João F. Mano

• CEng, PhD, DSc
• Professor at University of Aveiro

Cancer‐associated fibroblasts are increasingly recognized to have a high impact on prostate tumor growth and drug resistance. Here, we bioengineered organotypic prostate cancer 3D in vitro models to better understand tumor‐stroma interplay, the metabolomic profile underlying such interactions, and their impact on standard‐of‐care therapeutics perfo...

The increasing demand for biofabricating human tissue analogs for therapeutic applications has encouraged the pursuit of innovative techniques that shift from conventional bioprint‐to‐use approaches toward instantaneous bioprint‐cryopreserve strategies. Such enabling concepts and next‐generation technologies open new possibilities for fabricating s...

Recapitulating the biophysical and biochemical complexity of the extracellular matrix (ECM) remains a major challenge in tissue engineering. Hydrogels derived from decellularized ECM provide a unique opportunity to replicate the architecture and bioactivity of native ECM, however, they exhibit limited long-term stability and mechanical integrity. I...

More recently, single‐cell encapsulation emerged as a promising field in biomedicine due to its potential applications, in cell analysis and therapy. Traditional techniques involve embedding cells in crosslinked polymers to create continuous microgels, suitable mainly for adherent cells, or encapsulating them in droplets for only short‐term analysi...

Emerging genome editing and synthetic biology toolboxes can accurately program mammalian cells behavior from the inside-out. Such engineered living units can be perceived as key building blocks for bioengineering mammalian cell-dense materials, with promising features to be used as living therapeutics for tissue engineering or disease modeling appl...

Soft liquified capsules are explored for various biotechnological applications owing to their versatility and protective nature. However, it is challenging to assess and control their internal environment post‐production without compromising their structural integrity. This study explores liquid capsules with shells created from gelatin modified wi...

MicroRNAs (miRNAs) are short non-coding RNA molecules involved in post-transcriptional control. They are closely related to cancer-associated processes, making them promising candidates for diagnostic and prognostic biomarkers, as well as targets for cancer therapy. This study investigated the expression levels of let-7b, miR-29b, miR-125b, and miR...

Microfluidic organ-on-chip systems are promising platforms for the development of biomimetic models that aim to reconstruct the 3D architecture and intrinsic functionality of native tissues. An in-depth comprehension of the pivotal role of extracellular matrix in intricate cellular responses has paved the way for the emergence of biologically-relev...

Introduction Ink engineering can advance 3D-printability for better therapeutics, with optimized proprieties. Herein, we describe a methodology for yielding 3D-printable nanocomposite inks (NC) using low-viscous matrices, via the interaction between the organic and inorganic phases by chemical coupling. Method Natural photocurable matrices were sy...

This study proposes a tunable ink engineering methodology to allow 3D printing processability of highly bioactive but otherwise low‐viscous and unprintable blood‐derived materials. The hypothesis relies on improving the viscoelasticity and shear thinning behavior of platelet lysates (PL) and albumins (BSA) solutions by covalent coupling, enabling s...

Biodesign, an emerging field integrating living organisms into design solutions, offers promising approaches to global challenges. However, the interactions of designer and scientists, especially in academic settings, remain understudied. This research explores the intersection of design practices and the sciences within a higher education institut...

Multicompartmental capsules have demonstrated value in fields ranging from drug release, mimetics of artificial cells, to energy conversion and storage. However, the fabrication of devices with different compartments usually requires the use of toxic solvents, and/or the adaptation of technically demanding methods, including precision microfluidics...

The physiological functions of specific areas of the nervous system, such as the spinal cord, are directional dependent, relying on the ordered arrangement of cells and extracellular matrix. Here, an automated electrospinning method is used to make fibers with different diameters by changing the concentrations of polycaprolactone/gelatine solutions...

Background Surface topography has been shown to influence cell behavior and direct stromal cell differentiation into distinct lineages. Whereas this phenomenon has been verified in two-dimensional cultures, there is an urgent need for a thorough investigation of topography’s role within a three-dimensional (3D) environment, as it better replicates...

This study proposes a novel, versatile, and modular platform for constructing porous and heterogeneous microenvironments based on the embedding of liquefied‐based compartments in hydrogel systems. Using a bottom‐up approach, microgels carrying the necessary cargo components, including cells and microparticles, are combined with a hydrogel precursor...

