Tissue Engineering Technology Research Articles

Bioprinting of human dermal microtissues precursors as building blocks for endogenous in vitro connective tissue manufacturing

The advent of 3D bioprinting technologies in tissue engineering has unlocked the potential to fabricate in vitro tissue models, overcoming the constraints associated with the shape limitations of preformed scaffolds. However, achieving an accurate mimicry of complex tissue microenvironments, encompassing cellular and biochemical components, and orchestrating their supramolecular assembly to form hierarchical structures while maintaining control over tissue formation, is crucial for gaining deeper insights into tissue repair and regeneration. Building upon our expertise in developing competent three-dimensional tissue equivalents (e.g. skin, gut, cervix), we established a two-step bottom-up approach involving the dynamic assembly of microtissue precursors (μTPs) to generate macroscopic functional tissue composed of cell-secreted extracellular matrix (ECM). To enhance precision and scalability, we integrated extrusion-based bioprinting technology into our established paradigm to automate, control and guide the coherent assembly of μTPs into predefined shapes. Compared to cell-aggregated bioink, our μTPs represent a functional unit where cells are embedded in their specific ECM. μTPs were derived from human dermal fibroblasts dynamically seeded onto gelatin-based microbeads. After 9 days, μTPs were suspended (50% v/v) in Pluronic-F127 (30% w/v) (µTP:P30), and the obtained formulation was loaded as bioink into the syringe of the Dr.INVIVO-4D6 extrusion based bioprinter. µTP:P30 bioink showed shear-thinning behavior and temperature-dependent viscosity (gel at T > 30 °C), ensuring µTPs homogenous dispersion within the gel and optimal printability. The bioprinting involved extruding several geometries (line, circle, and square) into Pluronic-F127 (40% w/v) (P40) support bath, leveraging its shear-recovery property. P40 effectively held the bioink throughout and after the bioprinting procedure, until µTPs fused into a continuous connective tissue. µTPs fusion dynamics was studied over 8 days of culture, while the resulting endogenous construct underwent 28 days culture. Histological, immunofluorescence analysis, and second harmonic generation reconstruction revealed an increase in endogenous collagen and fibronectin production within the bioprinted construct, closely resembling the composition of the native connective tissues.

Co-culture of RhoA-overexpressed Microtia Chondrocytes and Adipose-Derived Stem Cells in the Construction of Tissue-engineered Ear-shaped Cartilage.

Microtia is a congenital auricle dysplasia with a high incidence and tissue engineering technology provides a promising strategy to reconstruct auricles. We previously described that the engineered cartilage constructed from microtia chondrocytes exhibited inferior levels of biochemical and biomechanical properties, which was proposed to be resulted from the decreased migration ability of microtia chondrocytes. In the current study, we found that Rho GTPase members were deficient in microtia chondrocytes. By overexpressing RhoA, Rac1 and CDC42, respectively, we further demonstrated that RhoA took great responsibility for the decreased migration ability of microtia chondrocytes. Moreover, we constructed PGA/PLA scaffold-based cartilages to verify the chondrogenic ability of RhoA overexpressed microtia chondrocytes, and the results showed that overexpressing RhoA was of limited help to improve the quality of microtia chondrocyte engineered cartilage. However, co-culture of ADSCs significantly improved the biochemical and biomechanical property of engineered cartilage. Especially, co-culture of RhoA overexpressed microtia chondrocytes and ADSCs produced an excellent effect on the wet weight, cartilage-specific extracellular matrix and biomechanical property of engineered cartilage. Furthermore, we presented that co-culture of RhoA overexpressed microtia chondrocytes and ADSCs combined with human ear-shaped PGA/PLA scaffold and titanium alloy stent fabricated by CAD/CAM and 3D printing technology effectively constructed and maintained auricle structure in vivo. Collectively, our results provide evidence for the essential role of RhoA in microtia chondrocytes and a developed strategy for the construction of patient-specific tissue-engineered auricular cartilage.

