Carlos Semino - Academia.edu (original) (raw)

Papers by Carlos Semino

Journal of Visualized Experiments, Jun 13, 2018

Adult articular cartilage presents poor intrinsic capacity for regeneration, and after injury, ce... more Adult articular cartilage presents poor intrinsic capacity for regeneration, and after injury, cellular or biomaterial-based therapeutic platforms are required to assist repair promotion. Cartilage tissue engineering (CTE) aims to produce cartilage-like tissues that recreate the complex mechanical, biophysical and biological properties found in vivo. In terms of biomaterials used for CTE, threedimensional (3D) self-assembling peptide scaffolds (SAPS) are very attractive for their unique properties, such as biocompatibility, optional possibility of rationally design cell-signaling capacity, biodegradability and modulation of its biomechanical properties. The most attractive cell types currently used for CTE are autologous chondrocytes and adult stem cells. The use of chondrocytes in cell-based therapies for cartilage lesions is limited by quantity and requires an in vitro 2D expansion, which leads to cell dedifferentiation. In the present chapter, we report the development of heparin-, chondroitin sulfate-, decorin-, and poly(ε-caprolactone)-based self-assembling peptide composite scaffolds to promote re-differentiation of expanded human articular chondrocytes and induction of adipose-derived stem cells to chondrogenic commitment.

Computers in Biology and Medicine, Oct 1, 2016

Cell clustering and aggregation are fundamental processes in the development of several tissues a... more Cell clustering and aggregation are fundamental processes in the development of several tissues and the progression of many diseases. The formation of these aggregates also has a direct impact on the oxygen concentration in their surroundings due to cellular respiration and poor oxygen diffusion through clusters. In this work, we propose a mathematical model that is capable of simulating cell cluster formation in 3D cultures through combining a particle-based and a finite element approach to recreate complex experimental conditions. Cells are modelled considering cell proliferation, cell death and cell-cell mechanical interactions. Additionally, the oxygen concentration profile is calculated through finite element analysis using a reaction-diffusion model that considers cell oxygen consumption and diffusion through the extracellular matrix and the cell clusters. In our model, the local oxygen concentration in the medium determines both cell proliferation and cell death. Numerical predictions are also compared with experimental data from the literature. The simulation results indicate that our model can predict cell clustering, cluster growth and oxygen distribution in 3D cultures. We conclude that the initial cell distribution, cell death and cell proliferation dynamics determine the size and density of clusters. Moreover, these phenomena are directly affected by the oxygen transport in the 3D culture.

Biomolecules, Dec 28, 2019

Degenerative cartilage pathologies are nowadays a major problem for the world population. Factors... more Degenerative cartilage pathologies are nowadays a major problem for the world population. Factors such as age, genetics or obesity can predispose people to suffer from articular cartilage degeneration, which involves severe pain, loss of mobility and consequently, a loss of quality of life. Current strategies in medicine are focused on the partial or total replacement of affected joints, physiotherapy and analgesics that do not address the underlying pathology. In an attempt to find an alternative therapy to restore or repair articular cartilage functions, the use of bioengineered tissues is proposed. In this study we present a three-dimensional (3D) bioengineered platform combining a 3D printed polycaprolactone (PCL) macrostructure with RAD16-I, a soft nanofibrous self-assembling peptide, as a suitable microenvironment for human mesenchymal stem cells' (hMSC) proliferation and differentiation into chondrocytes. This 3D bioengineered platform allows for long-term hMSC culture resulting in chondrogenic differentiation and has mechanical properties resembling native articular cartilage. These promising results suggest that this approach could be potentially used in articular cartilage repair and regeneration.

Springer eBooks, 2021

Right after fertilization, most organisms’ early growth and development in general need to happen... more Right after fertilization, most organisms’ early growth and development in general need to happen very quickly. Why? Because most organisms are autonomous life-forms from the very beginning of their existence, like invertebrates, fishes, reptiles, amphibians, and birds. In this chapter, the main strategies for multicellular organisms to produce enough offspring that would contribute to the next generation and therefore to become fertile and procreate will be described. Most remarkable, despite of the evident diversity that exists among animal species (insects, mollusks, crustaceans, birds, reptiles, and mammals), the fundamental principles that apply during the reproductive process are very similar.

