Manuela Estima Gomes

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

Tendinopathies are poorly understood diseases for which treatment remains challenging. Relevant in vitro models to study human tendon physiology and pathophysiology are therefore highly needed. Here we propose the automated 3D writing of tendon microphysiological systems (MPSs) embedded in a biomimetic fibrillar support platform based on cellulose...

The tooth is made up of three mineralized tissues, enamel, dentin, and cementum, which surround a non-mineralized tissue called the dental pulp. Micro-computed tomography (mCT) is an imaging technology based on X-rays that allows non-invasive visualization of objects at a microscopic scale, according to their radiopacity and in three dimensions (3D...

Tendon mimetic scaffolds that recreate the tendon hierarchical structure and niche have increasing potential to fully restore tendon functionality. However, most scaffolds lack biofunctionality to boost the tenogenic differentiation of stem cells. In this study, we assessed the role of platelet-derived extracellular vesicles (EVs) in stem cells' te...

The persistence of inflammatory mediators in tissue niches significantly impacts regenerative outcomes and contributes to chronic diseases. Interleukin-4 (IL4) boosts pro-healing phenotypes in macrophages (Mφ) and triggers the activation of signal transducer and activator of transcription 6 (STAT6). Since the IL4/STAT6 pathway reduces Mφ responsive...

Magnetic Systems for Regenerative Medicine The magnetic manipulation of biomaterials and living cells can be leveraged to widen the available design space of bioengineered systems. In this Special Issue, organized by Rui M. A. Domingues and Manuela E. Gomes, invited experts demonstrate how these concepts are being explored in the fields of regenera...

The advancement of tissue engineering strategies has opened up new therapeutic avenues in the regeneration of many musculoskeletal tissues and cell niches. The burst of research in nanotechnology associated to tissue engineering brings inputs for the precise control of cells and cellular environments, that can play an important role in the developm...

Recreating the extracellular matrix organization and cellular patterns of anisotropic tissues in bioengineered constructs remains a significant biofabrication challenge. Magnetically‐assisted 3D bioprinting strategies can be exploited to fabricate biomimetic scaffolding systems, but they fail to provide control over the distribution of magnetic mat...

The enthesis is an extremely specific region, localized at the tendon–bone interface (TBI) and made of a hybrid connection of fibrocartilage with minerals. The direct type of enthesis tissue is commonly subjected to full laceration, due to the stiffness gradient between the soft tissues and hard bone, and this often reoccurs after surgical reconstr...

Hybrid nanoarchitectures such as magnetic polymeric micelles (MPMs) are among the most promising nanotechnology-enabled materials for biomedical applications combining the benefits of polymeric micelles and magnetic nanoparticles within a single bioinstructive system. MPMs are formed by the self-assembly of polymer amphiphiles above the critical mi...

The combined effect of surface topography and substrate rigidity in stem cell cultures is still under‐investigated, especially when biodegradable polymers are used. Herein, we assessed human bone marrow stem cell response on aliphatic polyester substrates as a function of anisotropic grooved topography and rigidity (7 and 12 kPa). Planar tissue cul...

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...

Bioengineered human skeletal muscle tissues have emerged in the last years as new in vitro systems for disease modeling. These bioartificial muscles are classically fabricated by encapsulating human myogenic precursor cells in a hydrogel scaffold that resembles the extracellular matrix. However, most of these hydrogels are derived from xenogenic so...

Tendon tissues are characterized by highly anisotropic physical properties that are responsible for their biomechanical performance and biological organization. The concept of magnetically-assisted 3D bioprinting with magnetic hydrogel bioinks can be exploited to fabricate anisotropic scaffolding materials that resemble the architecture of tendinou...

Growth factors (GFs) are a key component of tissue engineering, but their exogenous administration has proven costly and ineffective. Extracellular matrix-inspired biomaterial approaches have sought to sequester these molecules, regulating their activity and presentation to cell receptors. Our previous work has shown that molecularly imprinted nano...

Tendon tissues have highly-anisotropic physical properties that are responsible for its biomechanical performance and biological organization. The recreation of its 3D extracellular matrix (ECM) and cellular patterns in bioengineered constructs remains challenging. The concept of magnetically-assisted 3D bioprinting with magnetic hydrogel bioinks c...

