Influence of viscosity and velocity of administration on the performance of hyaluronic acid as a vehicle for bioprinting and injectable cell therapy: a computer simulation approach and in vitro validation

Background: Hyaluronic acid (HA) is a natural polymer widely used as a vehicle in injectable cell therapy for the treatment of arthropathies. Objective: To estimate, through computational simulations and in vitro validation, the influence of HA’s physicochemical properties and administration speed on the shear stress generated in the syringe/needle system, as well as the associated risk to cell viability during administration. Methods: The influence of viscosity was evaluated by considering the rheological parameters corresponding to HA concentrations of 6, 8, 10, 12, and 15 mg/mL. For assessing the impact of administration speed, values representative of the typical speed range used in clinical procedures were considered. Simulations were used to estimate shear stress as a function of administration speed for each viscosity level. Results: The findings revealed a directly proportional relationship between viscosity and administration speed with the magnitude of shear stress. Notably, the highest viscosity formulation, when administered at the fastest speed, reached "critical values" of shear stress associated with mechanical damage to cell membranes and cell death. Conversely, lower viscosity HA exhibited reduced stress levels, indicating it as the potentially preferred formulation for injectable cell therapy. The in vitro cell culture assays corroborated the computational simulation results. Conclusions: The administration of HA demonstrates a viscosity- and speed-dependent effect on shear stress, which should be carefully considered for its application in bioprinting and injectable cell therapies

A Brief Review on Metamaterials Applied to the Healthcare Field

Metamaterials refer to any modification of the physical behavior of an existing material through the structured arrangement of repetitive patterns, procedurally generated, which can directly influence its response to deformation, thermal dissipation, and vibrational control. This creates possibilities for solutions that were previously difficult to achieve using conventional materials such as metals, ceramics, polymers, and their composites. The use of this technology has gained momentum with the advent of 3D printing, which has made it possible to apply and create these structures for practical validation. The first structures were modeled at the beginning of the last century, such as the creation of patterns to generate anomalous properties, with diverse applications in fields like optics, thermodynamics, and mechanics, as it allows for material design tailored to specific applications. As a result, applications have expanded to various scales, from millimeter-engineered materials to the nanoscale, drawing the attention of researchers from different fields, including healthcare. This interest stems from the vast array of possibilities and innovations driven by advancements in materials and additive manufacturing, combining these fields to generate increasingly adaptive solutions. In this paper, the concept of metamaterials will be introduced, followed by an exploration of various applications of this technology, including medical equipment, devices, prosthetics, orthotics, and implants, as well as potential future applications of this technology in healthcare

Special Edition Submission: Dr. Jorge Vicente Lopes da Silva

There are texts that are easy to write and then there are others that have such an emotional significance that are much harder. I was invited to write about Jorge Vicente Lopes da Silva, a Brazilian researcher that had and continues to have a worldwide impact in the scientific, academic and industrial domain. He had a significant scientific contribution worldwide, but his greatest impact was the friendships that he created with everyone that had the opportunity of meeting him

The pharmaceutical patent process: National Health Surveillance Agency and National Institute of Industrial Property act differently in the process

The National Institute of Industrial Property (INPI) is the government body responsible for granting patents in the national territory; in the case of medicines, they need to be registered with the National Health Surveillance Agency (ANVISA) in order to be marketed. There was a divergence in legal interpretation (of Art. 229-C of the IPL) which caused damage to entrepreneurs, laboratories and the community in general, as there was no express provision as to whether ANVISA's opinion would be binding on the INPI's decision on patent issues. The aim of this research was to analyze this problem, raising its main points and demonstrating how dangerous and damaging bureaucracy and inefficient and obscure normative acts that give rise to dubious interpretation can be, based on the application of hermeneutic and dialectical methods. In 2021, the Superior Court of Justice (STJ), in Special Appeal n. 1543826, held that ANVISA's opinion would be a valid prerequisite for granting patents for pharmaceutical products or processes. It was found that the STJ decision increased ANVISA's "powers", but with the repeal of Art. 229-C of the IPL, the dilemma was extinguished and the competencies of each body re-established. It is therefore of the utmost importance to fill legal gaps and issue clear and specific laws so as not to leave room for harmful interpretations, guaranteeing original competences and legal certainty

Bioprinting for Skin: Current Approaches, Technological Advancements and the Role of Artificial Intelligence: Bioprinting for Skin: Approaches, Advancements and Artificial Intelligence

Bioprinting is a technique adapted from 3D printing to create biological constructs, including high-quality skin substitutes. It matches or exceeds the quality of traditional fabrication methods, offering precision, consistency and speed, critical attributes for large-scale production. A variety of materials are used, most of them natural, such as alginate, chitosan and gelatin, with cells incorporated into the bioink. These cells may belong to the replicated tissue or include stem cells that can differentiate into the desired cell types. Bioprinting enables precise placement of the skin’s layers: hypodermis, dermis and epidermis, allowing for replication of the skin’s complex architecture. Notably, bioprinted skin constructs can closely resemble native tissue, even forming structures like hair follicles and glands as the incorporated cells grow, migrate and differentiate. Artificial intelligence (AI) and machine learning (ML) have recently been applied to enhance efficiency, precision and success. AI tools reduce trial and error by optimizing parameters, bioink composition and quality control. This review explores bioprinting methods, materials and advancements, including in situ bioprinting, the use of robotic devices and the emerging role of artificial intelligence

