Sandra Camarero-Espinosa
@polymat.eu
University of The Basque Country
POLYMAT
32
Scopus Publications
3057
Scholar Citations
17
Scholar h-index
21
Scholar i10-index
Scopus Publications
- Developing double-crosslinking 3D printed hydrogels for bone tissue engineering
Giuseppe Barberi, Sandra Ramos-Díez, Calogero Fiorica, Fabio Salvatore Palumbo, Sandra Camarero-Espinosa, and Giovanna Pitarresi
Elsevier BV - 3D Niche-Inspired Scaffolds as a Stem Cell Delivery System for the Regeneration of the Osteochondral Interface
Sandra Camarero‐Espinosa, Ivo Beeren, Hong Liu, David B. Gomes, Jip Zonderland, Ana Filipa H Lourenço, Denis van Beurden, Marloes Peters, David Koper, Pieter Emans,et al.
Wiley
AbstractThe regeneration of the osteochondral unit represents a challenge due to the distinct cartilage and bone phases. Current strategies focus on the development of multiphasic scaffolds that recapitulate features of this complex unit and promote the differentiation of implanted bone‐marrow derived stem cells (BMSCs). In doing so, challenges remain from the loss of stemness during in vitro expansion of the cells and the low control over stem cell activity at the interface with scaffolds in vitro and in vivo. Here, this work scaffolds inspired by the bone marrow niche that can recapitulate the natural healing process after injury. The construct comprises an internal depot of quiescent BMSCs, mimicking the bone marrow cavity, and an electrospun (ESP) capsule that “activates” the cells to migrate into an outer “differentiation‐inducing” 3D printed unit functionalized with TGF‐β and BMP‐2 peptides. In vitro, niche‐inspired scaffolds retained a depot of nonproliferative cells capable of migrating and proliferating through the ESP capsule. Invasion of the 3D printed cavity results in location‐specific cell differentiation, mineralization, secretion of alkaline phosphatase (ALP) and glycosaminoglycans (GAGs), and genetic upregulation of collagen II and collagen I. In vivo, niche‐inspired scaffolds are biocompatible, promoted tissue formation in rat subcutaneous models, and regeneration of the osteochondral unit in rabbit models. - A Proteomic Approach to Determine Stem Cell Skeletal Differentiation Signature on Additive Manufactured Scaffolds
Clarissa Tomasina, Ronny Mohren, Sandra Camarero‐Espinosa, Berta Cillero‐Pastor, and Lorenzo Moroni
Wiley
Understanding how porous biomaterials interact with cells at their surface and how they either promote or inhibit cellular processes has presented several challenges. Additive manufacturing enables the fabrication of scaffolds with distinct compositions and designs for different tissue engineering applications. To evaluate the in vitro performance of multiple printed materials, biochemical assays can be limiting in providing valuable insight and key information to select the best tissue destination. Omics technologies like proteomics are crucial for studying important cellular events and gathering valuable information about cellular processes and mechanisms. However, only few studies focus on proteomics to decipher cell–material interactions and cell differentiation on additive manufactured scaffolds. Here, scaffolds were fabricated using three polymers (polycaprolactone (PCL), poly(ethylene oxide)–poly(butylene terephthalate) (PEOT/PBT), and polylactic acid (PLA)) through additive manufacturing. Their chondrogenic and osteogenic potential were characterized and compared using human bone marrow‐derived mesenchymal stem cells (hBMSCs) through proteomics analysis. The 3D scaffolds were all hydrophilic and displayed Young's moduli close to those of bone or cartilage for PLA and PCL and PEOT/PBT, respectively. Biochemical assays indicated that PEOT/PBT and PLA scaffolds have a greater chondrogenic potential by higher glycosaminoglycan (GAG) and collagen deposition compared to PCL. PLA and PEOT/PBT showed to be more effective in promoting bone formation, as evidenced by higher calcium deposits detected by alizarin red staining, and higher alkaline phosphatase (ALP), especially for PLA in osteogenic medium. Proteomics data revealed the most distinct separation between conditions in chondrogenic medium, which had the highest protein identification rates. Pathway analysis showed that PCL did not induce any differentiation‐related pathways when compared to PEOT/PBT and PLA in any of the tested media conditions. Analysis of PEOT/PBT proteins showed pathways involved in chondrogenesis in all three media and pathways related to hypertrophic phenotype progression in chondrogenic medium. These data suggests that PEOT/PBT is a valuable candidate for cartilage and osteochondral applications, able to drive hBMSCs differentiation without the need of growth factors. PLA was also a valuable candidate for cartilage and bone applications by upregulating both chondrogenic and osteogenic‐related proteins in maintenance and chondrogenic media. In osteogenic and maintenance media, the upregulation of angiogenic proteins makes PLA a better candidate for bone application where vascularization is key. - A facile strategy for tuning the density of surface-grafted biomolecules for melt extrusion-based additive manufacturing applications
I. A. O. Beeren, G. Dos Santos, P. J. Dijkstra, C. Mota, J. Bauer, H. Ferreira, Rui L. Reis, N. Neves, S. Camarero-Espinosa, M. B. Baker,et al.
