Rui L. Reis

University of Minho · 3B's Research Group in Biomaterials, Biodegradables and Biomimetics

Introduction: PIEZO mechanoreceptors are increasingly recognized to play critical roles in fundamental physiological processes like proprioception, touch, or tendon biomechanics. However, their gating mechanisms and downstream signaling are still not completely understood, mainly due to the lack of effective tools to probe these processes. Here, we...

Stem Cell Tenogenesis | In article number 2312961, Manuela E. Gomes, Rui M. A. Domingues, and co-workers combine endogenous growth factor sequestration by molecularly imprinted nanoparticles with microcontact guidance by magnetic microfibers inside bioinspired hydrogel systems. Simultaneous control over biochemical and biophysical cues synergistic...

Extensive research has been conducted on biomimetic interfaces mimicking the complex and diverse microenvironment of cell membranes to gain insights into bioactive compound interactions and membrane biophysics modulation. The present study proposes an innovative approach that combines five prospective label‐free methodologies (derivative spectrosco...

The integration of basalt-fiber-reinforced polymer (BFRP) rebars into concrete design standards still remains unrealized due to limited knowledge on the performance of the rebars in concrete, particularly in terms of bond durability in harsh conditions. In this work, we investigated the bond durability characteristics of BFRP rebars in fiber-reinfo...

Block copolymer (BCP) self‐assembly has emerged as a feasible method for large‐scale fabrication with remarkable precision – features that are not common for most of the nanofabrication techniques. In this review, recent advancements in the molecular design of BCP along with state‐of‐the‐art processing methodologies based on microphase separation a...

Magnesium-based materials show great potential for producing biodegradable stents, but their high corrosion rates are a roadblock.This study investigates whether ultrasound melt treatment can change the corrosion response of an extruded AZ91D-1.0%Ca (wt.%) in Earle's Balanced Salt Solution by tailoring the intermetallics' morphology in the as-extru...

Anisotropy is an important cue for neural organization during morphogenesis and healing, contributing to the mechanical and functional properties of neural tissues. The ability to replicate such anisotropy in vitro holds great promise for the development of effective regeneration strategies. In this work, interfacial polyelectrolyte complexation (I...

Surface topographies of cell culture substrates can be used to generate in vitro cell culture environments similar to the in vivo cell niches. In vivo, the physical properties of the extracellular matrix (ECM), such as its topography, provide physical cues that play an important role in modulating cell function. Mimicking these properties remains a...

Adoptive cell therapy in solid tumors, such as melanoma, is impaired, but little is known about the role that the fibroblasts present in the tumor microenvironment could exert. However, the mechanism at play is not well understood, partly due to the lack of relevant pre-clinical models. Three-dimensional culture and microfluidic chips are used to r...

Collagen is a ubiquitous protein present in the extracellular matrix of all major metazoan animals, with approximately 28 different human collagen types described in the literature, each with unique physicochemical properties. Collagens found broad application in the cosmeceutical, pharmaceutical, and biomedical fields and can be isolated from envi...

Inflammatory diseases are the focus of several clinical studies, due to limitations and serious side effects of available therapies. Plant-based drugs (e.g., salicylic acid, morphine) have become landmarks in the pharmaceutical field. Therefore, we investigated the immunomodulatory effects of flowers, leaves, and roots from Echinacea purpurea. Etha...

Organ-on-a-chip devices have become a viable option for investigating critical physiological events and responses; this technology has matured substantially, and many systems have been reported for disease modeling or drug screening over the last decade. Despite the wide acceptance in the academic community, their adoption by clinical end-users is...

Background T cell priming has been shown to be a powerful immunotherapeutic approach for cancer treatment in terms of efficacy and relatively weak side effects. Systems that optimize the stimulation of T cells to improve therapeutic efficacy are therefore in constant demand. A way to achieve this is through artificial antigen presenting cells that...

Integrin-binding biomaterials have been extensively evaluated for their capacity to enable de novo formation of capillary-like structures/vessels, ultimately supporting neovascularization in vivo. Yet, the role of integrins as vascular initiators in engineered materials is still not well understood. Here, we show that αvβ3 integrin-specific 3D matr...