Biomedicines, Jul 29, 2022

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Gels, Aug 2, 2018

Cancer research has traditionally relied on two-dimensional (2D) cell culture, focusing mainly on... more Cancer research has traditionally relied on two-dimensional (2D) cell culture, focusing mainly on cancer cells and their abnormal genetics. However, over the past decade, tumors have been accepted as complex tissues rather than a homogenous mass of proliferating cells. Consequently, cancer cells' behavior can only be deciphered considering the contribution of the cells existing in the tumor stroma as well as its complex microenvironment. Since the tumor microenvironment plays a critical role in tumorigenesis, it is widely accepted that culturing cells in three-dimensional (3D) scaffolds, which mimic the extracellular matrix, represents a more realistic scenario. In the present work, an in vitro 3D co-culture system based on the self-assembling peptide scaffold RAD16-I (SAPS RAD16-I) was developed as a cancer model. For that, PANC-1 cells were injected into a RAD16-I peptide scaffold containing fibroblasts, resulting in a 3D system where cancer cells were localized in a defined area within a stromal cells matrix. With this system, we were able to study the effect of three well-known pharmaceutical drugs (Gemcitabine, 5-Fluorouracil (5-FU), and 4-Methylumbelliferone (4-MU)) in a 3D context in terms of cell proliferation and survival. Moreover, we have demonstrated that the anti-cancer effect of the tested compounds can be qualitatively and quantitatively evaluated on the developed 3D co-culture system. Experimental results showed that Gemcitabine and 5-FU prevented PANC-1 cell proliferation but had a high cytotoxic effect on fibroblasts as well. 4-MU had a subtle effect on PANC-1 cells but caused high cell death on fibroblasts.

Biomolecular Engineering, Feb 1, 2007

A plasma process for the surface modification of HA powders has been developed. Acrylic acid and ... more A plasma process for the surface modification of HA powders has been developed. Acrylic acid and acrylic acid/octadiene plasma deposited films onto HA particles have demonstrated to interact with SBF allowing the calcium dissolution–precipitation mechanism. Therefore, a nanostructured composite between HA and a self-assembling peptide scaffold (RAD16-I) has been developed. The differentiation of mESC in this scaffold has been studied,

Afinidad, 2019

espanolLa investigacion en cancer se ha basado tradicio-nalmente en los cultivos celulares en 2D,... more espanolLa investigacion en cancer se ha basado tradicio-nalmente en los cultivos celulares en 2D, centran-dose mayoritariamente en las celulas cancerigenas y su genetica anomala. No obstante, los tumores son actualmente aceptados como tejidos complejos, y como tales, necesitan senales de un ambiente 3D para formar estructuras tisulares in viro. Ademas, el comportamiento de las celulas tumorales solo puede ser descifrado considerando tambien la contribucion de las celulas existentes en el estroma del tumor, asi como de su complejo microambiente. Debido a que el microambiente del tumor tiene un papel importante en la progresion del cancer, es ampliamente aceptado que cultivar las celulas en scaffolds 3D, que imitan la matriz extracelular nativa, representa un escenario mas realista. En este trabajo tenemos como objetivo desarrollar un sistema in vitro de co-cultivo 3D, que comprensa tanto celulas cancerigenas como celulas estromales. Para esto, las celulas HeLa fueron inyec-tadas en el scaffold peptidico RAD16-I, que contenia fibroblastos, resultando en un sistema 3D donde las celulas cancerigenas quedaban rodeadas por una ma-triz de celulas estromales. Con este sistema hemos sido capaces de estudiar el comportamiento de las celulas tumorales en un contexto 3D, en terminos de supervivencia, migracion y proliferacion. Ademas, hemos demostrado que el efecto anticancerigeno de diferentes farmacos (Gemcitabina, 5-Fluorouracilo y el inhibidor de ROCK Y-27632) pueden ser cualitati-vamente i cuantitativamente evaluado en el sistema de co-cultivo 3D desarrollado. EnglishCancer research has traditionally relied on 2D cell culture, focusing mainly on cancer cells and its dis-rupted genetics. However, tumors have been accept-ed as complex tissues, and as such, they need signals from a 3D environment to form tissue structures in vitro. Moreover, cancer cells behavior can only be deciphered considering the contribution of the cells existing in the tumor stroma as well as its complex microenvironment. Since the tumor microenviron-ment plays an important role in cancer progression, it is widely accepted that culturing cells in 3D scaffolds, which mimic the native extracellular matrix, rep-resents a more realistic scenario. In the present work we aim to develop an in vitro 3D co-culture system that would comprise both cancer and stromal cells. For that, HeLa cells were injected into a RAD16-I peptide scaffold containing fibroblasts, resulting in a 3D system were cancer cells were embedded within a stromal cells matrix. With this system, we were able to study cancer cells behavior in a 3D context in terms of survival, migration and proliferation. Moreover, we have demonstrated that the anti-cancer effect of different pharmaceutical drugs (Gemcitabine, 5-Flu-orouracil and the ROCK inhibitor Y-27632) can be qualitatively and quantitatively evaluated on the 3D co-culture system developed. catalaLa recerca en cancer s’ha basat tradicionalment en els cultius cel·lulars en 2D, centrant-se sobretot en les cel·lules cancerigenes i la seva genetica anomala. No obstant, els tumors son actualment acceptats com a teixits complexos, i com a tals, necessiten senyals d’un ambient 3D per a formar estructures tissulars in vit-ro. A mes, el comportament de les cel·lules tumorals nomes pot ser desxifrat considerant tambe la con-tribucio de les cel·lules existents en l’estroma del tu-mor, aixi com del seu complex microambient. Ja que el microambient del tumor juga un paper important en la progressio del cancer, es ampliament acceptat que cultivar les cel·lules en scaffolds 3D, que imiten la matriu extracel·lular nativa, representa un escenari mes realista. En aquest treball tenim com a objectiu desenvolupar un sistema in vitro de co-cultiu 3D, que comprengui tant cel·lules cancerigenes com cel·lules estromals. Per a aixo, les cel·lules HeLa varen ser in-jectades en l’scaffold peptidic RAD16-I que contenia fibroblasts, resultant en un sistema 3D on les cel·lules cancerigenes quedaven rodejades per una matriu de cel·lules estromals. Amb aquests sistema hem sigut capacos d’estudiar el comportament de les cel·lules tumorals en un context 3D, en termes de superviven-cia, migracio i proliferacio. A mes a mes, hem demos-trat que l’efecte anti-cancerigen de diferents farmacs (Gemcitabina, 5-Fluorouracil i l’inhibidor de ROCK Y-27632) por ser qualitativament i quantitativament avaluat en el sistema de co-cultiu 3D desenvolupat.