Springer Science and Business Media LLC
AbstractMelt extrusion-based additive manufacturing (ME-AM) is a promising technique to fabricate porous scaffolds for tissue engineering applications. However, most synthetic semicrystalline polymers do not possess the intrinsic biological activity required to control cell fate. Grafting of biomolecules on polymeric surfaces of AM scaffolds enhances the bioactivity of a construct; however, there are limited strategies available to control the surface density. Here, we report a strategy to tune the surface density of bioactive groups by blending a low molecular weight poly(ε-caprolactone)5k (PCL5k) containing orthogonally reactive azide groups with an unfunctionalized high molecular weight PCL75k at different ratios. Stable porous three-dimensional (3D) scaffolds were then fabricated using a high weight percentage (75 wt.%) of the low molecular weight PCL5k. As a proof-of-concept test, we prepared films of three different mass ratios of low and high molecular weight polymers with a thermopress and reacted with an alkynated fluorescent model compound on the surface, yielding a density of 201–561 pmol/cm2. Subsequently, a bone morphogenetic protein 2 (BMP-2)-derived peptide was grafted onto the films comprising different blend compositions, and the effect of peptide surface density on the osteogenic differentiation of human mesenchymal stromal cells (hMSCs) was assessed. After two weeks of culturing in a basic medium, cells expressed higher levels of BMP receptor II (BMPRII) on films with the conjugated peptide. In addition, we found that alkaline phosphatase activity was only significantly enhanced on films containing the highest peptide density (i.e., 561 pmol/cm2), indicating the importance of the surface density. Taken together, these results emphasize that the density of surface peptides on cell differentiation must be considered at the cell-material interface. Moreover, we have presented a viable strategy for ME-AM community that desires to tune the bulk and surface functionality via blending of (modified) polymers. Furthermore, the use of alkyne–azide “click” chemistry enables spatial control over bioconjugation of many tissue-specific moieties, making this approach a versatile strategy for tissue engineering applications. Graphic abstract - rhBMP-2 induces terminal differentiation of human bone marrow mesenchymal stromal cells only by synergizing with other signals
Neda Kathami, Carolina Moreno-Vicente, Pablo Martín, Jhonatan A. Vergara-Arce, Raquel Ruiz-Hernández, Daniela Gerovska, Ana M. Aransay, Marcos J. Araúzo-Bravo, Sandra Camarero-Espinosa, and Ander Abarrategi
Springer Science and Business Media LLC
Abstract Background Recombinant human bone morphogenetic protein 2 (rhBMP-2) and human bone marrow mesenchymal stromal cells (hBM-MSCs) have been thoroughly studied for research and translational bone regeneration purposes. rhBMP-2 induces bone formation in vivo, and hBM-MSCs are its target, bone-forming cells. In this article, we studied how rhBMP-2 drives the multilineage differentiation of hBM-MSCs both in vivo and in vitro. Methods rhBMP-2 and hBM-MSCs were tested in an in vivo subcutaneous implantation model to assess their ability to form mature bone and undergo multilineage differentiation. Then, the hBM-MSCs were treated in vitro with rhBMP-2 for short-term or long-term cell-culture periods, alone or in combination with osteogenic, adipogenic or chondrogenic media, aiming to determine the role of rhBMP-2 in these differentiation processes. Results The data indicate that hBM-MSCs respond to rhBMP-2 in the short term but fail to differentiate in long-term culture conditions; these cells overexpress the rhBMP-2 target genes DKK1, HEY-1 and SOST osteogenesis inhibitors. However, in combination with other differentiation signals, rhBMP-2 acts as a potentiator of multilineage differentiation, not only of osteogenesis but also of adipogenesis and chondrogenesis, both in vitro and in vivo. Conclusions Altogether, our data indicate that rhBMP-2 alone is unable to induce in vitro osteogenic terminal differentiation of hBM-MSCs, but synergizes with other signals to potentiate multiple differentiation phenotypes. Therefore, rhBMP-2 triggers on hBM-MSCs different specific phenotype differentiation depending on the signalling environment. - The role of plasma-induced surface chemistry on polycaprolactone nanofibers to direct chondrogenic differentiation of human mesenchymal stem cells
Mahtab Asadian, Clarissa Tomasina, Yuliia Onyshchenko, Ke Vin Chan, Mohammad Norouzi, Jip Zonderland, Sandra Camarero‐Espinosa, Rino Morent, Nathalie De Geyter, and Lorenzo Moroni
Wiley