Growth factors (GFs) are a crucial element for tissue regeneration, but their exogenous administration has proven expensive and ineffective. Biomaterial approaches inspired by the extracellular matrix have attempted to sequester GFs, thus regulating their activity and presentation to cell receptors. Our previous work first demonstrated that molecul...

This book offers a comprehensive overview of the development and application of microfluidics and biosensors in cancer research, in particular, their applications in cancer modeling and theranostics. Over the last decades, considerable effort has been made to develop new technologies to improve the diagnosis and treatment of cancer. Microfluidics h...

The tumor microenvironment (TME) is like the Referee of a soccer match who has constant eyes on the activity of all players, such as cells, acellular stroma components, and signaling molecules for the successful completion of the game, that is, tumorigenesis. The cooperation among all the “team members” determines the characteristics of tumor, such...

Orthopedic injuries are among the common health issues, and regenerative strategies are needed in the clinics [1,2]. In the last few decades, there have been critical advances in the engineering of scaffolds, and tissue engineering. Together will cells, scaffolds play a critical role in the regeneration of tissues. Therefore, scaffolds have been de...

E. purpurea formulations, recognized as safe by the World Health Organization, have been traditionally used in the treatment of inflammatory diseases. Therefore, we investigate the anti-inflammatory capacity of E. purpurea dichloromethanolic (DE) and ethanolic extracts (EE) obtained from flowers (F) and roots (R), prepared in an Accelerated Solvent...

An important hallmark in cancer research is the discovery of suitable features capable to reliably predict tumor invasiveness, and consequently, their metastatic potential at an early stage. Current methods are based on molecular biomarker screening and imaging that may not reveal the altered properties of tumor cells, being also labor-intensive an...

Novel approaches to treat diabetes can include cell encapsulationand transplantation in order to mitigate graft rejection and restorephysiological insulin secretion and normoglycemia [1]. In thiswork, a surface engineering approach was used to modify theplasma membrane of MIN-6 cells using a Mal-PEG-Lipid. TheMal-PEG-Lipid provides an anchorage sit...

Meniscus tissue is a fibrocartilaginous tissue that has a crucial role in knee function and homeostasis including the protection of articular cartilage. Meniscus injuries are among the most frequent orthopedic injuries and can be associated with early-stage degenerative process in the knee, if not properly clinically managed and treated. To address...

Extracellular matrix (ECM)-based bioinks have been steadily gaining interest in the field of bioprinting to develop biologically relevant and functional tissue constructs. Herein, we propose the use of supercritical carbon dioxide (scCO2) technology to extract the ECM components of cell-sheets that have shown promising results in creating accurate...

Extracellular vesicles (EVs) are small lipidic particles packed with proteins, DNA, messenger RNA and microRNAs of their cell of origin that act as critical players in cell-cell communication. These vesicles have been identified as pivotal mediators in cancer progression and the formation of metastatic niches. Hence, their isolation and analysis fr...

Purpose This study aimed to systematically analyze the postoperative clinical, functional, and imaging outcomes, complications, reoperations, and failures following patellofemoral cartilage restoration surgery. Methods This review was conducted according to the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISM...

This study investigated the osteogenic performance of new brushite cements obtained from Li⁺-doped β-tricalcium phosphate as a promising strategy for bone regeneration. Lithium (Li⁺) is a promising trace element to encourage the migration and proliferation of adipose-derived stem cells (hASCs) and the osteogenic differentiation-related gene express...

Meniscus is one of the most injured tissues in orthopedics that require surgical care. Saving the meniscus is the initial intention, and repairing it with sutures is not always feasible. If the suturing of the meniscus is not possible, substitution of the meniscus with scaffolds is prefered considering the indications and contra-indications [1, 2]....

Solid-state optics has been the pillar of modern digital age. Integrating soft hydrogel materials with micro/nanooptics could expand the horizons of photonics for bioengineering. Here, wet-spun multilayer hydrogel fibers are engineered through ionic-crosslinked natural polysaccharides that serve as multifunctional platforms. The resulting flexible...