Bone is a vascularized organic-inorganic composite tissue that shows a heavily-mineralized extracellular matrix (ECM) on the nanoscale. Herein, the nucleation of calcium phosphates during the biomineralization process was mimicked using negatively-charged cellulose nanocrystals (CNCs). These mineralized-CNCs were combined with platelet lysate to pr...

Clinically relevant in vitro models of human tissue's health and disease are urgently needed for a better understanding of biological mechanisms essential for the development of novel therapies. Herein, the physiological (healthy) and pathological (disease) tendon states are bioengineered by coupling the biological signaling of platelet lysate comp...

Tendinopathy is a multi-faceted pathology characterized by alterations in tendon microstructure, cellularity and collagen composition. Challenged by the possibility of regenerating pathological or ruptured tendons, the healing mechanisms of this tissue have been widely researched over the past decades. However, so far, most of the cellular players...

Extracellular vesicles (EVs) have emerged as cell-free nanotherapeutic agents for the potential treatment of multiple diseases and for tissue engineering and regenerative medicine strategies. Nevertheless, the field has typically relied on EVs derived from stem cells, the production of which in high quantities and high reproducibility is still unde...

Tendon injuries represent over 30–50% of musculoskeletal disorders worldwide, yet the available therapies do not provide complete tendon repair/regeneration and full functionality restoring. Extracellular vesicles (EVs), membrane-enclosed nanoparticles, have emerged as the next breakthrough in tissue engineering and regenerative medicine to promote...

The heterogeneity of the hierarchical tissues requires designing multipart engineered constructs as suitable tissue replacements. Herein, we propose the incorporation of platelet lysate (PL) within electrospun fiber core aiming the fabrication of functionally graded 3D scaffolds for heterotypic tissues regeneration, such as tendon-to-bone interface...

Dental pulp tissue engineering (TE) endeavors to regenerate dentin/pulp complex by combining a suitable supporting matrix, stem cells, and biochemical stimuli. Such procedures foresee a matrix that can be easily introduced into the root canal system (RCS) and tightly adhere to dentin walls to assure the dentin surface’s proper colonization with pro...

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...

Molecular imprinting (MI) has been explored as an increasingly viable tool for molecular recognition in various fields. However, imprinting of biologically relevant molecules like proteins is severely hampered by several problems. Inspired by natural antibodies, the use of epitopes as imprinting templates has been explored to circumvent those limit...

Native tendon tissues are characterized by highly-anisotropic physical properties that are responsible for its biomechanical performance and biological organization. Hydrogels have been widely proposed as scaffolding materials, but its typical structure consisting on randomly-oriented polymeric networks results in isotropic properties different fro...

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...

Tendon and ligament (T/L) engineering strategies towards clinical practice have been challenged by a paucity of understanding in the identification and still poorly described characterization of cellular niches. Prospecting how resident cell populations behave in vitro, and how cryopreservation may influence T/ L-promoting factors, can provide insi...

Platelet lysates (PL) contain a selection of proteins and growth factors (GFs) that are known to mediate cell activity. Many of these biomolecules have been identified as chemoattractants with the capacity to induce cell migration. In order to effectively deliver and retain these biomolecules to the site of injury, a scaffold containing PL could be...

Matrix stiffness is a crucial regulator of cell fate in both in vitro and in vivo setting. Although studies with non-degradable polymers have contributed to our understanding of the influence of rigidity on cell response, very little work has been conducted with biodegradable polymers that constitute the building blocks of implantable devices. Here...

This study aimed to compare the efficacy of XP-endo Finisher R and IrriSafe, with a solvent mixture of Methyl ethyl ketone/Tetrachloroethylene (MEK/TCE), in the removal of root filling residues. Twenty-four human mandibular incisors were pair-matched by micro-computed tomography according to volume and aspect ratio. After retreatment, specimens wer...

Cell sheet technology and magnetic based tissue engineering hold the potential to become instrumental in developing magnetically responsive living tissues analogues that can be potentially used both for modelling and therapeutical purposes. Cell sheet constructions more closely recreate physiological niches, through the preservation of contiguous c...

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...

