Vítor M Gaspar

University of Aveiro | UA · CICECO - Centre for Research in Ceramics and Composite Materials

The co-delivery of minicircle DNA (mcDNA) and small anti-cancer drugs via stimuli-sensitive nanocarriers is a promising approach for combinatorial cancer therapy. However, the simultaneous loading of drugs and DNA in nanosized delivery systems is remarkably challenging. In this study we describe the synthesis of triblock co-polymer micelles based o...

The development of stimuli-responsive nanomedicines with tunable cargo release is gathering an increased applicability in bone regeneration and precision biomedicine. Yet, the formulation of nanocarriers that explore skeletal-specific stimuli remains remarkably challenging to materialize due to several endogenous and disease-specific barriers that...

Naringin is a naturally occurring flavanone with recognized neuroprotective, cardioprotective, anti‐inflammatory, and antiosteoporotic properties. Herein, the delivery of Naringin‐loaded methoxy‐poly(ethylene glycol)–maleimide–thiol–poly(l‐lactide) (mPEGMSPLA) diblock polymeric micelles to human adipose‐derived stem cells (hASCs) with the aim to...

Statement of significance: The ability to correctly mimic the complexity of the tumor microenvironment in vitro is a key aspect for the development of evermore realistic in vitro models for drug-screening and fundamental cancer biology studies. In this regard, conventional spheroid-based 3D tumor models, combined with spherically structured biomat...

Drug-DNA combination therapies are receiving an ever growing focus due to their potential for improving cancer treatment. However, such approaches are still limited by the lack of multipurpose delivery systems that encapsulate drugs and condense DNA simultaneously. In this study, we describe the successful formulation of gas-generating pH-responsiv...

Tissue-derived decellularized extracellular matrix (dECM) provides unique biomolecular cues for bioengineering 3D tumor models with increasingly physiomimetic features. This biomimicry potential can be expanded by combining dECM with key components of native tissues, such as glycosaminoglycans (GAGs). Yet, this combination remains highly challengin...

The androgens/androgen receptor (AR) axis is the main therapeutic target in prostate cancer (PCa). However, while initially responsive, a subset of tumors loses AR expression through mechanisms putatively associated with epigenetic modifications. In this study, we assessed the link between the presence of CpG methylation in the 5′UTR and promoter r...

Breakthroughs in precision cell surface engineering tools are supporting the rapid development of programmable living assemblies with valuable features for tackling complex biological problems. Herein, the authors overview the most recent technological advances in chemically‐ and biologically‐driven toolboxes for engineering mammalian cell surfaces...

Engineering colloidal gel inks with suitable features for fabricating robust supraparticle architectures through 3D printing may overcome the challenges of precisely controlling nanoparticles spatial distribution across multiple scales. Herein, oppositely charged proteinaceous‐polymeric nanoparticles are combined to generate multi‐component colloid...

Granular inks comprising jammed hydrogel unit building blocks are emerging as multiprogramable precursors for 3D/4D printing nonbulk hydrogel constructs. In addition to their injectability, they also exhibit high porosity when compared to bulk hydrogels, allowing more efficient nutrient transport and cell migration through the scaffold structure. H...

Breast cancer is one of the most common and well-known types of cancer among women worldwide and is the most frequent neoplasm in intact female dogs. Female dogs are considered attractive models or studying spontaneous breast cancer, whereas female rats are currently the most widely used animal models for breast cancer research in the laboratory co...

Brewer's spent yeast (BSY) mannoproteins have been reported to possess thickening and emulsifying properties. The commercial interest in yeast mannoproteins might be boosted considering the consolidation of their properties supported by structure/function relationships. This work aimed to attest the use of extracted BSY mannoproteins as a clean lab...

This study tested hyperbaric storage (25–150 MPa, for 30 days) at room-temperature (HS/RT, 18–23 °C) in order to control the development of Byssochlamys nivea ascospores in apple juice. In order to mimic commercially pasteurized juice contaminated with ascospores, thermal pasteurization (70 and 80 °C for 30 s) and nonthermal high pressure pasteuriz...

Granular hydrogels represent an emerging class of intrinsically modular multimicrogel‐based platforms with valuable features for therapeutics delivery, as well as exogenous and endogenous tissue engineering applications. Owing to their shear thinning and self‐healing properties, granular hydrogels can be injected and annealed in situ , operating as...

Pancreatic cancer exhibits a unique bioarchitecture and desmoplastic cancer-stoma interplay that governs disease progression, multi-resistance, and metastasis. Emulating the biological features and microenvironment heterogeneity of pancreatic cancer stroma in vitro is remarkably complex, yet highly desirable for advancing the discovery of innovativ...

