. Here, we propose a bioactive composite with high ceramic content composed o...

The combination of biomaterials and bioactive particles has shown to be a successful strategy to fabricate electrospun scaffolds for bone tissue engineering. Among the range of bioactive particles, hydroxyapatite and mesoporous bioactive glasses (MBGs) have been widely used for their osteoconductive and osteoinductive properties. Yet, the compariso...

Phosphodiesterase 4 (PDE4) inhibitors have been extensively researched for their anti-inflammatory and neuroregenerative properties. Despite the known neuroplastic and myelin regenerative properties of nonselective PDE4 inhibitors on the central nervous system, the direct impact on peripheral remyelination and subsequent neuroregeneration has not y...

Human presence in space has uncovered several health concerns related to the space environment that need to be addressed for future space missions. The hostile space environment includes radiation and microgravity that cause various pathophysiological effects. Among them are conditions related to the cardiovascular system. The cardiovascular system...

The tympanic membrane (TM), is a thin tissue lying at the intersection of the outer and the middle ear. TM perforations caused by traumas and infections often result in a conductive hearing loss. Tissue engineering has emerged as a promising approach for reconstructing the damaged TM by replicating the native material characteristics. In this regar...

Organ-on-a-chip devices have enabled major breakthroughs in biomedical research, but they have yet to be successfully translated to the pharmaceutical industry. Traditional microfluidic devices rely on irreversible bonding techniques to seal fluidic channels, which limit their accessibility and automation and can be labour-intensive to operate. New...

The thyroid is a glandular tissue in the human body in which the function can be severely affected by endocrine disrupting chemicals (EDCs). Current in vitro assays to test endocrine disruption by chemical compounds are largely based on 2D thyroid cell cultures, which often fail to precisely evaluate the safety of these compounds. New and more adva...

Bone tissue engineering (BTE) is in active search of the ideal scaffold to give a clinical solution for bone regeneration in non-union fractures. During the last decades, the use of additive manufacturing (AM), and, in particular, melt extrusion AM (ME-AM), has been investigated towards this aim. ME-AM enables the fabrication of personalized 3D sca...

Melt extrusion-based additive manufacturing (AM) is often used to fabricate scaffolds for osteochondral (OC) regeneration. However, there are two shortcomings associated with this scaffold manufacturing technique for engineering of tissue interfaces: (1) most polymers used in the processing are bioinert, and (2) AM scaffolds often contain discrete...

The main function of articular cartilage is to provide a low friction surface and protect the underlying subchondral bone. The extracellular matrix composition of articular cartilage mainly consists of glycosaminoglycans and collagen type II. Specifically the collagen type II organization has a characteristic organization in three distinct zones; (...

4D Printed Shape‐Morphing Biocompatible Materials with Unpaired Movements 4D printed shape‐morphing materials allow for remote and reversible actuation of pre‐defined structures. In article number 2202539, Lorenzo Moroni and co‐workers demonstrate that these reversible actuation can be programed to display patterns of attraction and repulsion withi...

Despite tissue engineering advances, current nerve guidance conduits (NGCs) are still failing in repairing critical-sized defects. This study aims, therefore, at tackling large nerve gaps (2 cm) by designing NGCs possessing refined physicochemical properties enhancing the activity of Schwann cells (SCs) that support nerve regeneration over long dis...

Sensory innervation of the skin is essential for its function, homeostasis and wound healing mechanisms. Thus, to adequately model the cellular microenvironment and function of native skin, in vitro human skin equivalents (hSE) containing a sensory neuron population began to be researched. In this work, we established a fully human three-dimensiona...

Organ-on-chip and Lab-on-chip are microfluidic devices widely applied in the biomedical field. They are traditionally produced by soft lithography: starting from a mold fabricated by optical photolithography, a Polydimethylsiloxane (PDMS) device is obtained by casting and baking. While this technique offers the possibility to produce features with...

Bone fractures are one of the most common traumatic large-organ injuries and although many fractures can heal on their own, 2-12% of fractures are slow healing or do not heal (nonunions). Autologous grafts are currently used for treatment of nonunions but are associated with limited healthy bone tissue. Tissue engineered cell-based products have pr...

Silkworm silk protein fibroin and spider silk spidroin are known biocompatible and natural biodegradable polymers in biomedical applications. The presence of β-sheets in silk fibroin and spider spidroin conformation improves their mechanical properties. The strength and toughness of pure recombinant silkworm fibroin and spidroin are relatively low...

Synthetic biodegradable materials are commonly used to create constructs for medical devices and tissue engineered constructs. However, many of the homopolymers used in FDA approved devices such as poly(ε-caprolactone) (PCL), poly(lactic acid), or poly(carbonates) lack biogically relevant functional groups to steer biological responses in a control...

Background: Several factors like three-dimensional microstructure, growth factors, cytokines, cell-cell communication, and coculture with functional cells can affect the stem cells behavior and differentiation. The purpose of this study was to investigate the potential of decellularized placental sponge as adipose-derived mesenchymal stem cells (A...