We describe the antithrombotic properties of nanopatterned coatings created by self-assembly of poly(styrene-block-2-vinylpyridine) (PS-b-P2VP) with different molecular weights. By changing the assembly conditions, we obtained nanopatterns that differ by their morphology (size and shape of the nanopattern) and chemistry. The surface exposition of P...

Introduction Although growth factors (GF) have a very promising therapeutic potential, their exogenous administration has proven costly and ineffective. Recent extracellular matrix (ECM)-inspired biomaterial approaches have sought to sequester labile therapeutic molecules, thus regulating their activity and presentation via heparin, aptamers or ot...

The creation of microphysiological systems like tissue and organ-on-chip for in vitro modeling of human physiology and diseases is gathering increasing interest. However, the platforms used to build these systems have limitations concerning implementation, automation, and cost-effectiveness. Moreover, their typical plastic-based housing materials a...

The bone is a complex and dynamic structure subjected to constant stress and remodeling. Due to the worldwide incidence of bone disorders, tissue scaffolds and engineered bone tissues have emerged as solutions for bone grafting, which require sophisticated scaffolding architectures while keeping high mechanical performance. However, the conjugation...

The generation of invasive fluctuating protrusions is a distinctive feature of tumor dissemination. During the invasion, individual cancer cells modulate the morphodynamics of protrusions to optimize their migration efficiency. However, it remains unclear how protrusion fluctuations govern the invasion of more complex multi-cellular structures, suc...

The application of additive manufacturing in the biomedical field has become a hot topic in the last decade owing to its potential to provide personalized solutions for patients. Different bioinks have been designed trying to obtain a unique concoction that addresses all the needs for tissue engineering and drug delivery purposes, among others. Des...

Natural deep eutectic systems (NADES), which have applications as solvents for both engineering and life sciences, are mainly composed of sugars, aminoacids or organic acids. In this work NADES composed by glucose, urea and proline (G:U:P in a molar ratio of 1:1:1) and proline and glucose (P:G 5:3) were prepared and added in different mass fraction...

Decades of research in orthopaedics has culminated in the quest for formidable yet resorbable biomaterials using bioactive materials. Brushite cements most salient features embrace high biocompatibility, bioresorbability, osteoconductivity, self-setting characteristics, handling, and injectability properties. Such type of materials is also effectiv...

Breast cancer is one of the leading causes of mortality worldwide being the most common cancer among women. Despite the significant progress obtained during the past years in the understanding of breast cancer pathophysiology, women continue to die from it. Novel tools and technologies are needed to develop better diagnostic and therapeutic approac...

The most remarkable attractiveness of tissue engineering technology relies on its capability of regenerating patients’ tissues and organs by using their own cells, minimizing the shortage of donor organs, and eliminating all the problems related to transplanted organs and their immune rejection. Traditionally, a suitable biomaterial is selected to...

With the worldwide increase of fisheries, fish wastes have had a similar increase, alternatively they can be seen as a source of novel substances for the improvement of society’s wellbeing. Elasmobranchs are a subclass fished in high amounts, with some species being mainly bycatch. They possess an endoskeleton composed mainly by cartilage, from whi...

Understanding the pathogenesis of viral infection is of paramount importance for the development of better therapies. In the particular case of COVID-19, the mechanism of infection is highly complex and involves a critical cascade of events, which can lead to the death of the patient. Intense research is currently being performed to gain mechanisti...

Current diagnostics present challenges that are imposed by increased life expectancy in the worldwide population. These challenges are related, not only to satisfy the need for higher performance of diagnostic tests, but also to the capacity of creating point‐of‐care, wearable, multiplexing and implantable diagnostic platforms that will allow early...

Musculoskeletal interfaces are naturally hypoxic. An understanding of key interactions occurring between different cell populations and their environment is critical for native tissue recapitulation. Here, an enthesis coculture model (preosteoblasts and tendon cells) was used to understand the influence of hypoxia (5% O2 ) and osteogenic medium (OM...