Metallic implants are widely used in diverse clinical applications to aid in recovery from lesions or to replace native hard tissues. However, the lack of integration of metallic surfaces with soft tissue interfaces causes the occurrence of biomaterial-associated infections, which can trigger a complicated inflammatory response and, ultimately, imp...

Growth factors (GFs) are biomolecules with potent biological effects but inherent limitations hinder their potential as therapeutic agents and cell culture supplements in tissue engineering and regenerative medicine (TERM). Bio-materials that sequester endogenous GFs by affinity binding might circumvent such limitations and thus are being increasin...

In recent years, the inputs from magnetically assisted strategies have been contributing to the development of more sensitive screening methods and precise means of diagnosis to overcome existing and emerging treatment challenges. The features of magnetic materials enabling in vivo traceability, specific targeting and space- and time-controlled del...

Most tissues of the human body are characterized by highly anisotropic physical properties and biological organization. Hydrogels have been proposed as scaffolding materials to construct artificial tissues due to their water-rich composition, biocompatibility, and tunable properties. However, unmodified hydrogels are typically composed of randomly...

In the field of tissue engineering and regenerative medicine, hydrogels are used as biomaterials to support cell attachment and promote tissue regeneration due to their unique biomimetic characteristics. The use of natural-origin materials significantly influenced the origin and progress of the field due to their ability to mimic the native tissues...

Osteoporosis is a metabolic disorder characterized by a loss of bone mass and structure and increasing the risk of fragility fractures, mostly among postmenopausal women. Sheep is a recognized large animal model for osteoporosis research. An experimental group of ewes (3-4 years old) was subjected to ovariectomy (OVX) and weekly glucocorticoid (GC)...

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...

Although it has been repeatedly indicated the importance to develop implantable devices and cell culture substrates with tissue-specific rigidity, current commercially available products, in particular cell culture substrates, have rigidity values well above most tissues in the body. Herein, six resorbable polyester films were fabricated using comp...

Growth factors (GFs) are proteins secreted by cells that regulate a variety of biological processes. Although they have long been proposed as potent therapeutic agents, their administration in a soluble form has proven costly and ineffective due to their short half‐lives in biological environments. Biomaterial‐based approaches are increasingly soug...

Towards the repair of damaged tissues, numerous scaffolds have been fabricated to recreate the complex extracellular matrix (ECM) environment to support desired cell behaviors; however, it is often challenging to design scaffolds with the requisite cell-anchorage sites, mechanical stability, and tailorable physicochemical properties necessary for m...

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...

Background: This work aimed to evaluate the efficacy of sonic agitation of a binary mixture of solvents (methyl ethyl ketone/tetrachloroethylene) on filling remnants removal and compare the effects of solvent agitation with the enlargement to the next instrument size. Methods: Twenty-four mandibular incisors were prepared with ProTaper Next (X1,...

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...

Inflammation is part of the natural healing response, but it has been simultaneously associated with tendon disorders, as persistent inflammatory events contribute to physiological changes that compromise tendon functions. The cellular interactions within a niche are extremely important for healing. While human tendon cells (hTDCs) are responsible...

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...

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...

Cellulose nanocrystals can bind different patterns of platelet lysate-derived protein in a surface sulfation dependent manner. The potential to direct stem cell fate by solid-phase presentation of defined protein coronas is demonstrated.

The poor healing capacity of tendons is known to worsen in the elderly. During tendon aging and degeneration, endogenous human tendon stem/progenitor cells (hTSPCs) experience profound pathological changes. Here, we explored a rejuvenation strategy for hTSPCs derived from aged/degenerated Achilles tendons (A-TSPCs) by providing three-dimensional (3...

The use of naturally occurring materials as scaffolds to support cell growth and proliferation significantly impacted the origin and progress of tissue engineering and regenerative medicine. However, the majority of these materials failed to provide adequate cues to guide cell differentiation toward the formation of new tissues. Over the past decad...

Maxillofacial bone defects resulting from tumor resection are a major cause of both esthetic and functional disabling. Currently, vascularized autologous bone flaps are the “gold standard” for reconstructive surgeries. The collection of the bone grafts commonly causes donor site morbidity. Moreover, despite the functional and aesthetic gain achieve...

