Carbon Nanomaterial-Based Hydrogels as Scaffolds in Tissue Engineering: A Comprehensive Review.

Carbon-based nanomaterials (CBNs) are a category of nanomaterials with various systems based on combinations of sp2 and sp3 hybridized carbon bonds, morphologies, and functional groups. CBNs can exhibit distinguished properties such as high mechanical strength, chemical stability, high electrical conductivity, and biocompatibility. These desirable physicochemical properties have triggered their uses in many fields, including biomedical applications. In this review, we specifically focus on applying CBNs as scaffolds in tissue engineering, a therapeutic approach whereby CBNs can act for the regeneration or replacement of damaged tissue. Here, an overview of the structures and properties of different CBNs will first be provided. We will then discuss state-of-the-art advancements of CBNs and hydrogels as scaffolds for regenerating various types of human tissues. Finally, a perspective of future potentials and challenges in this field will be presented. Since this is a very rapidly growing field, we expect that this review will promote interdisciplinary efforts in developing effective tissue regeneration scaffolds for clinical applications.

In vitro high-content tissue models to address precision medicine challenges.

The field of precision medicine allows for tailor-made treatments specific to a patient and thereby improve the efficiency and accuracy of disease prevention, diagnosis, and treatment and at the same time would reduce the cost, redundant treatment, and side effects of current treatments. Here, the combination of organ-on-a-chip and bioprinting into engineering high-content in vitro tissue models is envisioned to address some precision medicine challenges. This strategy could be employed to tackle the current coronavirus disease 2019 (COVID-19), which has made a significant impact and paradigm shift in our society. Nevertheless, despite that vaccines against COVID-19 have been successfully developed and vaccination programs are already being deployed worldwide, it will likely require some time before it is available to everyone. Furthermore, there are still some uncertainties and lack of a full understanding of the virus as demonstrated in the high number new mutations arising worldwide and reinfections of already vaccinated individuals. To this end, efficient diagnostic tools and treatments are still urgently needed. In this context, the convergence of bioprinting and organ-on-a-chip technologies, either used alone or in combination, could possibly function as a prominent tool in addressing the current pandemic. This could enable facile advances of important tools, diagnostics, and better physiologically representative in vitro models specific to individuals allowing for faster and more accurate screening of therapeutics evaluating their efficacy and toxicity. This review will cover such technological advances and highlight what is needed for the field to mature for tackling the various needs for current and future pandemics as well as their relevancy towards precision medicine.

3D Bioprinting of Smart Oxygen-Releasing Cartilage Scaffolds.

Three-dimensional bioprinting is a powerful technique for manufacturing improved engineered tissues. Three-dimensional bioprinted hydrogels have significantly advanced the medical field to repair cartilage tissue, allowing for such constructs to be loaded with different components, such as cells, nanoparticles, and/or drugs. Cartilage, as an avascular tissue, presents extreme difficulty in self-repair when it has been damaged. In this way, hydrogels with optimal chemical and physical properties have been researched to respond to external stimuli and release various bioactive agents to further promote a desired tissue response. For instance, methacryloyl gelatin (GelMA) is a type of modified hydrogel that allows for the encapsulation of cells, as well as oxygen-releasing nanoparticles that, in the presence of an aqueous medium and through controlled porosity and swelling, allow for internal and external environmental exchanges. This review explores the 3D bioprinting of hydrogels, with a particular focus on GelMA hydrogels, to repair cartilage tissue. Recent advances and future perspectives are described.

Production of rGO-Based Electrospinning Nanocomposites Incorporated in Recycled PET as an Alternative Dry Electrode.

In this work, Coca-Cola® bottles were reused as a PET polymer (rPET) source to produce electrospun polymeric nanofibers. The nanofibers were electrospun from polymer solutions with different concentrations of reduced graphene oxide (rGO) incorporated for applications in somatosensory electrical stimulation. The rPET/rGO nanofiber mats were characterized by SEM, TEM, Raman, DSC, TGA, and DMA and the results showed that the incorporation of rGO in electrospun rPET fibers produced rPET/rGO composites. The rPET/rGO composites were then evaluated for possible application as dry electrodes. Moreover, with a preliminary test of numerous volunteers, the rPET/rGO dry electrode showed promising results. The rPET/rGO electrodes showed good performance and applicability to make dry electrodes, and these have applications as dry or wearable electrodes to produce electrochemical sensors.