The Never-Ending Story of Life, 2021

Macromolecular Materials and Engineering, 2019

Please correct your galley proofs carefully and return them no more than four days after the page... more Please correct your galley proofs carefully and return them no more than four days after the page proofs have been received. The editors reserve the right to publish your article without your corrections if the proofs do not arrive in time. Note that the author is liable for damages arising from incorrect statements, including misprints.

Materials, 2016

Adult articular cartilage has a limited capacity for growth and regeneration and, with injury, ne... more Adult articular cartilage has a limited capacity for growth and regeneration and, with injury, new cellular or biomaterial-based therapeutic platforms are required to promote repair. Tissue engineering aims to produce cartilage-like tissues that recreate the complex mechanical and biological properties found in vivo. In this study, a unique composite scaffold was developed by infiltrating a three-dimensional (3D) woven microfiber poly (ε-caprolactone) (PCL) scaffold with the RAD16-I self-assembling nanofibers to obtain multi-scale functional and biomimetic tissue-engineered constructs. The scaffold was seeded with expanded dedifferentiated human articular chondrocytes and cultured for four weeks in control and chondrogenic growth conditions. The composite constructs were compared to control constructs obtained by culturing cells with 3D woven PCL scaffolds or RAD16-I independently. High viability and homogeneous cell distribution were observed in all three scaffolds used during the term of the culture. Moreover, gene and protein expression profiles revealed that chondrogenic markers were favored in the presence of RAD16-I peptide (PCL/RAD composite or alone) under chondrogenic induction conditions. Further, constructs displayed positive staining for toluidine blue, indicating the presence of synthesized proteoglycans. Finally, mechanical testing showed that constructs containing the PCL scaffold maintained the initial shape and viscoelastic behavior throughout the culture period, while constructs with RAD16-I scaffold alone contracted during culture time into a stiffer and compacted structure. Altogether, these results suggest that this new composite scaffold provides important mechanical requirements for a cartilage replacement, while providing a biomimetic microenvironment to re-establish the chondrogenic phenotype of human expanded articular chondrocytes.

Evaluation of the self-assembling peptide RAD16-I as a support scaffold for chondrogenic differen... more Evaluation of the self-assembling peptide RAD16-I as a support scaffold for chondrogenic differentiation using dedifferentiated bovine chondrocytes.