Photoluminescent gels based on han purple: new frontiers in biotechnology

As a result of the increasing need for new biocompatible materials, polymer-based gels have become promising options. Lately, photoluminescent gels have shown potential for applications in biotechnology and non-invasive tracking due to their ability to emit light when temperature changes occur. This research investigates the incorporation of Han Purple (HP) pigment into a polyethylene glycol/Laponite matrix [92,5/7,5%] (P7LHP0%) to produce a 3D-printed gel. The gels were examined for possible use as smart sensors, focusing on their optical and thermal characteristics.  Formulations with HP concentrations of 0.0%, 0.5%, and 2.0% were prepared, followed by extrusion-based 3D printing. Characterization techniques included FTIR, SEM, and optical analyses (emission and excitation spectra). The findings showed 3D structures with good shape fidelity while FTIR indicated suitable compatibility between HP and the matrix. Optical analysis revealed fluorescence with an excitation band between 400 and 700 nm, with a maximum at 620 nm, and an emission band at 830 - 1000 nm with a peak at 925 nm. This study highlights the potential of HP as a promising material for fluorescent gels in 3D printing, creating new opportunities for biotechnology application

Endocrine activities modulated by adipose-mesenchymal stem cell in an animal model induced to polycystic ovary syndrome

Purpose - Animal models offer a useful way to study the reproductive and metabolic abnormalities, including PCOS. MSCs have received increasing attention as a potential cell-based therapy and regenerative medicine, due to their effects in modulation of different molecular and biological pathways. The aims of the present work were to investigate modulation of the ovarian microenvironment by AdMSCs in an animal model induced to PCOS. Methods - Female rats were divided into control, polycystic ovary, and mesenchymal stem cell groups, evaluated at two different times after PCOS induction and injection of AdMSCs. Results - The polycystic ovary group showed changes in ovarian cycles, the presence of cysts in the ovaries, and hyperandrogenemia. In addition, changes in plasma insulin, glucose, leptin, and osteocalcin were observed in the polycystic ovary group. These metabolic changes were modulated by the injection of AdMSCs into the ovary. Data are presented for female rats in an animal model integrating PCOS with AdMSCs, together with the relationships among ovaries, bones, and adipocytes. Conclusion - The results suggested the existence of endocrine-metabolic-reproductive microenvironment relationships modulated by AdMSCs, which should help in guiding further investigations to clarify pathophysiological mechanisms that have not yet been fully elucidated

Induction of mineralized matrix production by recombinant human BMP-2 Immobilized in TEMPO-Oxidized Cellulose Hydrogel: a novel target for tissue repair

Bone morphogenetic proteins (BMPs) are potent promoters of osteogenesis, especially BMP-2, which has been highlighted for acting as a growth and differentiation factor that promotes new bone formation. There are several biomaterials that can be used to release bioactive substances, such as natural polymers. Cellulose has stood out for the possibility of its chemical modification using the reagent 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) to obtain a cellulose derivative (TEMPO oxidized cellulose nanofibers - ToCNF), which is shown to be a promising material for biological application. The objective of this work was to evaluate TEMPO cellulose immobilized with rhBMP-2 against the activity of inducing bone cell proliferation and differentiation in vitro, evaluating the ability to form bone matrix in pre-osteoblastic cell lineage of rats - MC3T3. Cell viability assays using resazurin were performed and for detection of mineralized matrix, Alizarin Red solution was used. The results reveal the good capacity of TEMPO cellulose functionalized with rhBM-2 in inducing the synthesis of mineralized bone matrix

Characterization of 3D-Printed B-TCP Scaffolds with Enhanced Microstructure, Mechanical Properties, and Cell Compatibility

Achieving bone regeneration in large defects caused by trauma, pathology and atrophy is a challenge. Innovative implant materials are emerging as alternatives to autografts in regenerative medicine. 3D-printed B-tricalcium phosphate (B-TCP) scaffolds have emerged as a promising solution for bone tissue replacement, offering patient-specific implants without relying on donors or transplantation. There are many open questions that need to be addressed before they can be used on a large scale. The analysis of sintering temperatures and the different crystalline phases, the in-depth evaluation of the microstructure and its biological response, as well as the assessment of suitable mechanical properties are some of these. The present study carried out a comprehensive characterization of the microstructure of commercial 3D-printed B-TCP using X-ray diffraction coupled with Rietveld refinement, X-ray microtomography and scanning electron microscopy. In addition, blood and cell compatibility tests were carried out using MG63 cells. The imaging techniques revealed the influence of the sintering treatment on the microstructure, resulting in an increase in the average pore size, efficient coalescence between particles and a shrinkage effect at higher temperatures. This behavior had a direct impact on the mechanical properties and cell adhesion behavior. Blood compatibility showed no significant differences between all the samples. However, the material sintered at 1200 °C showed better mechanical properties and a better behavior in the adhesion and proliferation of MG63, which were correlated with a higher density, improved mechanical properties and interconnected porosity, which play a key role in improving osteoblastic function

Development of PCLMA/HAp-Si composite resin for vat photopolymerization 3D printing

A photopolymerizable composite resin based on polycaprolactone methacrylate (PCLMA) was developed with functionalized hydroxyapatite (HAp-Si) to enhance the phase affinity between the polymer matrix and inorganic filler, thereby creating a stable resin suitable for 3D printing. Hydroxyapatite was functionalized with 3-aminopropyltrimethoxysilane (APTES) to produce HAp-Si, as confirmed by Fourier Transform Infrared Spectroscopy (FTIR). Polycaprolactone diol (PCLdiol) was successfully modified into PCLMA through the substitution of hydroxyl groups with methacrylate groups, as confirmed by FTIR, which also resulted in an increase in the number-average molecular weight (Mn). Scanning Electron Microscopy (SEM) images confirmed well-dispersed HAp agglomerates, while grafting improved filler distribution within the matrix. Additionally, the resin displayed good dimensional fidelity in 3D printing of cylindrical samples measuring 6.35 x 12.70 mm. These findings suggest that PCLMA-based composite resins are suitable for 3D printing via vat photopolymerization