Bogdan N. Kotiv — surgeon, professor, general of medicine (on the 60th anniversary of his birth)

March 14, 2024, marked the 60th anniversary of Bogdan N. Kotiv, the Deputy Head of the Military Medical Academy named after S.M. Kirov for clinical work, abnormal chief surgeon of the Academy, Honorary Doctor of the Russian Federation, Doctor of Medical Sciences, Professor, and Major General of the Medical Service. After graduating from the academy, B.N. Kotiv served in the Transcaucasian Military District as a leading surgeon in a separate medical battalion. In 1988, a young military surgeon participated in the provision of assistance to victims of the earthquake in the city of Spitak (Armenia) and received the first experience in providing medical care in military field conditions. In 1990, B.N. Kotiv entered the adjunct school at the Department of General Surgery, and in 1993, he successfully defended his dissertations for the degree of candidate of medical sciences. In 1998, the dissertation for the Doctor of Medical Sciences degree was brilliantly defended. In 2006, Bogdan N. Kotiv headed the Department of Hospital Surgery. When it was going through difficult times, a reorganization of the educational process occurred. Bogdan N. carefully preserved the traditions of teaching thoracic surgery and actively introduced the experience of modern complex surgical interventions into the educational process, including on the abdominal organs. The surgical school of the Department of Hospital Surgery rapidly took a leading position. In 2013, B.N. Kotiv was appointed the Deputy Head of the Academy for Academic and Scientific Work. Since 2021, Bogdan N. Kotiv has been the Deputy Head of the Academy for Clinical Work. He controlled and coordinated the clinical base of the academy, organized interactions with military hospitals throughout the country, and often went on business trips. At the beginning of a special military operation, a colossal responsibility fell on his shoulders. There was a need to quickly solve the permanently emerging problems of organizing the provision of medical care to the wounded in the conditions of the Academy clinics. With his direct participation, the clinical base was redesigned, its bed capacity was expanded, and new technologies for providing specialized medical care to the wounded, sick, and injured were introduced. For several generations of surgeons, Bogdan N. has been a wise mentor and role model. Under the leadership of Bogdan N. Kotiv, the range of scientific research conducted at the academy has significantly expanded. The fundamental directions of medicine for the study of the molecular and cellular foundations of combat lesions and cellular and tissue engineering technologies have received new development, and multidisciplinary scientific research is being conducted regarding the regenerative abilities of the liver.

Self-assembling peptide hydrogel scaffold integrating stem cell-derived exosomes for infected bone defects

Infected bone defect (IBD) is a great challenge in orthopedics, which involves in bone loss and infection. Here, a self-assembling hydrogel scaffold (named AMP-RAD/EXO), integrating antimicrobial peptides(AMPs), RADA16 and BMSCs exosomes with an innovative strategy, is developed and applied in IBD treatment for sustained antimicrobial ability, accelerating osteoblasts proliferation and promoting bone regeneration. AMPs present an excellent ability to inhibit infection, RADA16 is a self-assembling peptide hydrogel for AMPs delivery, and BMSCs exosomes can promote the bone regeneration. The prepared AMP-RAD/EXO exhibited a polyporous 3D structure for imbibition of BMSCs exosomes and migration of osteoblasts. In vitro studies indicate AMP-RAD/EXO can inhibit the growth of Staphylococcus aureus, accelerate the proliferation and migration of BMSCs. More importantly, in vivo results also prove that AMP-RAD/EXO exhibit an excellent effect on IBD treatment. Thus, the prepared AMP-RAD/EXO provides a multifunctional scaffold concept for bone tissue engineering technology.

3D Bioprinting-Based Dopamine-Coupled Flexible Material for Nasal Cartilage Repair.