AbstractBone marrow‐derived mesenchymal stromal cells (BMSCs) are extensively being utilized for cartilage regeneration owing to their excellent differentiation potential and availability. However, controlled differentiation of BMSCs towards cartilaginous phenotypes to heal full‐thickness cartilage defects remains challenging. This study investigates how different surface properties induced by either coating deposition or biomolecules immobilization onto nanofibers (NFs) could affect BMSCs chondro‐inductive behavior. Accordingly, electrospun poly(ε‐caprolactone) (PCL) NFs were exposed to two surface modification strategies based on medium‐pressure plasma technology. The first strategy is plasma polymerization, in which cyclopropylamine (CPA) or acrylic acid (AcAc) monomers were plasma polymerized to obtain amine‐ or carboxylic acid‐rich NFs, respectively. The second strategy uses a combination of CPA plasma polymerization and a post‐chemical technique to immobilize chondroitin sulfate (CS) onto the NFs. These modifications could affect surface roughness, hydrophilicity, and chemical composition while preserving the NFs' nano‐morphology. The results of long‐term BMSCs culture in both basic and chondrogenic media proved that the surface modifications modulated BMSCs chondrogenic differentiation. Indeed, the incorporation of polar groups by different modification strategies had a positive impact on the cell proliferation rate, production of the glycosaminoglycan matrix, and expression of extracellular matrix proteins (collagen I and collagen II). The chondro‐inductive behavior of the samples was highly dependent on the nature of the introduced polar functional groups. Among all samples, carboxylic acid‐rich NFs promoted chondrogenesis by higher expression of aggrecan, Sox9, and collagen II with downregulation of hypertrophic markers. Hence, this approach showed an intrinsic potential to have a non‐hypertrophic chondrogenic cell phenotype. - Valorization of biological waste from insect-based food industry: Assessment of chitin and chitosan potential
Neda Khatami, Pedro Guerrero, Pablo Martín, Eztizen Quintela, Viviana Ramos, Laura Saa, Aitziber L. Cortajarena, Koro de la Caba, Sandra Camarero-Espinosa, and Ander Abarrategi
Elsevier BV - Advances in Additive Manufactured Scaffolds Mimicking the Osteochondral Interface
Ivo A. O. Beeren, Pieter J. Dijkstra, Carlos Mota, Sandra Camarero‐Espinosa, Matthew B. Baker, and Lorenzo Moroni
Wiley
Architectural, compositional, and mechanical gradients are present in many interfacial tissues in the body. Yet desired for regeneration, the recreation of these complex natural gradients in porous scaffolds remains a challenging task. Additive manufacturing (AM) has been highlighted as a technology to fabricate constructs to regenerate interfacial tissues. Integration of different types of gradients, which can be physical, mechanical, and/or biochemical, shows promise to control cell fate and the regeneration process in a spatial controlled manner. One of the most studied tissue interfaces is the osteochondral unit which connects cartilage to bone. This tissue is often damaged because of trauma or ageing, leading to osteoarthritis; a degenerative disease and a major cause of disability worldwide. Therefore, in view of osteochondral (OC) regeneration, a state‐of‐the‐art overview of current approaches is presented to manufacture gradient scaffolds prepared by AM techniques. The focus is on thermoplastic, hydrogel, and hybrid scaffolds comprising gradients that induce biomimicry by their physical and biological properties. The effect of these different systems on OC tissue formation in‐vitro and in‐vivo is addressed. Finally, an outlook on current trends of dynamic materials is provided, including proposals on how these materials could improve the mimicry of scaffolds applied for OC regeneration. - Alginate-waterborne polyurethane 3D bioprinted scaffolds for articular cartilage tissue engineering
R. Olmos-Juste, G. Larrañaga-Jaurrieta, I. Larraza, S. Ramos-Diez, S. Camarero-Espinosa, N. Gabilondo, and A. Eceiza
Elsevier BV - Mimicking the Graded Wavy Structure of the Anterior Cruciate Ligament
Sandra Camarero‐Espinosa, Huipin Yuan, Pieter J. Emans, and Lorenzo Moroni
Wiley
Anterior cruciate ligament (ACL) is the connective tissue providing mechanical stability to the knee joint. ACL reconstruction upon rupture remains a clinical challenge due to the high mechanical properties required for proper functioning. ACL owes its outstanding mechanical properties to the arrangement of the ECM and to the cells with distinct phenotypes present along the length of the tissue. Tissue regeneration appears as an ideal alternative. In this study, we developed a tri-phasic fibrous scaffold that mimics the structure of collagen in the native ECM, presenting a wavy intermediate zone and two aligned uncurled extremes. The mechanical properties of the wavy scaffolds presented a toe region, characteristic of the native ACL, and an extended yield and ultimate strain as compared to traditional aligned scaffolds. The presentation of a wavy fiber arrangement affected the cell organization and the deposition of a specific ECM characteristic of fibrocartilage. Cells cultured in wavy scaffolds grew in aggregates, deposited an abundant ECM rich in fibronectin and collagen II, and expressed higher amounts of collagen II, X and tenomodulin as compared to aligned scaffolds. In-vivo implantation in rabbits showed a high cellular infiltration and the formation of an oriented ECM, as compared to traditional aligned scaffolds. This article is protected by copyright. All rights reserved. - Low molecular weight poly((D,L)-lactide-co-caprolactone) liquid inks for diluent-free DLP printing of cell culture platforms
Sandra Ramos-Díez, Garazi Larrañaga-Jaurrieta, Leire Iturriaga, Ander Abarrategi, and Sandra Camarero-Espinosa
Royal Society of Chemistry (RSC)
A library of low molecular weight biocompatible inks has been developed to be used in DLP printing. The resulting inks present low viscosity and are printable without diluents or solvents, resulting in structures with high shape fidelity. - Incorporation of strontium-containing bioactive particles into PEOT/PBT electrospun scaffolds for bone tissue regeneration