Towards Bioinspired Meniscus-Regenerative Scaffolds: Engineering a Novel 3D Bioprinted Patient-Specific Construct Reinforced by Biomimetically Aligned Nanofibers.

Introduction: Three of the main requirements that remain major challenges in tissue engineering of the knee meniscus are to engineer scaffolds with compatible anatomical shape, good mechanical properties, and microstructure able to mimic the architecture of the extracellular matrix (ECM). In this context, we presented a new biofabrication strategy to develop a three-dimensional (3D) meniscus-regenerative scaffold with custom-made macroscopic size and microarchitecture bioinspired by the organization of structural fibers of native tissue ECM. Methods: The concept was based on the combination of bioprinted cell-laden hydrogel (type 1 collagen) reinforced by multilayers of biomimetically aligned electrospun nanofibrous mats (polycaprolactone/carbon nanotubes, PCL/CNT), using a patient-specific 3D digital meniscus model reconstructed from MRI data by free and open-source software. Results: The results showed that the incorporation of aligned nanofibers sheets between the hydrogel layers enhanced the scaffold's structural integrity and shape fidelity compared to the nanofiber-free collagen hydrogel. Furthermore, mechanical compression tests demonstrated that the presence of nanofiber layers significantly improved the mechanical properties of the bioprinted construct. Importantly, the introduction of PCL/CNT nanofibrous mats between the layers of the bioprinted collagen hydrogel did not negatively affect cell viability, in which mesenchymal stem cells remained viable even after 7 days of culture within the scaffold. Conclusion: Overall, these findings evidence that this bioengineering approach offers a promising strategy for fabricating biomimetic meniscus scaffolds for tissue engineering.

Nanohydroxyapatite Electrodeposition onto Electrospun Nanofibers: Technique Overview and Tissue Engineering Applications.

Nanocomposite scaffolds based on the combination of polymeric nanofibers with nanohydroxyapatite are a promising approach within tissue engineering. With this strategy, it is possible to synthesize nanobiomaterials that combine the well-known benefits and advantages of polymer-based nanofibers with the osteointegrative, osteoinductive, and osteoconductive properties of nanohydroxyapatite, generating scaffolds with great potential for applications in regenerative medicine, especially as support for bone growth and regeneration. However, as efficiently incorporating nanohydroxyapatite into polymeric nanofibers is still a challenge, new methodologies have emerged for this purpose, such as electrodeposition, a fast, low-cost, adjustable, and reproducible technique capable of depositing coatings of nanohydroxyapatite on the outside of fibers, to improve scaffold bioactivity and cell-biomaterial interactions. In this short review paper, we provide an overview of the electrodeposition method, as well as a detailed discussion about the process of electrodepositing nanohydroxyapatite on the surface of polymer electrospun nanofibers. In addition, we present the main findings of the recent applications of polymeric micro/nanofibrous scaffolds coated with electrodeposited nanohydroxyapatite in tissue engineering. In conclusion, comments are provided about the future direction of nanohydroxyapatite electrodeposition onto polymeric nanofibers.

Oxygen-generating smart hydrogels supporting chondrocytes survival in oxygen-free environments.

Cartilage is one of our body's tissues which are not repaired automatically by itself. Problems associated with cartilage are very common worldwide and are considered the leading cause of pain and disability. Smart biomaterial or "Four dimensional" (4D) biomaterials has started emerging as a suitable candidate, which are principally three dimensional (3D) materials that change their morphology or generate a response measured at space and time to physiologic stimuli. In this context, the release of oxygen through hydrogels in contact with water is considered as 4D biomaterials. The objective of this study is to develop strategies to release oxygen in a sustainable and prolonged manner through hydrogels systems to promote chondrocytes survival in oxygen-free environment. The 4D biomaterials are engineered from gelatin methacryloyl (GelMA) loaded with calcium peroxide (CPO), which have the ability to generate oxygen in a controlled and sustained manner for up to 6 days. The incorporation of CPO into the hydrogel system provided materials with enhanced mechanical and porosity properties. Furthermore, the hydrogels promoted chondrocyte survival and reduced cell death under oxygen-free conditions.