Tendon tissues connect muscle to bone allowing the transmission of forces resulting in joint movement. Tendon injuries are prevalent in society and the impact on public health is of utmost concern. Thus, clinical options for tendon treatments are demanding, and tissue engineering aims to provide reliable and successful long-term regenerative soluti...

The innate graded structural and compositional profile of musculoskeletal tissues interfaces is disrupted and replaced by fibrotic tissue in the context of disease and degeneration. Tissue engineering strategies focused on the restoration of the transitional complexity found in those junctions present special relevance for regenerative medicine. He...

Strategies aiming at controlling and modulating inflammatory cues may offer therapeutic solutions for improving tendon regeneration. This study aims to investigate the modulatory effect of pulsed electromagnetic field (PEMF) on the inflammatory profile of human tendon‐derived cells (hTDCs) after supplementation with IL‐1β. IL‐1β was used to artific...

Engineering tissue-like scaffolds that can mimic the microstructure, architecture, topology, and mechanical properties of native tissues while offering an excellent environment for cellular growth has remained an unmet need. To address these challenges, multi-compartment composite fibers are fabricated. These fibers can be assembled through textile...

Tendon injuries constitute a significant healthcare problem with variable clinical outcomes. The complex interplay of tissue homeostasis, degeneration, repair, and regeneration makes the development of successful delivery therapeutic strategies challenging. Platelet-rich hemoderivatives, a source of supra-physiologic concentrations of human therape...

Identification of a suitable cell source and bioactive agents guiding cell differentiation towards tenogenic phenotype represents a prerequisite for advancement of cell‐based therapies for tendon repair. Human adipose‐derived stem cells (hASCs) are a promising, yet intrinsically heterogenous population with diversified differentiation capacities. I...

Herein we show the influence of the concentration of iron oxide nanoparticles (IONPs), incorporated on the food, on the silk gland and midgut morphology of Bombyx mori silkworms.

Most tissues of the human body are characterized by highly anisotropic physical properties and biological organization. Hydrogels have been proposed as the most promising scaffolding materials to construct artificial tissues due to their water-rich composition, biocompatibility and tunable properties. However, hydrogels are typically composed of ra...

Tendons are highly specialized load-bearing tissues with very limited healing capacity. Given their mechanosensitive nature, the combination of tendon mimetic scaffolds with remote mechanical actuation could synergistically contribute to fabricate improved tissue engineered alternatives for the functional regeneration of tendons. Here, hybrids of c...

Microbial infections from post-surgery or other medical-related procedure is a serious health problem. Nowadays, the research is focused on the development of new drug-free materials with antibacterial properties to prevent or minimize the risk of infections. Spider silk is known for its unique biomechanical properties allied with biocompatibility....

Three-dimensional (3D) bioprinting holds the promise to fabricate tissue and organ substitutes for regenerative medicine. However, the lack of bioactive inks to fabricate and support functional living constructs is one of the main limitations hindering the progress of this technology. In this study, a biofunctional human-based nanocomposite bioink...

Musculoskeletal diseases are increasing the prevalence of physical disability worldwide. Within the body, musculoskeletal soft and hard tissues integrate through specific multitissue transitions, allowing for body movements. Owing to their unique compositional and structural gradients, injuries challenge the na- tive interfaces and tissue regenerat...

Hyaluronic acid (HA)-based hydrogels have been widely used as cell culture substrates, adhesives and fillers for clinical therapeutics, and drug delivery vehicles, with promising results. Due to the limited mechanical properties, degradation rates, and biological activity of HA, it is important that HA be chemically modified, cross-linked or reinfo...

Tendon tissues have limited healing capacity. The high incidence of tendon injuries and unsatisfactory clinical outcomes of tendon repair have been a major driving force in the search for alternative therapies. Cellular therapies have been envisioned whereby the delivery of regeneration-competent cells may cause a shift in tendon healing from pro-f...

Tendon tissues have limited healing capacity. The incidence of tendon injuries and the unsatisfactory functional outcomes of tendon repair are driving the search for alternative therapeutic approaches envisioning tendon regeneration. Cellular therapies aim at delivering adequate, regeneration-competent cell types to the injured tendon and toward ul...