Clarissa Tomasina, Giorgia Montalbano, Sonia Fiorilli, Paulo Quadros, António Azevedo, Catarina Coelho, Chiara Vitale-Brovarone, Sandra Camarero-Espinosa, and Lorenzo Moroni
Elsevier BV - Installation of click-type functional groups enable the creation of an additive manufactured construct for the osteochondral interface
Ivo A O Beeren, Pieter J Dijkstra, Ana Filipa H Lourenço, Ravi Sinha, David B Gomes, Hong Liu, Nicole Bouvy, Matthew B Baker, Sandra Camarero-Espinosa, and Lorenzo Moroni
IOP Publishing
Abstract Melt extrusion-based additive manufacturing (AM) is often used to fabricate scaffolds for osteochondral (OC) regeneration. However, there are two shortcomings associated with this scaffold manufacturing technique for engineering of tissue interfaces: (a) most polymers used in the processing are bioinert, and (b) AM scaffolds often contain discrete (material) gradients accompanied with mechanically weak interfaces. The inability to mimic the gradual transition from cartilage to bone in OC tissue leads to poor scaffold performance and even failure. We hypothesized that introducing peptide gradients on the surface could gradually guide human mesenchymal stromal cell (hMSC) differentiation, from a chondrogenic towards on osteogenic phenotype. To work towards this goal, we initially manufactured poly(ϵ-caprolactone)-azide (PCLA) and PCL-maleimide (PCLM) scaffolds. The surface exposed click-type functional groups, with a surface concentration in the 102pmol cm−2 regime, were used to introduce bone morphogenic protein-2 or transforming growth factor-beta binding peptide sequences to drive hMSC differentiation towards osteogenic or chondrogenic phenotypes, respectively. After 3 weeks of culture in chondrogenic medium, we observed differentiation towards hypertrophic chondrogenic phenotypes with expression of characteristic markers such as collagen X. In osteogenic medium, we observed the upregulation of mineralization markers. In basic media, the chondro-peptide displayed a minor effect on chondrogenesis, whereas the osteo-peptide did not affect osteogenesis. In a subcutaneous rat model, we observed a minimal foreign body response to the constructs, indicating biocompatibility. As proof-of-concept, we finally used a novel AM technology to showcase its potential to create continuous polymer gradients (PCLA and PCLM) across scaffolds. These scaffolds did not display delamination and were mechanically stronger compared to discrete gradient scaffolds. Due to the versatility of the orthogonal chemistry applied, this approach provides a general strategy for the field; we could anchor other tissue specific cues on the clickable groups, making these gradient scaffolds interesting for multiple interfacial tissue applications. - Controlling tosylation versus chlorination during end group modification of PCL
Ivo A.O. Beeren, Pieter J. Dijkstra, Philippe Massonnet, Sandra Camarero-Espinosa, Matthew B. Baker, and Lorenzo Moroni
Elsevier BV - Recent advances and future perspectives of porous materials for biomedical applications
Maria Soledad Orellano, Oihane Sanz, Sandra Camarero-Espinosa, Ana Beloqui, and Marcelo Calderón
Future Medicine Ltd - 3D Printed Dual-Porosity Scaffolds: The Combined Effect of Stiffness and Porosity in the Modulation of Macrophage Polarization
Sandra Camarero‐Espinosa, Maria Carlos‐Oliveira, Hong Liu, João F. Mano, Nicole Bouvy, and Lorenzo Moroni
Wiley
Tissue regeneration evolves towards the biofabrication of sophisticated 3D scaffolds. However, the success of these will be contingent to their capability to integrate within the host. The control of the mechanical or topographical properties of the implant, appear as ideal methods to modulate the immune response. However, the interplay between these properties is yet not clear. We created dual-porosity scaffolds with varying mechanical and topographical features and evaluated their immunomodulatory properties in rat alveolar macrophages in vitro, and in vivo in a rat subcutaneous model. Scaffolds were fabricated via additive-manufacturing and thermally induced phase separation (TIPS) methods from two copolymers with virtually identical chemistries, but different stiffness. The introduction of porosity enabled the modulation of macrophages towards anti-inflammatory phenotypes, with secretion of IL-10 and TGF-β. Soft scaffolds (< 5 kPa) resulted in a pro-inflammatory phenotype in contrast to stiffer (> 40 kPa) scaffolds of comparable porosities supporting a pro-healing phenotype, which appeared to be related to the surface spread area of cells. In vivo, stiff scaffolds integrated, while softer scaffolds appeared encapsulated after 3 weeks of implantation, resulting on chronic inflammation after 6 weeks. Our results demonstrate the importance of evaluating the interplay between topography and stiffness of candidate scaffolds. This article is protected by copyright. All rights reserved. - Strategies to Introduce Topographical and Structural Cues in 3D-Printed Scaffolds and Implications in Tissue Regeneration
Leire Iturriaga, Kyle D. Van Gordon, Garazi Larrañaga-Jaurrieta, and Sandra Camarero‐Espinosa
Wiley