The extracellular matrix plays a critical role in bioinstructing cellular self‐assembly and spatial (re)configuration processes that culminate in human organoids in vitro generation and maturation. Considering the importance of the supporting matrix, herein is showcased the most recent advances in the bioengineering of decellularized tissue hydroge...

Castration-resistant prostate cancer (CRPC) is an incurable form of prostate cancer (PCa), with DNMT1 and G9a being reported as overexpressed, rendering them highly attractive targets for precision medicine. CM-272 is a dual inhibitor of both methyltransferases’ activity. Herein, we assessed the response of different PCa cell lines to CM-272, in bo...

Combinatorial conjugation of organ-on-a-chip platforms with additive manufacturing technologies is rapidly emerging as a disruptive approach for upgrading cancer-on-a-chip systems towards anatomic-sized dynamic in vitro models. This valuable technological synergy has potential for giving rise to truly physiomimetic 3D models that better emulate tum...

Bioengineering close‐to‐native in vitro models that emulate tumors bioarchitecture and microenvironment is highly appreciable for improving disease modelling toolboxes. Herein, pancreatic cancer living units – so termed cancer‐on‐a‐bead models – were generated. Such user‐programmable in vitro platforms exhibit biomimetic multi‐compartmentalization...

This study reports the formulation and delivery of Hyaluronic acid-Zein (HA-Zein) nanogels loaded with Shikonin (SK) to selectively attenuate macrophage inflammasome. The self-assembled nanogels, produced by nanoprecipitation, exhibited high encapsulation efficiency, and were selectively internalized by human THP-1-derived macrophages without elici...

Engineered living materials represent a new generation of human-made biotherapeutics that are highly attractive for a myriad of medical applications. In essence, such cell-rich platforms provide encodable bioactivities with extended lifetimes and environmental multi-adaptability currently unattainable in conventional biomaterial platforms. Emerging...

Recent advances on brewer's yeast cell wall polysaccharides have unraveled exquisite structural features and diverse composition with (β1→3), (β1→6), (α1→4), (β1→4)-mix-linked glucans that are recognized to interact with different cell receptors and trigger specific biological responses. Herein, a comprehensive showcase of structure-biofunctional r...

In article number 2009619, Tiago R. Correia, João F. Mano, and co‐workers develop a new type of hybrid cells. Individual human adipose‐derived mesenchymal stem cells are partially coated with a hard silica layer and display enhanced single‐cell survival and functionality in suspension conditions. Moreover, the ability of functionalizing silica back...

The design of dynamically crosslinked hydrogel bioinks for three-dimensional (3D) bioprinting is emerging as a valuable strategy to advance the fabrication of mechanically tuneable cell-laden constructs for 3Din vitrodisease modelling and tissue engineering applications. Herein, a dynamic bioink comprising boronic acid-functionalised laminarin and...

Dynamic soft materials that have the ability to expand and contract, change stiffness, self-heal or dissolve in response to environmental changes, are of great interest in applications ranging from biosensing and drug delivery to soft robotics and tissue engineering. This book covers the state-of-the-art and current trends in the very active and ex...

Dynamic soft materials that have the ability to expand and contract, change stiffness, self-heal or dissolve in response to environmental changes, are of great interest in applications ranging from biosensing and drug delivery to soft robotics and tissue engineering. This book covers the state-of-the-art and current trends in the very active and ex...

Leveraging 4D biofabrication for engineering biomimetic living constructs is rapidly emerging as a valuable strategy for recapitulating native tissue dynamics, via on‐demand stimuli, or in a naturally evolving mode. Carefully selecting smart materials with suitable responsiveness and cell‐supporting functionalities is crucial to take full operation...

Decellularized extracellular matrix (dECM) is emerging as a valuable tool for generating 3D in vitro tumor models that better recapitulate tumor-stroma interactions. However, the development of dECM-3D heterotypic microtumors exhibiting a controlled morphology is yet to be materialized. Precisely controlling microtumors morphologic features is key...

In solid tumors, mesenchymal stem cells (MSCs) are recognized to establish complex intercommunication networks with cancer cells and to significantly influence their invasion and metastasis potential. Such bidirectional interplay occurs between both tissue resident/tumor-associated MSCs (TA-MSCs) and also tumor infiltrating MSCs (TM-MSCs) that migr...

Over recent years, the role of distinct mesenchymal stem cell populations in cancer progression has become increasingly evident. In this regard, developing in vitro preclinical tumor models capable of portraying tumor-associated mesenchymal stem cells (TA-MSCs) interactions with the tumor microenvironment (TME), cellular and extracellular component...