Biomolecules, 2022

One of the most desirable properties that biomaterials designed for tissue engineering or drug de... more One of the most desirable properties that biomaterials designed for tissue engineering or drug delivery applications should fulfill is biodegradation and resorption without toxicity. Therefore, there is an increasing interest in the development of biomaterials able to be enzymatically degraded once implanted at the injury site or once delivered to the target organ. In this paper, we demonstrate the protease sensitivity of self-assembling amphiphilic peptides, in particular, RAD16-I (AcN-RADARADARADARADA-CONH2), which contains four potential cleavage sites for trypsin. We detected that when subjected to thermal denaturation, the peptide secondary structure suffers a transition from β-sheet to random coil. We also used Matrix-Assisted Laser Desorption/Ionization-Time-Of-Flight (MALDI-TOF) to detect the proteolytic breakdown products of samples subjected to incubation with trypsin as well as atomic force microscopy (AFM) to visualize the effect of the degradation on the nanofiber scaff...

The Never-Ending Story of Life, 2021

The essential principle of life perpetuation through uninterrupted life cycles of individual orga... more The essential principle of life perpetuation through uninterrupted life cycles of individual organisms is described in detail. During this process, life flows by acquiring many forms such as the gametes formed by individuals, gamete fusion (egg fertilization), embryogenesis, growth and development, adulthood, and sexual maturation, and again, another cycle of life is initiated. Nevertheless, the key factor for this process to operate is based on the basic principle that individuals have a finite lifespan while life is propagated indefinitely.

The Never-Ending Story of Life, 2021

Epilogue: The Future of Humankind Could Depend on Unicellular Life Summary It is very clear for m... more Epilogue: The Future of Humankind Could Depend on Unicellular Life Summary It is very clear for most of us that life in our planet is becoming more and more restricted in terms of having enough resources to support everyone's subsistence. This without question could cause in the near future a massive crisis for survival. But before this would happen, we could have one or two more chances to survive. Our first option is to solve our population growth dynamics, and the second is to prepare ourselves for a long trip to other worlds, outside our solar system. Both scenarios are considered to evaluate how we can contribute to the never-ending story of life.

Journal of Visualized Experiments, Jun 13, 2018

Adult articular cartilage presents poor intrinsic capacity for regeneration, and after injury, ce... more Adult articular cartilage presents poor intrinsic capacity for regeneration, and after injury, cellular or biomaterial-based therapeutic platforms are required to assist repair promotion. Cartilage tissue engineering (CTE) aims to produce cartilage-like tissues that recreate the complex mechanical, biophysical and biological properties found in vivo. In terms of biomaterials used for CTE, threedimensional (3D) self-assembling peptide scaffolds (SAPS) are very attractive for their unique properties, such as biocompatibility, optional possibility of rationally design cell-signaling capacity, biodegradability and modulation of its biomechanical properties. The most attractive cell types currently used for CTE are autologous chondrocytes and adult stem cells. The use of chondrocytes in cell-based therapies for cartilage lesions is limited by quantity and requires an in vitro 2D expansion, which leads to cell dedifferentiation. In the present chapter, we report the development of heparin-, chondroitin sulfate-, decorin-, and poly(ε-caprolactone)-based self-assembling peptide composite scaffolds to promote re-differentiation of expanded human articular chondrocytes and induction of adipose-derived stem cells to chondrogenic commitment.

Computers in Biology and Medicine, Oct 1, 2016

Cell clustering and aggregation are fundamental processes in the development of several tissues a... more Cell clustering and aggregation are fundamental processes in the development of several tissues and the progression of many diseases. The formation of these aggregates also has a direct impact on the oxygen concentration in their surroundings due to cellular respiration and poor oxygen diffusion through clusters. In this work, we propose a mathematical model that is capable of simulating cell cluster formation in 3D cultures through combining a particle-based and a finite element approach to recreate complex experimental conditions. Cells are modelled considering cell proliferation, cell death and cell-cell mechanical interactions. Additionally, the oxygen concentration profile is calculated through finite element analysis using a reaction-diffusion model that considers cell oxygen consumption and diffusion through the extracellular matrix and the cell clusters. In our model, the local oxygen concentration in the medium determines both cell proliferation and cell death. Numerical predictions are also compared with experimental data from the literature. The simulation results indicate that our model can predict cell clustering, cluster growth and oxygen distribution in 3D cultures. We conclude that the initial cell distribution, cell death and cell proliferation dynamics determine the size and density of clusters. Moreover, these phenomena are directly affected by the oxygen transport in the 3D culture.