Regeneration of tissues represents a current challenge and a need to treat damage and diseased organs, and is becoming determinant to alleviate the burden of healthcare systems with the increasing age of the population. Although many strategies are being developed and some scaffolds are already reaching the market, issues of formation of well‐structured and functional tissues are still prevalent. Additive manufacturing and particularly 3D printing have emerged as ideal technologies to fabricate patient‐specific scaffolds and allow for the easy modification of multiple structural parameters. Yet, these are generally composed of smooth fibers that are not able to drive, by themselves, the formation of well‐structured tissues. The use of physical cues to modulate cellular processes such as migration, proliferation, differentiation, and matrix synthesis has been proven effective in 2D. Thus, the extrapolation of these physical cues to 3D‐printed scaffolds appears as a tempting approach to promote the formation of functional tissues and thus, many strategies are being developed to this end. Herein, an overview of developed techniques to introduce topography and porosity to 3D‐printed scaffolds and their effect on the cell response and tissue formation is provided. - Janus 3D printed dynamic scaffolds for nanovibration-driven bone regeneration
Sandra Camarero-Espinosa and Lorenzo Moroni
Springer Science and Business Media LLC
AbstractThe application of physical stimuli to cell cultures has shown potential to modulate multiple cellular functions including migration, differentiation and survival. However, the relevance of these in vitro models to future potential extrapolation in vivo depends on whether stimuli can be applied “externally”, without invasive procedures. Here, we report on the fabrication and exploitation of dynamic additive-manufactured Janus scaffolds that are activated on-command via external application of ultrasounds, resulting in a mechanical nanovibration that is transmitted to the surrounding cells. Janus scaffolds were spontaneously formed via phase-segregation of biodegradable polycaprolactone (PCL) and polylactide (PLA) blends during the manufacturing process and behave as ultrasound transducers (acoustic to mechanical) where the PLA and PCL phases represent the active and backing materials, respectively. Remote stimulation of Janus scaffolds led to enhanced cell proliferation, matrix deposition and osteogenic differentiation of seeded human bone marrow derived stromal cells (hBMSCs) via formation and activation of voltage-gated calcium ion channels. - Biomimetic scaffolds obtained by electrospinning of collagen-based materials: Strategies to hinder the protein denaturation
Giorgia Montalbano, Clarissa Tomasina, Sonia Fiorilli, Sandra Camarero-Espinosa, Chiara Vitale-Brovarone, and Lorenzo Moroni
MDPI AG
The use of biomaterials and scaffolds to boost bone regeneration is increasingly gaining interest as a complementary method to the standard surgical and pharmacological treatments in case of severe injuries and pathological conditions. In this frame, the selection of biomaterials and the accurate assessment of the manufacturing procedures are considered key factors in the design of constructs able to resemble the features of the native tissue and effectively induce specific cell responses. Accordingly, composite scaffolds based on type-I-collagen can mimic the composition of bone extracellular matrix (ECM), while electrospinning technologies can be exploited to produce nanofibrous matrices to resemble its architectural organization. However, the combination of collagen and electrospinning reported several complications due to the frequent denaturation of the protein and the variability of results according to collagen origin, concentration, and solvent. In this context, the strategies optimized in this study enabled the preparation of collagen-based electrospun scaffolds characterized by about 100 nm fibers, preserving the physico-chemical properties of the protein thanks to the use of an acetic acid-based solvent. Moreover, nanoparticles of mesoporous bioactive glasses were combined with the optimized collagen formulation, proving the successful design of composite scaffolds resembling the morphological features of bone ECM at the nanoscale. - Additive manufacturing of nanocellulose based scaffolds for tissue engineering: Beyond a reinforcement filler
Tobias Kuhnt and Sandra Camarero-Espinosa
Elsevier BV
Cellulose nanomaterials (CNMs) have attracted great attention in the last decades due to the abundance of the biopolymer, the biorenewable character and the outstanding mechanical properties they account for. These, together with their biocompatibility makes them ideal candidates for tissue engineering (TE) applications. Additive manufacturing is an ideal biofabrication approach for TE, providing rapid and reliable technologies to produce scaffolds aimed for the guidance of host or implanted cells to form functional tissues. However, the control of parameters at the nanoscale that regulate cellular functions such as proliferation and differentiation remain challenging. This review article presents the latest advances in the use of CNMs as platforms to guide cellular functions in additive manufactured scaffolds. Special attention is given to functionalization routes, methods to exploit them as topographical cues and to improve the local mechanical properties together with the resulting cell-CNM interactions. - Bioprinting: From Tissue and Organ Development to in Vitro Models