The manipulation of cell surfaces in anchorage‐dependent cells can help overcome difficulties presented during cell handling and application. Silica‐based protective mechanisms existing in free‐floating microorganisms may be used as inspiration for sustaining human cell survival in suspension. Gathering on this, herein human adipose‐derived mesench...

Living therapeutics approaches that exploit mesenchymal stem cells (MSCs) as nanomedicine carriers are highly attractive due to MSCs native tropism toward the 3D tumor microenvironment. However, a streamlined pre-clinical evaluation of nano-in-cell anti-cancer therapies remains limited by the lack of in vitro testing platforms for screening MSCs-3D...

Cancer‐associated pancreatic stellate cells installed in periacinar/periductal regions are master players in generating the characteristic biophysical shield found in pancreatic ductal adenocarcinoma (PDAC). Recreating this unique PDAC stromal architecture and its desmoplastic microenvironment in vitro is key to discover innovative treatments. Howe...

Manufacturing macroscale cell-laden architectures is one of the biggest challenges faced nowadays in the domain of tissue engineering. Such living constructs, in fact, pose strict requirements for nutrients and oxygen supply that can hardly be addressed through simple diffusion in vitro or without a functional vasculature in vivo. In this context,...

Leveraging 3D bioprinting for processing stem cell-laden biomaterials has unlocked a tremendous potential for fabricating living 3D constructs for bone tissue engineering. Even though several bioinks developed to date display suitable physicochemical properties for stem cell seeding and proliferation, they generally lack the nanosized minerals pres...

The establishment of tumor microenvironment using biomimetic in vitro models that recapitulate key tumor hallmarks including the tumor supporting extracellular matrix (ECM) is in high demand for accelerating the discovery and preclinical validation of more effective anticancer therapeutics. To date, ECM‐mimetic hydrogels have been widely explored f...

The development of nanocomposite hydrogels that take advantage of hierarchic building blocks is gaining increased attention due to their added functionality and numerous biomedical applications. Gathering on the unique properties of these platforms, herein we report the synthesis of bioactive nanocomposite hydrogels comprising naringin-loaded salmo...

Bone tissue disorders pose a life‐limiting and, sometimes, life‐threatening condition to millions of people worldwide. Even though there are already several treatments to manage bone disorders, only a few are fully curative. In this way, several efforts have been made to explore and develop novel and, hopefully, more efficient treatments. Within th...

Osteoporosis, Paget's disease and osteosarcoma are a few examples of bone tissue disorders that affect millions of people worldwide. These conditions can strictly limit the lifestyle of patients and may even lead to their demise. To prevent this or, at least, try to manage the situation, there are several treatments available on the market. Notwith...

The complex tissue‐specific physiology that is orchestrated from the nano‐ to the macroscale, in conjugation with the dynamic biophysical/biochemical stimuli underlying biological processes, has inspired the design of sophisticated hydrogels and nanoparticle systems exhibiting stimuli‐responsive features. Recently, hydrogels and nanoparticles have...

In article number 2000123, João F. Mano, José Paulo S. Farinha, Carlos Baleizão, and co‐workers present novel multi‐bioactive mesoporous silica nanoparticles that release calcium, phosphate, and dexamethasone to induce osteogenic differentiation of human bone marrow mesenchymal stem cells with a single‐dose administration and no further osteogenic...

Bone regeneration requires the presence of specific factors to induce the differentiation of stem cells into osteoblasts. These factors induce osteogenesis by stimulating the expression of bone-related proteins, bone cell proliferation and differentiation. Herein, bioactive mesoporous silica nanoparticles are doped with calcium and phosphate ions w...

The development of scaffold-based three-dimensional (3D) in vitro microtumor models incorporating extracellular matrix (ECM) bioinspired biomaterials enables the generation of preclinical testing platforms with higher correlation with the in vivo tumor microenvironment. Such models present considerable advantages over scaffold-free 3D spheroid cell...

The immunomodulatory activity of flavonoids is increasingly appreciated. Macrophage phospholipids (PLs) play crucial roles in cell-mediated inflammatory responses. However, little is known on how these PLs are affected upon flavonoid treatment. In this work, we have used mass-spectrometry-based lipidomics to characterize the changes in the phosphol...

Self-assembled colloidal gels are highly versatile 3D nanocluster platforms with potential to overcome the rapid clearing issues associated with standard free nanotherapeutics administration. However, the development of nanoassembled colloidal gels exhibiting autonomous multi-particle release from the bulk particle network remains elusive. Herein,...

