In situ enabling approaches for tissue regeneration: Current challenges and new developments

This work was supported by National Funds from the FCT, Fundação para a Ciência e a Tecnologia, through the projects UID/Multi/50016/2019, UID/Multi/04044/2019, and POCI-01-0145-FEDER-31146, a post-doctoral fellowship to SB-S (SFRH/BPD/116024/2016), the European Union through PT2020 and Centro2020 (CENTRO-01-0145-FEDER-000014 and POCI-01-0247-FEDER-024533), the Fundo Europeu de Desenvolvimento Regional (FEDER) through the project NORTE-01-0145-FEDER-000012 (Biotherapies – Structured Programme on Bioengineering Therapies for Infectious Diseases and Tissue Regeneration) funded by the NORTE2020 program, and the Interreg V-A POCTEP Program through FEDER funds from the European Union (0245_IBEROS_1_E).In situ tissue regeneration can be defined as the implantation of tissue-specific biomaterials (by itself or in combination with cells and/or biomolecules) at the tissue defect, taking advantage of the surrounding microenvironment as a natural bioreactor. Up to now, the structures used were based on particles or gels. However, with the technological progress, the materials’ manipulation and processing has become possible, mimicking the damaged tissue directly at the defect site. This paper presents a comprehensive review of current and advanced in situ strategies for tissue regeneration. Recent advances to put in practice the in situ regeneration concept have been mainly focused on bioinks and bioprinting techniques rather than the combination of different technologies to make the real in situ regeneration. The limitation of conventional approaches (e.g., stem cell recruitment) and their poor ability to mimic native tissue are discussed. Moreover, the way of advanced strategies such as 3D/4D bioprinting and hybrid approaches may contribute to overcome the limitations of conventional strategies are highlighted. Finally, the future trends and main research challenges of in situ enabling approaches are discussed considering in vitro and in vivo evidence.info:eu-repo/semantics/publishedVersio

Role of SPARC in Bone Remodeling and Cancer‐Related Bone Metastasis

There is a growing socioeconomic recognition that clinical bone diseases such as bone infections, bone tumors and osteoporotic bone loss mainly associated with ageing, are major issues in today0s society. SPARC (secreted protein, acidic and rich in cysteine), a matricellular glycoprotein, may be a promising therapeutic target for preventing or treating bone‐related diseases. In fact, SPARC is associated with tissue remodeling, repair, development, cell turnover, bone mineralization and may also participate in growth and progression of tumors, namely cancer‐related bone metastasis. Yet, the function of SPARC in such biological processes is poorly understood and controversial. The main objective of this work is to review the current knowledge related to the activity of SPARC in bone remodeling, tumorigenesis, and bone metastasis. Progress in understanding SPARC biology may provide novel strategies for bone regeneration and the development of anti‐angiogenic, anti‐proliferative, or counter‐adhesive treatments specifically against bone metastasis

Fast decellularization process using supercritical carbon dioxide for trabecular bone

Decellularization is a process that consists on the removal of immunogenic cellular material from a tissue, so that it can be safely implanted as a functional and bioactive scaffold. Most decellularization protocols rely on the use of harsh chemicals and very long washing processes, leading to severe changes in the ultrastructure and loss of mechanical integrity. To tackle these challenges, supercritical carbon dioxide (scCO2) is herein proposed as an alternative methodology for assisting decellularization of porcine trabecular bone tissue and is combined, for the first time, with Tri(n-butyl) phosphate (TnBP). Histological and DNA analysis revealed that both TnBP and scCO2 were able to extract the DNA content from the scaffolds, being this effect more pronounced in treatments that used TnBP as a co-solvent. The combined protocol led to a decrease in DNA content by at least 90%, demon- strating the potential of this methodology and opening new possibilities for future optimizations.info:eu-repo/semantics/publishedVersio

In situ enabling approaches for tissue regeneration: current challenges and new developments

In situ tissue regeneration can be defined as the implantation of tissue-specific biomaterials (by itself or in combination with cells and/or biomolecules) at the tissue defect, taking advantage of the surrounding microenvironment as a natural bioreactor. Up to now, the structures used were based on particles or gels. However, with the technological progress, the materials’ manipulation and processing has become possible, mimicking the damaged tissue directly at the defect site. This paper presents a comprehensive review of current and advanced in situ strategies for tissue regeneration. Recent advances to put in practice the in situ regeneration concept have been mainly focused on bioinks and bioprinting techniques rather than the combination of different technologies to make the real in situ regeneration. The limitation of conventional approaches (e.g., stem cell recruitment) and their poor ability to mimic native tissue are discussed. Moreover, the way of advanced strategies such as 3D/4D bioprinting and hybrid approaches may contribute to overcome the limitations of conventional strategies are highlighted. Finally, the future trends and main research challenges of in situ enabling approaches are discussed considering in vitro and in vivo evidence.info:eu-repo/semantics/publishedVersio