Carlos Mota, Sandra Camarero-Espinosa, Matthew B. Baker, Paul Wieringa, and Lorenzo Moroni
American Chemical Society (ACS)
Bioprinting techniques have been flourishing in the field of biofabrication with pronounced and exponential developments in the past years. Novel biomaterial inks used for the formation of bioinks have been developed, allowing the manufacturing of in vitro models and implants tested preclinically with a certain degree of success. Furthermore, incredible advances in cell biology, namely, in pluripotent stem cells, have also contributed to the latest milestones where more relevant tissues or organ-like constructs with a certain degree of functionality can already be obtained. These incredible strides have been possible with a multitude of multidisciplinary teams around the world, working to make bioprinted tissues and organs more relevant and functional. Yet, there is still a long way to go until these biofabricated constructs will be able to reach the clinics. In this review, we summarize the main bioprinting activities linking them to tissue and organ development and physiology. Most bioprinting approaches focus on mimicking fully matured tissues. Future bioprinting strategies might pursue earlier developmental stages of tissues and organs. The continuous convergence of the experts in the fields of material sciences, cell biology, engineering, and many other disciplines will gradually allow us to overcome the barriers identified on the demanding path toward manufacturing and adoption of tissue and organ replacements. - Mechanosensitive regulation of stanniocalcin-1 by zyxin and actin-myosin in human mesenchymal stromal cells
Jip Zonderland, David B. Gomes, Yves Pallada, Ivan L. Moldero, Sandra Camarero-Espinosa, and Lorenzo Moroni
Wiley
Stanniocalcin‐1 (STC1) secreted by mesenchymal stromal cells (MSCs) has anti‐inflammatory functions, reduces apoptosis, and aids in angiogenesis, both in vitro and in vivo. However, little is known about the molecular mechanisms of its regulation. Here, we show that STC1 secretion is increased only under specific cell‐stress conditions. We find that this is due to a change in actin stress fibers and actin‐myosin tension. Abolishment of stress fibers by blebbistatin and knockdown of the focal adhesion protein zyxin leads to an increase in STC1 secretion. To also study this connection in 3D, where few focal adhesions and actin stress fibers are present, STC1 expression was analyzed in 3D alginate hydrogels and 3D electrospun scaffolds. Indeed, STC1 secretion was increased in these low cellular tension 3D environments. Together, our data show that STC1 does not directly respond to cell stress, but that it is regulated through mechanotransduction. This research takes a step forward in the fundamental understanding of STC1 regulation and can have implications for cell‐based regenerative medicine, where cell survival, anti‐inflammatory factors, and angiogenesis are critical. - Editorial: Novel Composites and Multi-Material Assembly Approaches for Tissue Regeneration
Ravi Sinha, Fergal J. O'Brien, and Sandra Camarero-Espinosa
Frontiers Media SA - Additive manufactured, highly resilient, elastic, and biodegradable poly(ester)urethane scaffolds with chondroinductive properties for cartilage tissue engineering
S. Camarero-Espinosa, C. Tomasina, A. Calore, and L. Moroni
Elsevier BV
Articular cartilage was thought to be one of the first tissues to be successfully engineered. Despite the avascular and non-innervated nature of the tissue, the cells within articular cartilage – chondrocytes – account for a complex phenotype that is difficult to be maintained in vitro. The use of bone marrow–derived stromal cells (BMSCs) has emerged as a potential solution to this issue. Differentiation of BMSCs toward stable and non-hypertrophic chondrogenic phenotypes has also proved to be challenging. Moreover, hyaline cartilage presents a set of mechanical properties – relatively high Young's modulus, elasticity, and resilience – that are difficult to reproduce. Here, we report on the use of additive manufactured biodegradable poly(ester)urethane (PEU) scaffolds of two different structures (500 μm pore size and 90° or 60° deposition angle) that can support the loads applied onto the knee while being highly resilient, with a permanent deformation lower than 1% after 10 compression-relaxation cycles. Moreover, these scaffolds appear to promote BMSC differentiation, as shown by the deposition of glycosaminoglycans and collagens (in particular collagen II). At gene level, BMSCs showed an upregulation of chondrogenic markers, such as collagen II and the Sox trio, to higher or similar levels than that of traditional pellet cultures, with a collagen II/collagen I relative expression of 2–3, depending on the structure of the scaffold. Moreover, scaffolds with different pore architectures influenced the differentiation process and the final BMSC phenotype. These data suggest that additive manufactured PEU scaffolds could be good candidates for cartilage tissue regeneration in combination with microfracture interventions.
RECENT SCHOLAR PUBLICATIONS
- Introducing a 4D into static and dynamic materials for tissue regeneration
S Camarero-Espinosa
BOOK OF ABSTRACTS, 25 2025 - Advances in Additive Manufactured Scaffolds Mimicking the Osteochondral Interface
IAO Beeren, PJ Dijkstra, C Mota, S Camarero‐Espinosa, MB Baker, ...