Biomolecules, Dec 28, 2019

Degenerative cartilage pathologies are nowadays a major problem for the world population. Factors... more Degenerative cartilage pathologies are nowadays a major problem for the world population. Factors such as age, genetics or obesity can predispose people to suffer from articular cartilage degeneration, which involves severe pain, loss of mobility and consequently, a loss of quality of life. Current strategies in medicine are focused on the partial or total replacement of affected joints, physiotherapy and analgesics that do not address the underlying pathology. In an attempt to find an alternative therapy to restore or repair articular cartilage functions, the use of bioengineered tissues is proposed. In this study we present a three-dimensional (3D) bioengineered platform combining a 3D printed polycaprolactone (PCL) macrostructure with RAD16-I, a soft nanofibrous self-assembling peptide, as a suitable microenvironment for human mesenchymal stem cells' (hMSC) proliferation and differentiation into chondrocytes. This 3D bioengineered platform allows for long-term hMSC culture resulting in chondrogenic differentiation and has mechanical properties resembling native articular cartilage. These promising results suggest that this approach could be potentially used in articular cartilage repair and regeneration.

Springer eBooks, 2021

Right after fertilization, most organisms’ early growth and development in general need to happen... more Right after fertilization, most organisms’ early growth and development in general need to happen very quickly. Why? Because most organisms are autonomous life-forms from the very beginning of their existence, like invertebrates, fishes, reptiles, amphibians, and birds. In this chapter, the main strategies for multicellular organisms to produce enough offspring that would contribute to the next generation and therefore to become fertile and procreate will be described. Most remarkable, despite of the evident diversity that exists among animal species (insects, mollusks, crustaceans, birds, reptiles, and mammals), the fundamental principles that apply during the reproductive process are very similar.

Biomedicines, Jul 29, 2022

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Gels, Aug 2, 2018

Cancer research has traditionally relied on two-dimensional (2D) cell culture, focusing mainly on... more Cancer research has traditionally relied on two-dimensional (2D) cell culture, focusing mainly on cancer cells and their abnormal genetics. However, over the past decade, tumors have been accepted as complex tissues rather than a homogenous mass of proliferating cells. Consequently, cancer cells' behavior can only be deciphered considering the contribution of the cells existing in the tumor stroma as well as its complex microenvironment. Since the tumor microenvironment plays a critical role in tumorigenesis, it is widely accepted that culturing cells in three-dimensional (3D) scaffolds, which mimic the extracellular matrix, represents a more realistic scenario. In the present work, an in vitro 3D co-culture system based on the self-assembling peptide scaffold RAD16-I (SAPS RAD16-I) was developed as a cancer model. For that, PANC-1 cells were injected into a RAD16-I peptide scaffold containing fibroblasts, resulting in a 3D system where cancer cells were localized in a defined area within a stromal cells matrix. With this system, we were able to study the effect of three well-known pharmaceutical drugs (Gemcitabine, 5-Fluorouracil (5-FU), and 4-Methylumbelliferone (4-MU)) in a 3D context in terms of cell proliferation and survival. Moreover, we have demonstrated that the anti-cancer effect of the tested compounds can be qualitatively and quantitatively evaluated on the developed 3D co-culture system. Experimental results showed that Gemcitabine and 5-FU prevented PANC-1 cell proliferation but had a high cytotoxic effect on fibroblasts as well. 4-MU had a subtle effect on PANC-1 cells but caused high cell death on fibroblasts.

Biomolecular Engineering, Feb 1, 2007

A plasma process for the surface modification of HA powders has been developed. Acrylic acid and ... more A plasma process for the surface modification of HA powders has been developed. Acrylic acid and acrylic acid/octadiene plasma deposited films onto HA particles have demonstrated to interact with SBF allowing the calcium dissolution–precipitation mechanism. Therefore, a nanostructured composite between HA and a self-assembling peptide scaffold (RAD16-I) has been developed. The differentiation of mESC in this scaffold has been studied,