Since 3D printing can be used to design implants according to the specific conditions of patients, it has become an emerging technology in tissue engineering and regenerative medicine. How to improve the mechanical, elastic and adhesion properties of 3D-printed photocrosslinked hydrogels is the focus of cartilage tissue repair and reconstruction research. We established a strategy for toughening hydrogels by mixing GelMA-DOPA (GD), which is prepared by coupling dopamine (DA) with GelMA, with HAMA, bacterial cellulose (BC) to produce composite hydrogels (HB-GD). HB-GD hydrogel scaffolds were characterized in vitro by scanning electron microscopy (SEM), Young's modulus, swelling property and rheological property tests. And biocompatibility and chondrogenic ability were tested by live/dead staining, DNA quantitative analysis and immunofluorescence staining. Combined with 3D bioprinting technology, mouse chondrocytes (ADTC5) were added to form a biological chain to construct an in vitro model, and the feasibility of the model for nasal cartilage regeneration was verified by cytology evaluation. With the increase of GD concentration, the toughness of the composite hydrogel increased (47.0 ± 2.7 kPa (HB-5GD)-158 ± 3.2 kPa (HB-20GD)), and it had excellent swelling properties, rheological properties and printing properties. The HB-GD composite hydrogel promoted the proliferation and differentiation of ATDC5. Cells in 3D printed scaffolds had higher survival rates (> 95%) and better protein expression than the encapsulated cultures. The HB-10GD hydrogel can be made into a porous scaffold with precise shape, good internal pore structure, high mechanical strength and good swelling rate through extrusion 3D printing. This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Three-Dimensional-Printed Spherical Hollow Structural Scaffolds for Guiding Critical-Sized Bone Regeneration.

The treatment of bone tissue defects continues to be a complex medical issue. Recently, three-dimensional (3D)-printed scaffold technology for bone tissue engineering (BTE) has emerged as an important therapeutic approach for bone defect repair. Despite the potential of BTE scaffolds to contribute to long-term bone reconstruction, there are certain challenges associated with it including the impediment of bone growth within the scaffolds and vascular infiltration. These difficulties can be resolved by using scaffold structural modification strategies that can effectively guide bone regeneration. This study involved the preparation of biphasic calcium phosphate spherical hollow structural scaffolds (SHSS) with varying pore sizes using 3D printing (photopolymerized via digital light processing). The chemical compositions, microscopic morphologies, mechanical properties, biocompatibilities, osteogenic properties, and impact on repairing critical-sized bone defects of SHSS were assessed through characterization analyses, in vitro cytological assays, and in vivo biological experiments. The results revealed the biomimetic properties of SHSS and their favorable biocompatibility. The scaffolds stimulated cell adhesion, proliferation, differentiation, and migration and facilitated the expression of osteogenic genes and proteins, including Col-1, OCN, and OPN. Furthermore, they could effectively repair a critical-sized bone defect in a rabbit femoral condyle by establishing an osteogenic platform and guiding bone regeneration in the defect region. This innovative strategy presents a novel therapeutic approach for assessing critical-sized bone defects.

Squid as a Model Organism - Part 2: Biomedical and Tissue Engineering Technologies of Skin

Nature has always been the greatest teacher for humans, and many of our inventions have been inspired by a careful examination of natural phenomena. Even today, despite significant advancements in technology, scientists continue to turn to nature to find solutions to problems and enhance various systems. Discovering the complex mechanisms within the bodies of living organisms has consistently provided a foundation for numerous ideas and innovations. The colossal squid, with its unique characteristics, has recently garnered the attention of many scientists, serving as a source of inspiration for diverse medical and engineering designs. In this study, we will focus on the squid’s skin and its camouflage mechanisms, highlighting how humanity has leveraged this remarkable creature for scientific, and engineering progress.
  
 Keywords: squid, nature-inspired, biotechnology, biological and engineering technologies

Transplantation of Neural Stem Cells Loaded in an IGF-1 Bioactive Supramolecular Nanofiber Hydrogel for the Effective Treatment of Spinal Cord Injury.