Advanced NanoBiomed Research 4 (11), 2400059 2024 - Developing double-crosslinking 3D printed hydrogels for bone tissue engineering
G Barberi, S Ramos-Dez, C Fiorica, FS Palumbo, S Camarero-Espinosa, ...
Reactive and Functional Polymers 203, 106016 2024 - 3D Niche‐Inspired Scaffolds as a Stem Cell Delivery System for the Regeneration of the Osteochondral Interface
S Camarero‐Espinosa, I Beeren, H Liu, DB Gomes, J Zonderland, ...
Advanced Materials 36 (34), 2310258 2024 - A Proteomic Approach to Determine Stem Cell Skeletal Differentiation Signature on Additive Manufactured Scaffolds
C Tomasina, R Mohren, S Camarero‐Espinosa, B Cillero‐Pastor, ...
Small Science 4 (7), 2300316 2024 - A facile strategy for tuning the density of surface-grafted biomolecules for melt extrusion-based additive manufacturing applications
IAO Beeren, G Dos Santos, PJ Dijkstra, C Mota, J Bauer, H Ferreira, ...
Bio-design and Manufacturing 7 (3), 277-291 2024 - rhBMP-2 induces terminal differentiation of human bone marrow mesenchymal stromal cells only by synergizing with other signals
N Kathami, C Moreno-Vicente, P Martn, JA Vergara-Arce, ...
Stem Cell Research & Therapy 15 (1), 124 2024 - The role of plasma‐induced surface chemistry on polycaprolactone nanofibers to direct chondrogenic differentiation of human mesenchymal stem cells
M Asadian, C Tomasina, Y Onyshchenko, KV Chan, M Norouzi, ...
Journal of Biomedical Materials Research Part A 112 (2), 210-230 2024 - Valorization of biological waste from insect-based food industry: Assessment of chitin and chitosan potential
N Khatami, P Guerrero, P Martn, E Quintela, V Ramos, L Saa, ...
Carbohydrate polymers 324, 121529 2024 - ENHANCING CARTILAGE TISSUE FORMATION IN GELMA/ALGINATE-TYRAMINE INTERPENETRATED NETWORKS (IPNS) WITH LOW INTENSITY PULSE ULTRASOUND STIMULATION (LIPUS)
G Larraaga-Jaurrieta, A Abarrategui, S Camarero-Espinosa
Orthopaedic Proceedings 106 (SUPP_2), 78-78 2024 - CONTROLLING CELL ORGANIZATION IN WAVY ELECTROSPUN SCAFFOLDS FOR THE REGENERATION OF THE ANTERIOR CRUCIATE LIGAMENT
S Camarero-Espinosa
Orthopaedic Proceedings 106 (SUPP_2), 58-58 2024 - MULTILAYER DUAL-POROSITY 3D-PRINTED SCAFFOLDS TO RECREATE THE ANISOTROPIC MICROENVIRONMENT OF THE CARTILAGE
S Ramos-Dez, S Camarero-Espinosa
Orthopaedic Proceedings 106 (SUPP_2), 17-17 2024 - A facile strategy for tuning the density of surface-grafted biomolecules formelt extrusion-based additive manufacturing applications
IAO Beeren, G dos Santos, PJ Dijkstra, C Mota, J Bauer, H Ferreira, ...
Springer 2024 - Alginate-waterborne polyurethane 3D bioprinted scaffolds for articular cartilage tissue engineering
R Olmos-Juste, G Larraaga-Jaurrieta, I Larraza, S Ramos-Diez, ...
International Journal of Biological Macromolecules 253, 127070 2023 - Mimicking the Graded Wavy Structure of the Anterior Cruciate Ligament (Adv. Healthcare Mater. 17/2023)
S Camarero‐Espinosa, H Yuan, PJ Emans, L Moroni
Advanced Healthcare Materials 12 (17), 2370092 2023 - In Vitro and In Vivo Characterization of Composite Electrospun Scaffolds with ICOS-Fc for Osteoporotic Fractures
C Tomasina, I Corvaglia, G Montalbano, M Pagani, E Boggio, CL Gigliotti, ...
TISSUE ENGINEERING PART A 29 (13-14) 2023 - Mimicking the graded wavy structure of the anterior cruciate ligament
S Camarero‐Espinosa, H Yuan, PJ Emans, L Moroni
Advanced Healthcare Materials 12 (17), 2203023 2023 - PEOT/PBT ELECTROSPUN SCAFFOLDS TARGETING OSTEOPOROSIS
C Tomasina, G Montalbano, M Pagani, E Boggio, CL Gigliotti, C Dianzani, ...
TISSUE ENGINEERING PART A 29 (11-12), 1074-1075 2023 - Incorporation of strontium-containing bioactive particles into PEOT/PBT electrospun scaffolds for bone tissue regeneration
C Tomasina, G Montalbano, S Fiorilli, P Quadros, A Azevedo, C Coelho, ...
Biomaterials Advances 149, 213406 2023 - Low molecular weight poly ((D, L)-lactide-co-caprolactone) liquid inks for diluent-free DLP printing of cell culture platforms
S Ramos-Dez, G Larraaga-Jaurrieta, L Iturriaga, A Abarrategi, ...