Cancer is a complex pathological condition associated with substantial rates of mortality and morbidity in both humans and animals. Mammary gland tumors in intact female dogs are the most prevalent neoplasms. Surgical intervention remains the primary treatment choice. Alternative therapeutic options have emerged, with histopathological examination...

Intervertebral disc (IVD) herniation is a prevalent spinal disorder, often necessitating surgical intervention such as microdiscectomy for symptomatic relief and nerve decompression. IVDs comprise a gel‐like nucleus pulposus (NP) encased by an annulus fibrosus (AF), and their avascular nature renders them immune‐privileged. Microdiscectomy exposes...

The inclusion of hollow channels in tissue‐engineered hydrogels is crucial for mimicking the natural physiological conditions and facilitating the delivery of nutrients and oxygen to cells. Although bio‐fabrication techniques provide diverse strategies to create these channels, many require sophisticated equipment and time‐consuming protocols. Here...

Leveraging human cells as materials precursors is a promising approach for fabricating living materials with tissue-like functionalities and cellular programmability. Here we describe a set of cellular units with metabolically engineered glycoproteins that allow cells to tether together to function as macrotissue building blocks and bioeffectors. T...

One of the foremost targets in the advancement of biomaterials to engineer vascularized tissues is not only to replicate the composition of the intended tissue but also to create thicker structures incorporating a vascular network for adequate nutrients and oxygen supply. For the first time, to the best of current knowledge, a clinically relevant b...

Genome editing technologies have been key to unlock new bioengineering strategies as they enable the modification of mammalian cells genes in a fully user-programmed mode. Despite major advancements, the development...

In this review, we overview recent advancements in decoupling the cellular microenvironment from the surrounding macroenvironment in the development of biomimetic engineered tissues.

The ordered arrangement of cells and extracellular matrix facilitates the seamless transmission of electrical signals along axons in the spinal cord and peripheral nerves. Therefore, restoring tissue geometry is crucial...

In the intricate landscape of the tumor microenvironment, both cancer and stromal cells undergo rapid metabolic adaptations to support their growth. Given the relevant role of the metabolic secretome in fueling tumor progression, its unique metabolic characteristics have gained prominence as potential biomarkers and therapeutic targets. As a result...

All-aqueous immiscible systems derived from liquid-liquid phase separation of incompatible hydrophilic agents such as polymers and salts have found increasing interest in the biomedical and tissue engineering fields in the last few years. The unique characteristics of aqueous interfaces, namely their low interfacial tension and elevated permeabilit...

Humanity has long sought inspiration from nature to innovate materials and devices. As science advances, nature-inspired materials are becoming part of our lives. Animate materials, characterized by their activity, adaptability, and autonomy, emulate properties of living systems. While only biological materials fully embody these principles, artifi...

In the pursuit of advancing neural tissue regeneration, biomaterial scaffolds have emerged as promising candidates, offering potential solutions for nerve disruptions. Among these scaffolds, multichannel hydrogels, characterized by meticulously designed micrometer‐scale channels, stand out as instrumental tools for guiding axonal growth and facilit...

Protein‐based hydrogels have great potential to be used as bioinks for biofabrication‐driven tissue regeneration strategies due to their innate bioactivity. Nevertheless, their use as bioinks in conventional 3D bioprinting is impaired due to their intrinsic low viscosity. Using embedding bioprinting, a liquid bioink is printed within a support that...

Canine mammary tumors (CMTs) represent a significant health concern in dogs, with a high incidence among intact female dogs. CMTs are a promising comparative model for human breast cancer, due to sharing several pathophysiological features. Additionally, CMTs have a strong genetic correlation with their human counterpart, including the expression o...

The immune system is a pivotal player in determining tumor fate, contributing to the immunosuppressive microenvironment that supports tumor progression. Considering the emergence of biomaterials as promising platforms to mimic the tumor microenvironment, human platelet lysate(PLMA)‐based hydrogel beads are proposed as 3D platforms to recapitulate t...

Amyloid-like fibrils are garnering keen interest in biotechnology as supramolecular nanofunctional units to be used as biomimetic platforms to control cell behavior. Recent insights into fibril functionality have highlighted their importance in tissue structure, mechanical properties, and improved cell adhesion, emphasizing the need for scalable an...

Protein-based hydrogels have great potential to be used as bioinks for biofabrication-driven tissue regeneration strategies due to their innate bioactivity. Nevertheless, their use as bioinks in conventional 3D bioprinting is impaired due to their intrinsic low viscosity. Using embedding bioprinting, a liquid bioink is printed whithin a support tha...