AS REPRESENTAÇÕES SOCIAIS DE BELEZA NA INFÂNCIA: “ser bonito” tem seus limites

This text constitutes a study in a school of early childhood education in the municipality of Ananindeua-PA, with 24 children aged 5 years. Its problem is: what social representations do 5-year-old children have about beauty in early childhood education? Qualitative research (MINAYO, 2001) that combines theoretical and methodological references of social representations (MOSCOVICI, 2003; JODELET, 2001), Sociology of Childhood (CORSARO, 2011; SARMENTO, 2015). The results indicate that young children have social representations of beauty and anchor it to the care and attention they receive from the family, in affection and human relations, in social representations about the body influenced by the culture of consumption and in the "having things" and to the media.  Este texto es un extracto de una investigación realizada en un jardín de infancia de la ciudad de Ananindeua-PA, con 24 niños de 5 años. Su problema es: ¿Cuáles son las representaciones sociales que tienen los niños de 5 años sobre la belleza de la educación infantil? Investigación con enfoque cualitativo (MINAYO, 2001) que combina referencias teórico-metodológicas de representaciones sociales (MOSCOVICI, 2003; JODELET, 2001), Sociología de la Infancia (CORSARO, 2011; SARMENTO, 2015). Los resultados muestran que los niños pequeños tienen representaciones sociales de belleza y ancla, en la perspectiva del cuidado y atención que reciben de la familia, en el afecto y en las relaciones humanas, las representaciones sociales sobre el cuerpo y la cultura consumista asociada al 'tener cosas' y al difundido por los medios de comunicación.    Este texto constitui um recorte de pesquisa realizada em escola de educação infantil no município de Ananindeua-PA, com 24 crianças de 5 anos. Tem como problemática: quais as representações sociais que crianças de 5 anos possuem sobre beleza na educação infantil? Pesquisa de abordagem qualitativa (MINAYO, 2001) que combina referenciais teóricos-metodológicos das representações sociais (MOSCOVICI, 2003; JODELET, 2001), Sociologia da Infância (CORSARO, 2011; SARMENTO, 2015). Os resultados apontam que as crianças pequenas têm representações sociais de beleza e a ancoram ao cuidado e atenção que recebem da família, na afetividade e relações humanas, nas representações sociais sobre o corpo influenciadas na cultura do consumo e no “ter coisas” e ao difundido pela mídia.  

New prospects in skin regeneration and repair using nanophased hydroxyapatite embedded in collagen nanofibers

This study reflects an exploitation of a composite matrix produced by electrospinning of collagen and electrospraying of nanophased hydroxyapatite (nanoHA), for skin regeneration applications. The main goal was to evaluate the effect of nanoHA, as source of localized calcium delivery, on human dermal fibroblasts, keratinocytes, and human mesenchymal stem cells (hMSCs) growth, proliferation, differentiation, and extracellular matrix production. This study revealed that calcium ions provided by nanoHA significantly enhanced cellular growth and proliferation rates and prevented adhesion of pathogenic bacteria strains typically found in human skin flora. Moreover, hMSCs were able to differentiate in both osteogenic and adipogenic lineages. Rat subcutaneous implantation of the membranes also revealed that no adverse reaction occurred. Therefore, the mechanically fit composite membrane presents a great potential to be used either as cell transplantation scaffold for skin wound regeneration or as wound dressing material in plastic surgery, burns treatment or skin diseases.info:eu-repo/semantics/acceptedVersio

Analysis of an interaction situation through Rickelman's and Laing's theoretical frameworks