Even after the revolution of rheumatoid arthritis (RA) treatment with biologic agents, this debilitating disease remains a major clinical problem. The outstanding outcomes of the systemic administration of antibodies (Abs) are narrowed by the risk of serious side effects and limited efficacy due to their short half‐life. Interleukin‐23 (IL‐23) is a...

CD44 and the receptor for hyaluronic acid-mediated motility (RHAMM) are the main hyaluronan (HA) receptors. They are commonly overexpressed in different cancers activating signaling pathways related to tumor progression, metastasis and chemoresistance. Besides their involvement in signal transduction via interaction with HA, currently, there is a l...

The present work reports on a 3D model of the tumor microenvironment that contains hyaluronic acid (HA) and alginate, and demonstrates the utility of this model to study the effect of HA size on the crosstalk between cancer cells and mesenchymal stem cells (MSCs). The system incorporates a core that contains HA of specific size (i.e. 6.4, 741 or 15...

Rheumatoid arthritis is a rheumatic disease for which a healing treatment does not presently exist. Silk fibroin has been extensively studied for use in drug delivery systems due to its uniqueness, versatility and strong clinical track record in medicine. However, in general, natural polymeric materials are not mechanically stable enough, and have...

Inducing thermal gradients in two injected fluid systems results in the temporal formation of mixing conductive streams. If preserved through sol-gel transition, this mechanism can be used to drive and pat- tern non-living and living entities in mixed hydrogels. Interfaces are vital in nature, where gradients of non-living and living entities build...

Tendinopathies represent half of all musculoskeletal injuries worldwide. Inflammatory events contribute to both tendon healing and to tendinopathy conditions but the cellular triggers leading to one or the other are unknown. In previous studies, we showed that magnetic field actuation modulates human tendon cells (hTDCs) behavior in pro-inflammator...

The combination of marine origin biopolymers for tissue engineering (TE) applications is of high interest, due to their similarities with the proteins and polysaccharides present in the extracellular matrix of different human tissues. This manuscript reports on innovative collagen-chitosan-fucoidan cryogels formed by the simultaneous blending of th...

Marine polysaccharides are receiving wide attention not only from scientists but also from engineering and medical staff, given several properties that are being reported for this class of biopolymers, and also based on the reputation gained by the terrestrial representatives. The marine environment is a source yet to be untapped, with several appr...

This chapter focuses on the fibril forming collagens type I, II, III; collagen type V and the basement membrane collagen type IV, given either their abundance, relevance to regeneration processes and possibility to purify those collagens from marine organisms. Fishes are certainly the most investigated source for the extraction of collagen, gelatin...

The tumor microenvironment (TME), in particular the extracellular matrix (ECM), has been increasingly linked to the tumor aggressiveness and invasion. The dynamic interplay between cells and ECM regulates the normal function of tissues, modulating the cellular behavior and activating signaling events, mainly is triggered by the well-structured and...

Electro-responsive controlled drug delivery has been receiving an increasing interest as one of the on-demand drug delivery systems, aiming the improvement of the therapeutics efficacy by controlling the amount of drug release at a specific time and target site. Herein, we report a simple method to develop an electro-responsive controlled drug deli...

This study proposes a green and innovative methodology for the exploitation of natural polymers, namely chitin, by using solvents with reduced toxicity for the creation of porous structures with the potential to be used in the biomedical field. Chitin is a promising biopolymer for the design of biodegradable constructs, and encouraging developments...

Bone is a dynamic tissue with an amazing but yet limited capacity of self-healing. Bone is the second most transplanted tissue in the world and there is a huge need for bone grafts and substitutes which lead to a decrease in bone banks donors. In this study, we developed three-dimensional scaffolds based on Ti6Al4V, ZrO2 and PEEK targeting bone tis...

Spinal fusion (SF) surgery relies on medical hardware such as screws, cages and rods, complemented by bone graft or substitute, to stabilize the interventioned spine and achieve adequate bone ingrowth. SF is technically demanding, lengthy and expensive. Advances in material science and processing technologies, proposed herein, allowed the developme...