Afinidad, 2019

espanolLa investigacion en cancer se ha basado tradicio-nalmente en los cultivos celulares en 2D,... more espanolLa investigacion en cancer se ha basado tradicio-nalmente en los cultivos celulares en 2D, centran-dose mayoritariamente en las celulas cancerigenas y su genetica anomala. No obstante, los tumores son actualmente aceptados como tejidos complejos, y como tales, necesitan senales de un ambiente 3D para formar estructuras tisulares in viro. Ademas, el comportamiento de las celulas tumorales solo puede ser descifrado considerando tambien la contribucion de las celulas existentes en el estroma del tumor, asi como de su complejo microambiente. Debido a que el microambiente del tumor tiene un papel importante en la progresion del cancer, es ampliamente aceptado que cultivar las celulas en scaffolds 3D, que imitan la matriz extracelular nativa, representa un escenario mas realista. En este trabajo tenemos como objetivo desarrollar un sistema in vitro de co-cultivo 3D, que comprensa tanto celulas cancerigenas como celulas estromales. Para esto, las celulas HeLa fueron inyec-tadas en el scaffold peptidico RAD16-I, que contenia fibroblastos, resultando en un sistema 3D donde las celulas cancerigenas quedaban rodeadas por una ma-triz de celulas estromales. Con este sistema hemos sido capaces de estudiar el comportamiento de las celulas tumorales en un contexto 3D, en terminos de supervivencia, migracion y proliferacion. Ademas, hemos demostrado que el efecto anticancerigeno de diferentes farmacos (Gemcitabina, 5-Fluorouracilo y el inhibidor de ROCK Y-27632) pueden ser cualitati-vamente i cuantitativamente evaluado en el sistema de co-cultivo 3D desarrollado. EnglishCancer research has traditionally relied on 2D cell culture, focusing mainly on cancer cells and its dis-rupted genetics. However, tumors have been accept-ed as complex tissues, and as such, they need signals from a 3D environment to form tissue structures in vitro. Moreover, cancer cells behavior can only be deciphered considering the contribution of the cells existing in the tumor stroma as well as its complex microenvironment. Since the tumor microenviron-ment plays an important role in cancer progression, it is widely accepted that culturing cells in 3D scaffolds, which mimic the native extracellular matrix, rep-resents a more realistic scenario. In the present work we aim to develop an in vitro 3D co-culture system that would comprise both cancer and stromal cells. For that, HeLa cells were injected into a RAD16-I peptide scaffold containing fibroblasts, resulting in a 3D system were cancer cells were embedded within a stromal cells matrix. With this system, we were able to study cancer cells behavior in a 3D context in terms of survival, migration and proliferation. Moreover, we have demonstrated that the anti-cancer effect of different pharmaceutical drugs (Gemcitabine, 5-Flu-orouracil and the ROCK inhibitor Y-27632) can be qualitatively and quantitatively evaluated on the 3D co-culture system developed. catalaLa recerca en cancer s’ha basat tradicionalment en els cultius cel·lulars en 2D, centrant-se sobretot en les cel·lules cancerigenes i la seva genetica anomala. No obstant, els tumors son actualment acceptats com a teixits complexos, i com a tals, necessiten senyals d’un ambient 3D per a formar estructures tissulars in vit-ro. A mes, el comportament de les cel·lules tumorals nomes pot ser desxifrat considerant tambe la con-tribucio de les cel·lules existents en l’estroma del tu-mor, aixi com del seu complex microambient. Ja que el microambient del tumor juga un paper important en la progressio del cancer, es ampliament acceptat que cultivar les cel·lules en scaffolds 3D, que imiten la matriu extracel·lular nativa, representa un escenari mes realista. En aquest treball tenim com a objectiu desenvolupar un sistema in vitro de co-cultiu 3D, que comprengui tant cel·lules cancerigenes com cel·lules estromals. Per a aixo, les cel·lules HeLa varen ser in-jectades en l’scaffold peptidic RAD16-I que contenia fibroblasts, resultant en un sistema 3D on les cel·lules cancerigenes quedaven rodejades per una matriu de cel·lules estromals. Amb aquests sistema hem sigut capacos d’estudiar el comportament de les cel·lules tumorals en un context 3D, en termes de superviven-cia, migracio i proliferacio. A mes a mes, hem demos-trat que l’efecte anti-cancerigen de diferents farmacs (Gemcitabina, 5-Fluorouracil i l’inhibidor de ROCK Y-27632) por ser qualitativament i quantitativament avaluat en el sistema de co-cultiu 3D desenvolupat.