The authors utilized Rickelmall's Bio-Psycho-Social Linguistics Interaction Model and Laing's lnterpersonal Perception Theory categories to classify and describe an interaction situation, supposing that these theoretical frameworks were compatible. They concluded that, in despite of some identified convergent theoretic aspects, their practical application evidenced substantive differences, derived from philosophical basis, that raised difficulties or objections to their concomitant use.Se utilizó categorías del Modelo de Interacción Lingüística Bio-Psico-Social de Rickelman y de la Teoría de la Percepción Interpersonal de Laing para categorización y descripción de una situación interaccional, teniendo Como presupuesto que había compatibilidad entre estos dos referenciales teóricos. Se concluyó que, a pesar de haber sido identificados, desde el punto de vista teórico, aspectos concordantes entre sí, en la aplicación práctica, estos dos referenciales muestran algunas diferencias sustanciales, dependientes de su basamento filosófico, los cuales dificultan o no aconsejan su uso concomitante.Utilizou-se categorias do Modelo de Interação Lingüística Bio-Psico-Social de Rickelman e da Teoria da Percepção lnterpessoal de Laing para categorização e descrição de uma situação interacional, partindo-se do pressuposto de que havia compatibilidade entre estes dois referenciais teóricos. Concluiu-se que, apesar de haverem sido identificados, do ponto de vista teórico, aspectos concordantes entre eles, na aplicação prática esses dois referenciais evidenciam algumas diferenças substanciais, decorrentes de seu embasamento filosófico, que dificultam ou não aconselham seu uso concomitante

Behavior of prostate cancer cells in a nanohydroxyapatite/collagen bone scaffold

Prostate cancer (PCa) is the second leading cause of death among men in Europe and U.S. The metastatic dissemination pattern of PCa is unique, developing bone metastasis as the only site of progression, consequently with a prognosis very poor. The cancer cells interactions within the surrounding bone environment are critical for tumor growth and progression. Secreted protein, acidic and rich in cysteine (SPARC) is described to be involved in PCa cells migration and invasion into bone. Three-dimensional (3D) in vitro systems that are able to closely resemble the in vivo microenvironment are recently taking importance in cancer research. Original nanohydroxyapatite/collagen scaffolds were designed to resemble bone microenvironment in order to be applied as substitutes in bone defects and as potential biomaterials to mimic skeletal tumors. In fact, these 3D structures were cytocompatible and able to support osteoblast (MC3T3-E1) colonization and to promote bone ingrowth. Additionally, SPARC adsorption onto the scaffolds affected PC3 and LNCaP PCa cell lines behavior. PC3 cells were found to adapt and colonize the scaffolds, differing from LNCaP where cells underwent morphogenic changes and grew as clusters. Furthermore, for the tested SPARC concentration, SPARC plays a role in retaining LNCaP cells at the latter time points while with PC3 cells no significant differences were observed. This characterization study is required to establish a bone model to provide new insights into the poorly understood PCa mechanisms of metastasis to bone and the generation of improved therapies.info:eu-repo/semantics/publishedVersio

Sterile and dual-porous aerogels scaffolds obtained through a multistep supercritical CO2-based approach

Aerogels from natural polymers are endowed with attractive textural and biological properties for biomedical applications due to their high open mesoporosity, low density, and reduced toxicity. Nevertheless, the lack of macroporosity in the aerogel structure and of a sterilization method suitable for these materials restrict their use for regenerative medicine purposes and prompt the research on getting ready-to-implant dual (macro + meso)porous aerogels. In this work, zein, a family of proteins present in materials for tissue engineering, was evaluated as a sacrificial porogen to obtain macroporous starch aerogels. This approach was particularly advantageous since it could be integrated in the conventional aerogel processing method without extra leaching steps. Physicochemical, morphological, and mechanical characterization were performed to study the effect of porogen zein at various proportions (0:1, 1:2, and 1:1 zein:starch weight ratio) on the properties of the obtained starch-based aerogels. From a forward-looking perspective for its clinical application, a supercritical CO2 sterilization treatment was implemented for these aerogels. The sterilization efficacy and the influence of the treatment on the aerogel final properties were evaluated mainly in terms of absence of microbial growth, cytocompatibility, as well as physicochemical, structural, and mechanical modifications.Work supported by Xunta de Galicia [ED431F 2016/010 & ED431C 2016/008], MINECO [SAF2017-83118R], AEI, FEDER and Interreg VAPOCTEP Programme [0245_IBEROS_1_E].C.A.García-González acknowledges to MINECO for a Ramón y Cajal Fellowship [RYC2014-15239]. V. Santos-Rosales acknowledges to Xunta de Galicia (Consellería de Cultura, Educación e Ordenación Universitaria) for a predoctoral research fellowship [ED481A-2018/014]. A.L. Oliveira acknowledges Portuguese National Funds from FCT—Fundação para a Ciência e a Tecnologia through Program FCT Investigator (IF/00411/2013), project SERICAMED (IF/00411/2013/CP1167) and project UID/Multi/50016/2013. Work carried out in the frame of the COST-Action “Advanced Engineering and Research of aeroGels for Environment and Life Sciences” (AERoGELS, ref. CA18125) funded by the European CommissionS