Food smart packaging has emerged as a promising technology to address consumer concerns regarding food conservation and food safety. In this context, we report the rational design of azide-containing pyranoflavylium-based pH-sensitive dye for subsequent click chemistry conjugation toward a chitosan-modified alkyne. The chitosan-pyranoflavylium conj...

Therapeutic cells are usually administered as living agents, despite the risks of undesired cell migration and acquisition of unpredictable phenotypes. Additionally, most cell‐based therapies rely on the administration of single cells, often associated with rapid in vivo clearance. 3D cellular materials may be useful to prolong the effect of cellul...

Chronic inflammation plays a crucial role in carcinogenesis. High levels of serum prostaglandin E2 and tissue overexpression of cyclooxygenase-2 (COX-2) have been described in breast, urinary, colorectal, prostate, and lung cancers as being involved in tumor initiation, promotion, progression, angiogenesis, and immunosuppression. Non-steroidal anti...

Cardiovascular diseases are a major global cause of morbidity and mortality, and they are often characterized by cardiomyocytes dead that ultimately leads to myocardial ischemia (MI). This condition replaces functional cardiac tissue with fibrotic scar tissue compromising heart function. Injectable systems for the in situ delivery of cells or molec...

Advancing biofabrication toward manufacturing living constructs with well‐defined architectures and increasingly biologically relevant cell densities is highly desired to mimic the biofunctionality of native human tissues. The formulation of tissue‐like, cell‐dense inks for biofabrication remains, however, challenging at various levels of the biopr...

Background Surface topography has been shown to influence cell behavior and direct stromal cell differentiation into distinct lineages. Whereas this phenomenon has been verified in two-dimensional cultures, there is an urgent need for a thorough investigation of topography’s role within a three-dimensional (3D) environment, as it better replicates...

Cancer vaccination holds great promise for cancer treatment, but its effectiveness is hindered by suboptimal activation of CD8⁺ cytotoxic T lymphocytes, which are potent effectors to mediate anti-tumor immune responses. A possible solution is to switch antigen-presenting cells to present tumor antigens via the major histocompatibility complex class...

Cryogels exhibit unique shape memory with full recovery and structural stability features after multiple injections. These constructs also possess enhanced cell permeability and nutrient diffusion when compared to typical bulk hydrogels. Volumetric processing of cryogels functionalized with nanosized units has potential to widen their biomedical ap...

The stimulation of mesenchymal stromal cells (MSCs) with inflammatory molecules is often used to boost their therapeutic effect. Prolonged exposure to inflammatory molecules has been explored to improve their action because MSCs therapies seem to be improved transiently with such stimuli. However, the possibility of cyclically stimulating MSCs to r...

The coordinated migration of invasive tumor cells is a complex and dynamic mechanism driven by diverse cellular and molecular events. Unfortunately, the inherent heterogeneity within tumors raises multiple challenges in deciphering key biomarkers and novel therapeutic approaches to prevent tumor metastasis. Here, a microengineered tumor‐on‐a‐chip s...

Biomaterial-mediated bone tissue engineering (BTE) offers an alternative, interesting approach for the restoration of damaged bone tissues in postsurgery osteosarcoma treatment. This study focused on synthesizing innovative composite inks, integrating self-assembled silk fibroin (SF), tannic acids (TA), and electrospun bioactive glass nanofibers 70...

The encapsulation of single cells has emerged as a promising field in recent years, owing to its potential applications in cell‐based therapeutics, bioprinting, in vitro cell culture, high‐throughput screening, and diagnostics. Single‐cell units offer several advantages, including compatibility with standard imaging techniques, superior diffusion r...

Control over temperature in space and time is of utmost importance in many contexts, including photothermal therapies, where a good temperature monitoring and control is expected to improve their clinical outcome. One of the most promising techniques involves the use of magnetic resonance imaging, exploring the temperature change of proton relaxome...

Embedded extrusion 3D bioprinting is a rapidly emerging additive manufacturing methodology that provides a precise spatial deposition of synthetic or natural-origin low-viscosity bioinks during the extrusion printing process. Such a strategy has to date unlocked the freeform extrusion biofabrication of complex micro-to-macro-scale living architectu...