Biomaterials Science 11 (15), 5163-5176 2023
MOST CITED SCHOLAR PUBLICATIONS
- Current characterization methods for cellulose nanomaterials
EJ Foster, RJ Moon, UP Agarwal, MJ Bortner, J Bras, ...
Chemical Society Reviews 2018
Citations: 1020 - Isolation of thermally stable cellulose nanocrystals by phosphoric acid hydrolysis
S Camarero Espinosa, T Kuhnt, EJ Foster, C Weder
Biomacromolecules 14 (4), 1223-1230 2013
Citations: 793 - Articular cartilage: from formation to tissue engineering
S Camarero-Espinosa, B Rothen-Rutishauser, EJ Foster, C Weder
Biomaterials science 4 (5), 734-767 2016
Citations: 364 - Bioprinting: From Tissue and Organ Development to in Vitro Models
C Mota, S Camarero-Espinosa, MB Baker, P Wieringa, L Moroni
Chemical reviews 120 (19), 10547-10607 2020
Citations: 303 - A critical review of the current knowledge regarding the biological impact of nanocellulose
C Endes, S Camarero-Espinosa, S Mueller, EJ Foster, A Petri-Fink, ...
Journal of nanobiotechnology 14, 1-14 2016
Citations: 246 - Materials for the Spine: Anatomy, Problems, and Solutions
EJF Brody A. Frost, Sandra Camarero-Espinosa
Materials 12 (2), 253 2019
Citations: 205 - Directed cell growth in multi-zonal scaffolds for cartilage tissue engineering
S Camarero-Espinosa, B Rothen-Rutishauser, C Weder, EJ Foster
Biomaterials 74, 42-52 2016
Citations: 162 - Bioprinting vasculature: materials, cells and emergent techniques
C Tomasina, T Bodet, C Mota, L Moroni, S Camarero-Espinosa
Materials 12 (17), 2701 2019
Citations: 149 - Production and Applications of Cellulose Nanomaterials
S Camaero Espinosa, T Kuhnt, C Weder, EJ Foster
Tappi Press 2013
Citations: 122 - An in vitro testing strategy towards mimicking the inhalation of high aspect ratio nanoparticles
C Endes, O Schmid, C Kinnear, S Mueller, S Camarero-Espinosa, ...
Particle and fibre toxicology 11, 1-13 2014
Citations: 114 - Janus 3D printed dynamic scaffolds for nanovibration-driven bone regeneration
S Camarero-Espinosa, L Moroni
Nature communications 12 (1), 1031 2021
Citations: 73 - Cellulose nanocrystal driven crystallization of poly (d, l‐lactide) and improvement of the thermomechanical properties
S Camarero‐Espinosa, DJ Boday, C Weder, EJ Foster
Journal of Applied Polymer Science 132 (10) 2015
Citations: 58 - Elucidating the potential biological impact of cellulose nanocrystals
S Camarero-Espinosa, C Endes, S Mueller, A Petri-Fink, ...
Fibers 4 (3), 21 2016
Citations: 57 - Tailoring biomaterial scaffolds for osteochondral repair
S Camarero-Espinosa, J Cooper-White
International Journal of Pharmaceutics 523 (2), 476-489 2017
Citations: 53 - Mechanical and shape‐memory properties of poly (mannitol sebacate)/cellulose nanocrystal nanocomposites
Sonseca, S Camarero‐Espinosa, L Peponi, C Weder, EJ Foster, ...
Journal of Polymer Science Part A: Polymer Chemistry 52 (21), 3123-3133 2014
Citations: 52 - 3D printed dual‐porosity scaffolds: the combined effect of stiffness and porosity in the modulation of macrophage polarization
S Camarero‐Espinosa, M Carlos‐Oliveira, H Liu, JF Mano, N Bouvy, ...
Advanced Healthcare Materials 11 (1), 2101415 2022
Citations: 50 - Additive manufacturing of nanocellulose based scaffolds for tissue engineering: Beyond a reinforcement filler
T Kuhnt, S Camarero-Espinosa
Carbohydrate Polymers 252, 117159 2021
Citations: 48 - Poly (caprolactone-co-trimethylenecarbonate) urethane acrylate resins for digital light processing of bioresorbable tissue engineering implants
T Kuhnt, RM Garca, S Camarero-Espinosa, A Dias, AT Ten Cate, ...
Biomaterials science 7 (12), 4984-4989 2019
Citations: 43 - Additive manufacturing of an elastic poly (ester) urethane for cartilage tissue engineering
S Camarero-Espinosa, A Calore, A Wilbers, J Harings, L Moroni
Acta biomaterialia 102, 192-204 2020
Citations: 42 - Combinatorial presentation of cartilage-inspired peptides on nanopatterned surfaces enables directed differentiation of human mesenchymal stem cells towards distinct articular
S Camarero-Espinosa, JJ Cooper-White
Biomaterials 210, 105-115 2019
Citations: 35