Few synthetic hydrogels can mimic both the viscoelasticity and supramolecular fibrous structure found in the naturally occurring extracellular matrix (ECM). Furthermore, the ability to control the viscoelasticity of fibrous supramolecular hydrogel networks to influence cell culture remains a challenge. Here, we show that modular mixing of supramole...

Synthetic thermoplastic polymers are a widespread choice as material candidates for scaffolds for tissue engineering (TE), thanks to their ease of processing and tunable properties with respect to biological polymers. These features made them largely employed in melt-extrusion based additive manufacturing (AM), with particular application in hard-t...

Nerves and blood vessels are present in most organs and are indispensable for their function and homeostasis. Within these organs, neurovascular (NV) tissue forms congruent patterns and establishes vital interactions. Several human pathologies, including diabetes type II, produce NV disruptions with serious consequences that are complicated to stud...

Tissue-engineered constructs are currently limited by the lack of vascularization necessary for the survival and integration of implanted tissues. Hydrogen sulfide (H2S), an endogenous signaling gas (gasotransmitter), has been recently reported as a promising alternative to growth factors to mediate and promote angiogenesis in low concentrations. Y...

The complexity of the tumor microenvironment (TME) together with the development of the metastatic process are the main reasons for the failure of conventional anticancer treatment. In recent years, there is an increasing need to advance towards advanced in vitro models of cancer mimicking TME and simulating metastasis in order to understand the as...

The development of a well-designed tissue-engineered blood vessel (TEBV) still remains a challenge. In recent years, approaches in which the host response to implanted biomaterials is used to generate vascular constructs within the patient's body have gained increasing interest. The delivery of growth factors to these in situ-engineered vascular gr...

Shape morphing materials, especially those fabricated by 4D printing, are gaining much attention due to their versatility of actuation and capability of being programmed in advance. These materials become particularly interesting for biomedical applications where implant materials could be remotely actuated, exerting a force on the surrounding tiss...

Vascular endothelial growth factor (VEGF) plays a vital role in promoting attachment and proliferation of endothelial cells, and induces angiogenesis. In recent years, much research has been conducted on functionalization of tissue engineering scaffolds with VEGF or VEGF-mimetic peptide to promote angiogenesis. However, most chemical reactions are...

Smooth muscle cells play a pivotal role in maintaining blood pressure and remodeling of the extracellular matrix. These cells have a characteristic spindle shape and are aligned in the radial direction to aid in the constriction of any artery. Tissue engineered grafts have the potential to recreate this alignment and offer a viable alternative to t...

A 3D in vitro model of innervated skin would be a useful tool in dermatological research to study the effect of different chemicals and compounds on the sensory properties of skin. Current innervated skin models are limited in composition and often composed of ex vivo skin explants and/or animal-derived material. In this study, our aim was to devel...

Additive manufacturing technology is a growing field, which demands advanced chemistry and fabrication process if smart-materials are desired. Herein, the concept of jammed microgels designed with a new crosslinking method is introduced to be used in 3D-printing applications. Jammed microgels decorated with superficial hydrophobic segments and pure...

Pluripotent stem cell‐derived kidney organoids offer a promising solution to renal failure, yet current organoid protocols often lead to off‐target cells and phenotypic alterations, preventing maturity. Here, various dynamic hydrogel architectures are created, conferring a controlled and biomimetic environment for organoid encapsulation. How hydrog...

The field of bone tissue engineering seeks to mimic the bone extracellular matrix composition, balancing the organic and inorganic components. In this regard, additive manufacturing (AM) of high content calcium phosphate (CaP)-polymer composites holds great promise towards the design of bioactive scaffolds. Yet, the biological performance of such s...

The neurovascular system (NVS) is a complex anatomic-functional unit that synergically works to maintain organs/tissues homeostasis of the entire body. NVS alterations have recently emerged as a common distinct feature in the pathogenesis of several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Despite their undeniable...

It is estimated that by 2050 one in every ten people will be suffering from disabling hearing loss. Perforated tympanic membranes (TMs) are the most common injury to the human ear, resulting in a partial or complete hearing loss due to inept sound conduction. Commonly known as the eardrum, the TM is a thin, concave tissue of the middle ear that cap...

3D cell culture models in the form of spheroids are undoubtedly the best approach to understand the complex cellular physiological mechanisms. These structures have been used in a plethora of applications, spanning from pharmaceutical to regenerative medicine, showing potential for complete tissue and organ development. All these different applicat...

Three-dimensional cellular aggregates can mimic the natural microenvironment of tissues and organs and obtaining them through controlled and reproducible processes is mandatory for scaling up and implementing drug cytotoxicity and efficacy tests, as well as tissue engineering protocols. The purpose of this work was to develop and evaluate the perfo...

α-Amino acid based polyester amides (PEAs) are promising candidates for additive manufacturing (AM), as they unite the flexibility and degradability of polyesters and good thermomechanical properties of polyamides in one structure. Introducing α-amino acids in the PEA structure brings additional advantages such as (i) good cytocompatibility and bio...

Nowadays, there is an ever-increasing interest in the development of systems able to guide and influence cell activities for bone regeneration. In this context, we have explored for the first time the combination of type-I collagen and superparamagnetic iron oxide nanoparticles (SPIONs) to design magnetic and biocompatible electrospun scaffolds. Fo...