The Never-Ending Story of Life, 2021

Macromolecular Materials and Engineering, 2019

Please correct your galley proofs carefully and return them no more than four days after the page... more Please correct your galley proofs carefully and return them no more than four days after the page proofs have been received. The editors reserve the right to publish your article without your corrections if the proofs do not arrive in time. Note that the author is liable for damages arising from incorrect statements, including misprints.

Materials, 2016

Adult articular cartilage has a limited capacity for growth and regeneration and, with injury, ne... more Adult articular cartilage has a limited capacity for growth and regeneration and, with injury, new cellular or biomaterial-based therapeutic platforms are required to promote repair. Tissue engineering aims to produce cartilage-like tissues that recreate the complex mechanical and biological properties found in vivo. In this study, a unique composite scaffold was developed by infiltrating a three-dimensional (3D) woven microfiber poly (ε-caprolactone) (PCL) scaffold with the RAD16-I self-assembling nanofibers to obtain multi-scale functional and biomimetic tissue-engineered constructs. The scaffold was seeded with expanded dedifferentiated human articular chondrocytes and cultured for four weeks in control and chondrogenic growth conditions. The composite constructs were compared to control constructs obtained by culturing cells with 3D woven PCL scaffolds or RAD16-I independently. High viability and homogeneous cell distribution were observed in all three scaffolds used during the term of the culture. Moreover, gene and protein expression profiles revealed that chondrogenic markers were favored in the presence of RAD16-I peptide (PCL/RAD composite or alone) under chondrogenic induction conditions. Further, constructs displayed positive staining for toluidine blue, indicating the presence of synthesized proteoglycans. Finally, mechanical testing showed that constructs containing the PCL scaffold maintained the initial shape and viscoelastic behavior throughout the culture period, while constructs with RAD16-I scaffold alone contracted during culture time into a stiffer and compacted structure. Altogether, these results suggest that this new composite scaffold provides important mechanical requirements for a cartilage replacement, while providing a biomimetic microenvironment to re-establish the chondrogenic phenotype of human expanded articular chondrocytes.

Evaluation of the self-assembling peptide RAD16-I as a support scaffold for chondrogenic differen... more Evaluation of the self-assembling peptide RAD16-I as a support scaffold for chondrogenic differentiation using dedifferentiated bovine chondrocytes.

Biomolecules, 2022

One of the most desirable properties that biomaterials designed for tissue engineering or drug de... more One of the most desirable properties that biomaterials designed for tissue engineering or drug delivery applications should fulfill is biodegradation and resorption without toxicity. Therefore, there is an increasing interest in the development of biomaterials able to be enzymatically degraded once implanted at the injury site or once delivered to the target organ. In this paper, we demonstrate the protease sensitivity of self-assembling amphiphilic peptides, in particular, RAD16-I (AcN-RADARADARADARADA-CONH2), which contains four potential cleavage sites for trypsin. We detected that when subjected to thermal denaturation, the peptide secondary structure suffers a transition from β-sheet to random coil. We also used Matrix-Assisted Laser Desorption/Ionization-Time-Of-Flight (MALDI-TOF) to detect the proteolytic breakdown products of samples subjected to incubation with trypsin as well as atomic force microscopy (AFM) to visualize the effect of the degradation on the nanofiber scaff...

The Never-Ending Story of Life, 2021

The essential principle of life perpetuation through uninterrupted life cycles of individual orga... more The essential principle of life perpetuation through uninterrupted life cycles of individual organisms is described in detail. During this process, life flows by acquiring many forms such as the gametes formed by individuals, gamete fusion (egg fertilization), embryogenesis, growth and development, adulthood, and sexual maturation, and again, another cycle of life is initiated. Nevertheless, the key factor for this process to operate is based on the basic principle that individuals have a finite lifespan while life is propagated indefinitely.

The Never-Ending Story of Life, 2021

Epilogue: The Future of Humankind Could Depend on Unicellular Life Summary It is very clear for m... more Epilogue: The Future of Humankind Could Depend on Unicellular Life Summary It is very clear for most of us that life in our planet is becoming more and more restricted in terms of having enough resources to support everyone's subsistence. This without question could cause in the near future a massive crisis for survival. But before this would happen, we could have one or two more chances to survive. Our first option is to solve our population growth dynamics, and the second is to prepare ourselves for a long trip to other worlds, outside our solar system. Both scenarios are considered to evaluate how we can contribute to the never-ending story of life.