Medical adhesives are emerging as an important clinical tool as adjuvants for sutures and staples in wound closure and healing and in the achievement of hemostasis. However, clinical adhesives combining cytocompatibility, as well as strong and stable adhesion in physiological conditions, are still in demand. Herein, a mussel‐inspired strategy is ex...

Colloidal gels assembled from gelatin nanoparticles (GNPs) as particulate building blocks show strong promise to solve challenges in cell delivery and biofabrication, such as low cell survival and limited spatial retention. These gels offer evident advantages to facilitate cell encapsulation, but research on this topic is still limited, which hampe...

Hyperthermia nanotherapeutics are particularly relevant for tackling complex human cancers. The early-stage performance evaluation of innovative hyperthermic anti-cancer nanomedicines is conventionally performed in flat 2D cell cultures that do not mimic the volumetric heat transfer occurring in human tumors. Recently, advances in bioengineered 3D...

Surfaces with biological functionalities are of great interest for biomaterials, tissue engineering, biophysics, and for controlling biological processes. The layer‐by‐layer (LbL) assembly is a highly versatile methodology introduced 30 years ago, which consists of assembling complementary polyelectrolytes or biomolecules in a stepwise manner to fo...

Green technologies for the development of drug delivery systems (DDSs) are important to lower the environmental impact associated to drug manufacturing and may help decreasing risks associated to common excipients....

Cell culture-based technologies are widely utilized in various domains such as drug evaluation, toxicity assessment, vaccine and biopharmaceutical development, reproductive technology, and regenerative medicine. It has been demonstrated that pre-adsorption of extracellular matrix (ECM) proteins including collagen, laminin and fibronectin provide mo...

Background: Difficulties during the wound healing process may result in scarring, chronic wounds and sepsis. A common tissue engineering strategy to solve these problems rely on the development of 3D hydrogel scaffolds that mimic the structure, stiffness, and biological proprieties of the target tissue. One of the most effective biofabrication tech...

Conventional surgical closure techniques, such as sutures, clips, or skin closure strips, may not always provide optimal wound closure and may require invasive procedures, which can result in potential post-surgical complications. As result, there is a growing demand for innovative solutions to achieve superior wound closure and improve patient out...

Bone resident cells are constantly subjected to a range of distinct mechanical loadings, which generates a complex microenvironment. In particular, hydrostatic pressure (HP) has a key impact on modulation of cell function and fate determination. Although HP is a constant mechanical stimulus, its role in regulating the osteogenesis process within a...

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...

Designing a microenvironment that drives autonomous stromal cell differentiation toward osteogenesis while recapitulating the complexity of bone tissue remains challenging. In the current study, bone‐like microtissues are created using electrohydrodynamic atomization to form two distinct liquefied microcapsules (mCAPs): i) hydroxypyridinone (HOPO)‐...

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...

Photo‐crosslinkable platelet lysate (PL)‐based hydrogels have been proven to support human‐derived cell cultures owing to their high content of bioactive molecules, such as cytokines and growth factors. As a unique self‐maintained and biocompatible 3D scaffold, the recently reported self‐feeding hydrogels with enzyme‐empowered degradation capacity...

There is a demand to design microparticles holding surface topographies while presenting inherent bioactive cues for applications in the biomedical and biotechnological fields. Using the pool of proteins present in human‐derived platelet lysates (PL), it is reported the production of protein‐based microparticles via a simple and cost‐effective meth...

The fabrication of biological substitutes to repair, replace, or enhance tissue‐ and organ‐level functions is a long‐sought goal of tissue engineering (TE). However, the clinical translation of TE is hindered by several challenges, including the lack of suitable mechanical, chemical, and biological properties in one biomaterial, and the inability t...

Diverse applications of nanoparticles (NP) have been revolutionary for various industrial sectors worldwide. In particular, magnetic nanoparticles (MNP) have gained great interest because of their applications in specialized medical areas. This review starts with a brief overview of the magnetic behavior of MNP and a short description of their most...

Several microfabrication technologies have been used to engineer native‐like muscle tissues. However, the successful development of muscle remains a significant challenge in the tissue engineering field. Muscle tissue engineering aims to combine muscle precursor cells aligned within a highly organized 3D structure and biological factors crucial to...

The optimized physical adhesion between bees' leg hairs and pollen grains - whereby the latter's diameter aligns with the spacing between the hairs - has previously inspired the development of a biomimetic drug dressing. Combining this optimized process with the improved natural mussels' adhesion in wet environments in a dual biomimetic process, it...

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...