Spinal cord injury (SCI) leads to massive cell death, disruption, and demyelination of axons, resulting in permanent motor and sensory dysfunctions. Stem cell transplantation is a promising therapy for SCI. However, owing to the poor microenvironment that develops following SCI, the bioactivities of these grafted stem cells are limited. Cell implantation combined with biomaterial therapies is widely studied for the development of tissue engineering technology. Herein, an insulin-like growth factor-1 (IGF-1)-bioactive supramolecular nanofiber hydrogel (IGF-1 gel) is synthesized that can activate IGF-1 downstream signaling, prevent the apoptosis of neural stem cells (NSCs), improve their proliferation, and induce their differentiation into neurons and oligodendrocytes. Moreover, implantation of NSCs carried out with IGF-1 gels promotes neurite outgrowth and myelin sheath regeneration at lesion sites following SCI. In addition, IGF-1 gels can enrich extracellular vesicles (EVs) derived from NSCs or from nerve cells differentiated from these NSCs via miRNAs related to axonal regeneration and remyelination, even in an inflammatory environment. These EVs are taken up by autologous endogenous NSCs and regulate their differentiation. This study provides adequate evidence that combined treatment with NSCs and IGF-1 gels is a potential therapeutic strategy for treating SCI.

Ultrasound Tissue Engineering Technology for Regulating Immune Microenvironment

AbstractThe immune microenvironment is critical for the occurrence, progression, and treatment of diseases. Ultrasound tissue engineering technology utilizes ultrasound and the principles of tissue engineering to repair, regenerate, and functionally reconstruct biological tissues. Ultrasound therapy is a non‐invasive treatment modality that regulates the immune microenvironment and maintains homeostasis through various characteristic effects. Ultrasound‐responsive biomaterials utilize biological properties or drug/gene delivery to regulate the immune microenvironment under ultrasound stimulation for targeted and purposeful treatment. This article comprehensively and systematically reviews advancements in ultrasound tissue engineering technology for regulating the immune microenvironment. First, the changes in the immune microenvironment at different stages of the disease is briefly illustrated. It is then reviewed the regulation of the immune microenvironment by ultrasound and ultrasound‐responsive biomaterials in five types of diseases: tumor, cardiovascular system diseases, nervous system diseases, musculoskeletal diseases, and wound. Finally, the prospects of the ultrasound tissue engineering technology for regulating the immune microenvironment is summarized.

Комбинированные матрицы и тканевые инженерные конструкции из биополимеров в реконструктивно-восстановительной хирургии ЛОР-органов

Microtia is a combined congenital malformation with the prevalence of one case per 10,000–15,000 newborns, which accounts for 50% of all congenital malformations. Treatment of microtia is a challenging task. Numerous solutions have been proposed, however, none of these options guarantee good functional and aesthetic outcome. High hopes for solving the problem are placed on advances in reconstructive surgery. The study was aimed to determine the possibility of using advanced biocompatible endoprostheses manufactured using the tissue engineering technologies. Two closely related male 2-year-old minipigs of the Sus salvanius breed underwent implantation of bioengineered implants manufactured by combined 3D bioprinting with application of the collagen solution containing autologous cartilage tissue cells under the temporal fascia. The samples were collected 3 months later. Histological examination and immunohistochemistry showed that the implanted endoprosthesis initiated the development of regenerated connective tissue and its own vasculature in 100% of cases, thereby ensuring cell viability and integrity of biological structures; furthermore, no facts of the endoprosthesis rejection or resorption were reported. We have concluded that the developed implant manufacturing method is promising and can provide the basis for creation of domestic porous ear implants based on biocompatible polymeric materials, hydrogels, and autologous cellular material. It is necessary to further test the auricular implant using biological models.

Bibliometric and Visualization Analysis of Stem Cell Therapy for Erectile Dysfunction.