Background: The specialized dermal papilla (DP) cells and the tyrosinase-active melanocytes are central players in hair growth and pigmentation, respectively. In the hair follicle (HF), oxygen levels average about 5%O2 (physoxia) and are intimately coupled with the production of reactive oxygen species (ROS), which contribute to hair growth. Consid...

The design of innovative pharmaceutical products, able to reach unexplored market niches, requires natural materials use with improved swelling and moisture properties. Herein, chitosan (CHT), a natural polymer, was combined with virgin coconut oil (VCO), a resource extracted from coconut kernels, to develop emulsion-based films for biomedical purp...

Platelet-derived products (PDPs) have gained popularity, mainly due to their high concentrations of bioactive molecules such as growth factors and cytokines, which play important roles in tissue healing and regeneration. PDPs are obtained through minimally invasive procedures and their therapeutic effect has been widely recognized. In veterinary me...

The currently used hemostatic agents are highly effective in stopping hemorrhages but have a limited role in the modulation of the wound healing environment. Herein, we propose an intrinsically bioactive hemostatic cryogel based on platelet lysate (PL) and aldehyde-functionalized cellulose nanocrystals (a-CNC). PL have attracted great attention as...

Biosensors devices have attracted the attention of many researchers across the world. They have the capability to solve a large number of analytical problems and challenges. They are future ubiquitous devices for disease diagnosis, monitoring, treatment and health management. This review presents an overview of the biosensors field, highlighting th...

Background. Exosomes are extracellular vesicles originating from the exfoliation of the cellular membrane. They are involved in cell-to-cell and cell-to-matrix signaling, exchange of bioactive molecules, tumorigenesis and metastasis, among others. To mitigate the limited understanding of exosome transfer phenomena, we developed a simplistic model t...

Cardiovascular disorders are a healthcare problem in today´s society. The clinically available synthetic vascular grafts are thrombogenic and could induce intimal hyperplasia. Rapid endothelialization and matched mechanical properties are two major requirements to be considered when designing functional vascular grafts. Herein, an electrospun tubul...

Silk has been used in several biomedical applications, including tissue engineering, drug delivery systems, biomedical implants, and diagnostic medical devices, due to its attractive intrinsic properties such as biocompatibility, controllable biodegradability, and excellent mechanical properties. In recent years, several attempts have been made to...

Gelatin capsules (GCs) with mean size between 200 and 400 nm are prepared via sonochemical method. Their size is low that the usual size for the sonochemically obtained protein capsules and depends on the preparation conditions. The nanometer size of GCs is explained by the low‐gelatin concentration and by the denaturated state of gelatin. The infl...

Injuries affecting load bearing tendon tissues are a significant clinical burden and efficient treatments are still unmet. Tackling tendon regeneration, tissue engineering strategies aim to develop functional substitutes that recreate native tendon milieu. Tendon mimetic scaffolds capable of remote magnetic responsiveness and functionalized magneti...

Hyaluronan (HA) is a critical element of the extracellular matrix (ECM). The regulated synthesis and degradation of HA modulates the ECM chemical and physical properties that, in turn, influence cellular behavior. HA triggers signaling pathways associated with the adhesion, proliferation, migration, and differentiation of cells, mediated by its int...

Diabetes mellitus type 2 (type-2 diabetes) is a metabolic disorder characterized by the increased blood glucose concentration and insulin resistance in peripheral tissues (e.g., muscles and adipose tissue). The initiation of the pathological cascade of events that lead to type-2 diabetes has been subject of debate; however, it has been commonly acc...

A body of evidence indicates that peripheral nerves have an extraordinary yet limited capacity to regenerate after an injury. Peripheral nerve injuries have confounded professionals in this field, from neuroscientists to neurologists, plastic surgeons, and the scientific community. Despite all the efforts, full functional recovery is still seldom....

Treatment for the osteochondral defects (ODs) is more challenging nowadays that needs to be addressed by developing alternative bone tissue engineering materials. Gellan gum (GG) is a widely used natural polysaccharide in the field of tissue engineering (TE) and regenerative medicine due to its versatile properties. There are many reports about the...