Recent advances in the extraction and purification of decellularized extracellular matrix (dECM) obtained from healthy or malignant tissues open new avenues for engineering physiomimetic 3D in vitro tumor models, which closely recapitulate key biomolecular hallmarks and the dynamic cancer cell–ECM interactions in the tumor microenvironment. We revi...

Epigenetic alterations, as a cancer hallmark, are associated with cancer initiation, progression and aggressiveness. Considering, however, that these alterations are reversible, drugs that target epigenetic machinery may have an inhibitory effect upon cancer treatment. The traditional drug discovery pathway is time-consuming and expensive, and thus...

The precise chemical modification of marine-derived biopolymers provides a unique opportunity for fabricating a toolbox of bioactive (bio)materials with modulated physicochemical and biological properties. Herein, the β-glucan laminarin was functionalized with phenylboronic acid (PBA) moieties that impart chemical reactivity toward diol-containing...

Native human tissues are supported by a viscoelastic extracellular matrix (ECM) that can adapt its intricate network to dynamic mechanical stimuli. To recapitulate the unique ECM biofunctionality, hydrogel design is shifting from typical covalent crosslinks toward covalently adaptable networks. To pursue such properties, herein hybrid polysaccharid...

Embedded bio-printing has fostered significant advances toward the fabrication of soft complex tissue-like constructs, by providing a physical support that allows the freeform shape maintenance within the prescribed spatial arrangement, even under gravity force. Current supporting materials still present major drawbacks for up-scaling embedded 3D b...

Hydrogel-based 3D in vitro models comprising tumor ECM-mimetic biomaterials exhibit superlative potential as preclinical testing platforms for drug discovery and bioperformance screening. However, during hydrogel design and testing stages, the ideal selection between cancer cell laden 3D models or spheroid embedded hydrogel platforms remains to be...

Prostate cancer (PCa) is the second most common malignancy among men and the fifth leading cause of cancer-related death worldwide. Patients that progress to a castration-resistant prostate cancer do not benefit from any effective treatments, being in vitro studies an important method of drug screening. However, the traditional 2D cell culture meth...

Bottom‐up tissue engineering is a promising approach for designing modular biomimetic structures that aim to recapitulate the intricate hierarchy and biofunctionality of native human tissues. In recent years, this field has seen exciting progress driven by an increasing knowledge of biological systems and their rational deconstruction into key core...

The ability of flavonoids to attenuate macrophage pro-inflammatory activity and to promote macrophage-mediated resolution of inflammation is still poorly understood at the biochemical level. In this study, we have employed NMR metabolomics to assess how therapeutically promising flavonoids (quercetin, naringenin and naringin) affect the metabolism...

Metabolomics study of flavonoid-mediated immunomodulation of human macrophages

Three-dimensional (3D) in vitro tumor spheroids are becoming popular as pre-clinical platforms for testing the performance of existing drugs or for discovery of innovative anti-cancer therapeutics. This focus is correlated with in vitro 3D tumor models ability to mimic the multicellular compact structure and spatial architecture of human solid tumo...

While a continuous monitoring of temperature at the micro and nano-scales is clearly of interest in many contexts, in many others a yes or no answer to the question "did the system locally exceeded a certain temperature threshold?" can be more accurate and useful. This is the case of hard-to-detect events, such as those where temperature fluctuatio...

Quercetin-mediated immunomodulation and metabolic alterations in human THP-1 derived macrophages, as assessed by NMR-based metabolomics

Tumor suppressor p53 remains one of the most interesting therapeutic targets in cancer gene therapy due to its consistent mutation in numerous cancers. Thus, the reinstatement of the p53 expression and function can be seen as an effective alternative for cancer treatment, motivating research in this field. In this study, L-methionine matrix was use...

3D multicellular tumor spheroids (3D-MCTS) that closely mimic in vitro the complex lung tumor microenvironment (TME) are highly desirable for screening innovative anti-cancer therapeutics. Despite significant improvements in mimicking lung TME, few models have combined tumor-infiltrating mesenchymal stem cells from bone marrow (hBM-MSCs) with heter...

The use of natural compounds for treating chronic bone diseases holds remarkable potential. Among these therapeutics, naringin, a flavanone glycoside, represents one of the most promising candidates owing to its multifaceted effect on bone tissues. This review provides an up-to-date overview on naringin applications in the treatment of bone disorde...

Hollow multilayered capsules have shown massive potential for being used in the biomedical and biotechnology fields, in applications such as cellular internalization, intracellular trafficking, drug delivery, or tissue engineering. In particular, hollow microcapsules, developed by resorting to porous calcium carbonate sacrificial templates, natural...