As a common male disease, erectile dysfunction (ED) seriously affects the physical and mental health of patients. In recent years, studies have continued to point out the great potential of stem cell therapy (SCT) in the treatment of ED. The purpose of this study is to comprehensively analyze the research of SCT for ED and understand the development trends and research frontiers in this field. Publications regarding SCT and ED were retrieved and collected from the Web of Science Core Collection. CiteSpace and VOSviewer software were then utilized for bibliometric and visualization analysis. A total of 524 publications were eventually included in this study. The annual number of publications in this field was increasing year by year. China and the USA were the two most productive countries. Lin GT, Lue TF and Lin CS, and the University of California San Francisco where they worked were the most productive research group and institution, respectively. The journal with the largest number of publications was The Journal of Sexual Medicine, and the following were mostly professional journals of urology and andrology. Diabetes mellitus-induced ED and cavernous nerve injury-related ED were the two most commonly constructed models of ED in studies. Concerning the types of stem cells, mesenchymal stem cells derived from adipose and bone marrow were most frequently used. Moreover, future research would mainly focus on exosomes, tissue engineering technology, extracorporeal shockwave therapy, and clinical translation. The research of SCT for ED will receive increasing global attention in the future. Our study provided bibliometric and visualization analysis of published literature, helping researchers understand the global landscape and frontiers in this field. More preclinical and clinical studies should be conducted to more deeply explore the underlying mechanisms of treatment and promote clinical translation.

Biomimetic fabrication of sr-silk fibroin co-assembly hydroxyapatite based microspheres with angiogenic and osteogenic properties for bone tissue engineering

Bone defects caused by trauma, tumor resection, or developmental abnormalities are important issues in clinical practice. The vigorous development of tissue engineering technology provides new ideas and directions for regenerating bone defects. Hydroxyapatite (HAp), a bioactive ceramic, is extensively used in bone tissue engineering because of its excellent osteoinductive performance. However, its application is challenged by its single function and conventional environment-unfriendly synthesis methods. In this study, we successfully "green" synthesized sr-silk fibroin co-assembly hydroxyapatite nanoparticles (Sr-SF-HA) using silk fibroin (SF) as a biomineralized template, thus enabling it to have angiogenic activity and achieving the combination of organic and inorganic substances. Then, the rough composite microspheres loaded with Sr-SF-HA (CS/Sr-SF-HA) through electrostatic spraying technology and freeze-drying method were prepared. The CCK-8 test and live/dead cell staining showed excellent biocompatibility of CS/Sr-SF-HA. Alkaline phosphatase (ALP) staining, alizarin red staining (ARS), immunofluorescence, western blotting, and qRT-PCR test showed that CS/Sr-SF-HA activated the expression of related genes and proteins, thus inducing the osteogenic differentiation of rBMSCs. Moreover, tube formation experiments, scratch experiments, immunofluorescence, and qRT-PCR detection indicated that CS/Sr-SF-HA have good angiogenic activity. Furthermore, in vivo studies showed that the CS/Sr-SF-HA possesses excellent biocompatibility, vascular activity, as well as ectopic osteogenic ability in the subcutaneous pocket of rats. This study indicates that the construction of CS/Sr-SF-HA with angiogenic and osteogenic properties has great potential for bone tissue engineering.

There and Back Again: Building Systems That Integrate, Interface, and Interact with the Human Body.

Since Dr. Theodor Schwann posed the extension of Cell Theory to mammals in 1839, scientists have dreamt up ways to interface with and influence the cells. Recently, considerable ground in this area is gained, particularly in the scope of bioelectronics. New advances in this area have provided with a means to record electrical activity from cells, examining neural firing or epithelial barrier integrity, and stimulate cells through applied electrical fields. Many of these applications utilize invasive implantation systems to perform this interaction in close proximity to the cells in question. Traditionally, the body's immune system fights back against these systems through the foreign body response, limiting the efficacy of long-term interactions. New technologies in tissue engineering, biomaterials science, and bioelectronics offer the potential to circumvent the foreign body response and create stable long-term biological interfaces. Looking ahead, the next advancements in the biomedical sciences cantruly integrate, interface, and interact with the human body.