Propriocepção do joelho em indivíduos submetidos à menistectomia parcial e à sutura meniscal: estudo observacional / Knee proprioception in individuals submitted to partial menistectomy and meniscal repair: observational study

Os meniscos desempenham um papel fundamental na articulação, além de gerar estabilidade e congruência articular, influenciam na propriocepção do joelho. Lesões nesta estrutura muitas vezes só podem ser reparadas cirurgicamente, pelo fraco suprimento sanguíneo local, acarretando uma regeneração insatisfatória. A hipótese desse estudo é que possa existir menores déficits proprioceptivos em pacientes submetidos à sutura meniscal quando comparados aos submetidos à menistectomia parcial, devido a conservação da estrutura que tem importância proprioceptiva. OBJETIVO: Avaliar o déficit proprioceptivo do joelho em pacientes submetidos à menistectomia parcial e à sutura meniscal. METODOLOGIA: Estudo observacional transversal realizado na clínica de ortopedia e reumatologia da UNISA, em São Paulo. Participantes foram divididos em dois grupos. No Grupo I, indivíduos submetidos à menistectomia parcial, enquanto no Grupo II, a submetidos à sutura meniscal, sendo recrutados indivíduos de até 4 semanas de pós-operatório. Aprovado pelo comitê de ética seguido pelo CAAE 94144218.0.0000.0081. Para coleta dos dados foram realizados três testes: teste de senso de posicionamento ativo e passivo e teste de cinestesia. RESULTADOS: Participaram deste estudo uma amostra por conveniência de oito indivíduos (Grupo I, n=4 e Grupo 2, n=4), de ambos os gêneros, com média de idade de 33,4 anos (±11 anos). Os sujeitos do grupo I apresentaram maior déficit de proprioceptivo em comparação com o grupo II, nos testes realizados. Teste ativo do grupo I: 15°= 11,9° ±6,1; 30°= 11,6° ±5,0; 45°= 9,4° ±3,5 e do grupo II, 15°= 7,6° ±3,9; 30°= 6,9° ±2,8. Teste de Cinestesia: Grupo I 132ms ±51,5 vs Grupo II 96ms ±28,8). CONCLUSÃO: Os meniscos demonstraram ser estruturas influentes para a propriocepção do joelho, apresentando maiores déficits em indivíduos que retiraram a estrutura.

Menisci play a fundamental role in the joint, in addition to generating joint stability and congruence, they influence knee proprioception. Lesions in this structure can often only be repaired surgically, due to the weak local blood supply, leading to unsatisfactory regeneration. The hypothesis of this study is that there may be less proprioceptive deficits in patients undergoing meniscal suture when compared to those undergoing partial menistectomy. OBJECTIVE: To evaluate the proprioceptive deficit of the knee in patients undergoing partial menistectomy and meniscal suture. METHODS: Cross-sectional observational study carried out at the UNISA orthopedics and rheumatology clinic in São Paulo. Participants were divided into two groups. In Group I, individuals who underwent partial menistectomy, while in Group II, who underwent meniscal suture, individuals were recruited up to 4 weeks after surgery. Approved by the ethics committee followed by CAAE 94144218.0.0000.0081. For data collection, three tests were performed: test of active and passive sense positioning and kinesthesia test. RESULTS: Four individuals participated in Group I and four individuals in Group II, of both genders, between 20 and 40 years old. The results indicate that the patients who underwent partial menistectomy and meniscal suture showed proprioceptive differences between the operated and the non-operated limbs, however the subjects who had the preserved structure presented smaller values of difference in comparison with the operated members of the two groups (Active Test: 30 ° = Group I 11.6 ° ± 5.0 vs Group II 6.9 ° ± 2.8, p = 0.010; 45 ° = Group I 9.4 ° ± 3.5 vs Group II 6.5 ° ± 2.8, p = 0.035; 60 ° = Group I 9.7 ° ± 4.3 vs Group II 6.5 ° ± 4.9, p = 0.103; Kinesthesia Test: Group I 132ms ± 51.5 vs Group II 96ms ± 28.8, p = 0.046). CONCLUSION: Higher proprioceptive deficits were found in subjects undergoing menistectomy compared to the sutured limb group, with a statistically significant difference.