In vitro 3D tumor microenvironment mimicking models are gathering momentum as alternatives to traditional 2D flat monolayer cultures due to their potential for recapitulating major cancer hallmarks. To fulfill such potential, it is crucial that 3D tumor testing platforms completely emulate In vitro the complex in vivo tumor niche and its cellular c...

Non-viral minicircle biopharmaceuticals have recently emerged as alternative DNA gene expression vectors with improved biological performance and a suitable safety profile. Due to its unique characteristics minicircle DNA (mcDNA) is being actively explored for a wide range of biomedical applications spanning from the formulation of prophylactic vac...

In comparison with 2D cell culture models, 3D spheroids are able to accurately mimic some features of solid tumors, such as their spatial architecture, physiological responses, secretion of soluble mediators, gene expression patterns and drug resistance mechanisms. These unique characteristics highlight the potential of 3D cellular aggregates to be...

Combinatorial therapies established on codelivery of drugs and nucleic acids are receiving increased attention due to their outstanding potential for improving cancer therapy in comparison to standalone treatments. This encouraging approach gathers the anticancer activity of chemotherapeutics and nucleic acid capacity to repair deregulated signalin...

Frequently, skin is subjected to damaging events, such as deep cuts, burns or ulcers, which may compromise the integrity of this organ. To overcome such lesions, different strategies have been employed. Among them, wound dressings aimed to re-establish skin native properties and decreased patient pain have been pursued for a long time. Herein, an e...

Introduction: Nucleic-acid-based biopharmaceuticals enclose a remarkable potential for treating debilitating or life-threatening diseases that currently remain incurable. This promising area of research envisages the creation of state-of-the-art DNA vaccines, pluripotent cells or gene-based therapies, which can be used to overcome current issues....

The co-delivery of multiple chemotherapeutics by micellar delivery systems is a valuable approach to improve cancer treatment since various disease hallmarks can be targeted simultaneously. However, the delivery of multiple drugs requires a nanocarrier structure that can encapsulate various bioactive molecules. In this study, we evaluate the sim...

Nanocarriers with a pH responsive behavior are receiving an ever growing attention due to their potential for promoting on-demand drug release and thus increase the therapeutic effectiveness of anti-tumoral pharmaceutics. However, the majority of these systems require costly, time-consuming and complex chemical modifications of materials or dru...

Purpose: Tumor targeting nanomaterials have potential for improving the efficiency of anti-tumoral therapeutics. However, the evaluation of their biological performance remains highly challenging. In this study we describe the synthesis of multifunctional nanoparticles decorated with folic acid-PEG and dual amino acid-modified chitosan (CM-PFA) co...

Three-dimensional (3D) cell culture models of solid tumors are currently having a tremendous impact in the in vitro screening of candidate anti-tumoral therapies. These 3D models provide more reliable results than those provided by standard 2D in vitro cell cultures. However, 3D manufacturing techniques need to be further optimized in order to incr...

The design of nanocarriers for delivery of drugs and nucleic-acids remains a very challenging goal due to their physicochemical differences. In addition, the reported accelerated clearance and immune response of pegylated nanomedicines highlights the necessity to develop carriers using new materials. Herein, we describe the synthesis of amphiphilic...

The growing need to treat bone-related diseases in an elderly population compels the development of novel bone substitutes to improve patient quality of life. In this context, the advent of affordable and effective rapid prototyping equipment, such as the Fab@home plotter, has contributed to the development of novel scaffolds for bone tissue engine...

Cancer multi-drug resistance is a major issue associated with current anti-tumoral therapeutics. In this work, Crizotinib an anti-tumoral drug approved for the treatment of non-small lung cancer in humans, and Sildenafil (Viagra(®)), were loaded into micellar carriers to evaluate the establishment of a possible synergistic anti-tumoral effect in br...

Minicircular DNA (mcDNA) biopharmaceuticals have recently risen as a valuable alternative for the development of a next generation of bioactive therapeutics because they are more efficient and safer than standard plasmid DNA (pDNA). To date, the relatively insufficient knowledge regarding mcDNA biosynthesis is currently hindering its manufacture in...

The regeneration of large bone defects remains a challenging scenario from a therapeutic point of view. In fact, the currently available bone substitutes are often limited by poor tissue integration and severe host inflammatory responses, which eventually lead to surgical removal. In an attempt to address these issues, herein we evaluated the impor...

Non-steroidal anti-inflammatory drugs (NSAIDS) are emerging as a particularly valuable class of drugs due to their recently reported anti-tumoral activity in colorectal cancer. However, despite this tremendous potential, their bioavailability at the tumor microenvironment remains rather limited. To overcome this issue, in this work we synthesized b...