Efeito agudo de diferentes métodos de termoterapia na amplitude de movimento articular / Acute effect of different thermotherapy methods on articular range of motion

Objetivo O objetivo deste estudo foi comparar quantitativamente o efeito agudo de diferentes técnicas de termoterapia no ganho da amplitude de movimento. Participaram da pesquisa voluntários (n=34) de ambos os sexos e média de idade de 22,3 anos (±3,3 anos). Métodos Os participantes foram divididos aleatoriamente em dois grupos: em um grupo, os indivíduos foram submetidos a aplicação da lâmpada infravermelha (calor superfi cial), enquanto no outro grupo utilizou-se o aparelho de ondas curtas (calor profundo) como técnica de termoterapia. Resultados Como resultado, observou-se que o grupo submetido ao calor profundo obteve melhora significante em relação a amplitude de movimento, tanto em comparação dentro do mesmo grupo, confrontando-se a amplitude de movimento pré- e pós-intervenção (aumento médio de 10,9+3,1º), quanto quando comparado ao grupo submetido ao calor superficial, que não apresentou melhora significativa (aumento médio de 3,1+2,5º). Conclusão Concluiu-se que, embora o efeito agudo da termoterapia seja benéfico no ganho de amplitude de movimento, o calor profundo parece ter um efeito mais pronunciado quando comparado às técnicas de calor superficial.

Objective The objective of this study was to quantitatively compare the acute effect of different thermotherapy techniques on the gain of range of motion. Methods Research volunteers (n=34) of both genders and mean age of 22.3 years (±3.3 years) were randomly divided into two groups: one group in which subjects were treated with infrared lamp (surface heat) while the other group was treated with the selected thermotherapy technique with the shortwave apparatus (deep heat). Results The deep heat group obtained a significant improvement in terms of range of motion, both within the same group, comparing the pre and post intervention range of motion (mean increase of 10.9±3.1º) when compared to the superficial heat group, which in turn did not show significant improvement (mean increase of 3.1+2.5º). Conclusion Although the acute effect of thermotherapy is beneficial in gain of range of motion, deep heat seems to have a more pronounced effect when compared to surface heat techniques

Cell Viability of Porous Poly(d,l-lactic acid)/Vertically Aligned Carbon Nanotubes/Nanohydroxyapatite Scaffolds for Osteochondral Tissue Engineering.

Treatment of articular cartilage lesions remains an important challenge. Frequently the bone located below the cartilage is also damaged, resulting in defects known as osteochondral lesions. Tissue engineering has emerged as a potential approach to treat cartilage and osteochondral defects. The principal challenge of osteochondral tissue engineering is to create a scaffold with potential to regenerate both cartilage and the subchondral bone involved, considering the intrinsic properties of each tissue. Recent nanocomposites based on the incorporation of nanoscale fillers into polymer matrix have shown promising results for the treatment of osteochondral defects. In this present study, it was performed using the recently developed methodologies (electrodeposition and immersion in simulated body fluid) to obtain porous superhydrophilic poly(d,l-lactic acid)/vertically aligned carbon nanotubes/nanohydroxyapatite (PDLLA/VACNT-O:nHAp) nanocomposite scaffolds, to analyze cell behavior and gene expression of chondrocytes, and then assess the applicability of this nanobiomaterial for osteochondral regenerative medicine. The results demonstrate that PDLLA/VACNT-O:nHAp nanocomposite supports chondrocytes adhesion and decreases type I Collagen mRNA expression. Therefore, these findings suggest the possibility of novel nanobiomaterial as a scaffold for osteochondral tissue engineering applications.