Calcium Phosphate Biomaterials for 3D Bioprinting in Bone Tissue Engineering.

Three-dimensional bioprinting is a promising technology for bone tissue engineering. However, most hydrogel bioinks lack the mechanical and post-printing fidelity properties suitable for such hard tissue regeneration. To overcome these weak properties, calcium phosphates can be employed in a bioink to compensate for the lack of certain characteristics. Further, the extracellular matrix of natural bone contains this mineral, resulting in its structural robustness. Thus, calcium phosphates are necessary components of bioink for bone tissue engineering. This review paper examines different recently explored calcium phosphates, as a component of potential bioinks, for the biological, mechanical and structural properties required of 3D bioprinted scaffolds, exploring their distinctive properties that render them favorable biomaterials for bone tissue engineering. The discussion encompasses recent applications and adaptations of 3D-printed scaffolds built with calcium phosphates, delving into the scientific reasons behind the prevalence of certain types of calcium phosphates over others. Additionally, this paper elucidates their interactions with polymer hydrogels for 3D bioprinting applications. Overall, the current status of calcium phosphate/hydrogel bioinks for 3D bioprinting in bone tissue engineering has been investigated.

Addressing the structural sophistication of meat via plant-based tissue engineering

The escalating environmental impact of traditional livestock farming, particularly beef production, has spurred the search for sustainable meat alternatives. This study introduces a novel Plant-Based Tissue Engineering (PBTE) approach, to replicate the complex structure and sensory experience of whole-muscle cuts of meat using plant-based ingredients. Leveraging principles of tissue engineering and advanced food manufacturing technologies, PBTE deconstructs meat into its fundamental components: muscle, fat, and connective tissue, and reconstructs them using a combination of plant proteins, fats and polysaccharide materials. The muscle component is reassembled to mimic the anisotropic fibrous structure of beef, while the fat component is engineered through lipid encapsulation within a hydrocolloid matrix. Advanced manufacturing techniques, including additive manufacturing and robotics, are utilized for precise spatial configuration and assembly of these components. Our findings demonstrate that PBTE can effectively replicate the mechanical integrity, texture, and sensory attributes of traditional meat, presenting a promising alternative that could significantly reduce the environmental footprint of meat production. This approach aligns with the principles of Soft Matter in the manipulation of artificial structures and materials for mimicking naturally occurring designs, such as whole cut meat foods. It also holds substantial potential for revolutionizing the alternative protein industry by catering to a broader consumer base, including flexitarians and meat-eaters.

An injectable and photocurable methacrylate-silk fibroin/nano-hydroxyapatite hydrogel for bone regeneration through osteoimmunomodulation

Tissue engineering has emerged as a promising approach for addressing bone defects. Most of the traditional 3D printing materials predominantly relying on polymers and ceramics. Although these materials exhibit superior osteogenic effects, their gradual degradation poses a limitation. Digital light processing (DLP) 3D bioprinting that uses natural biomaterials as bioinks has become one of the promising strategies for bone regeneration. In this study, we introduce a hydrogel biomaterial derived from silk fibroin (SF). Notably, we present the novel integration of nano-hydroxyapatite (nHA) into the hydrogel, forming a composite hydrogel that rapidly cross-links upon initiation. Moreover, we demonstrate the loading of nHA through non-covalent bonds in SilMA. In vitro experiments reveal that composite hydrogel scaffolds with 10 % nHA exhibit enhanced osteogenic effects. Transcriptomic analysis indicates that the composite hydrogel promotes bone regeneration by inducing M2 macrophage polarization. Furthermore, rat femoral defect experiments validate the efficacy of SilMA/nHA10 in bone regeneration. This study synthesis of a simple and effective composite hydrogel bioink for bone regeneration, presenting a novel strategy for the future implementation of digital 3D printing technology in bone tissue engineering.

Advancements in preclinical human-relevant modeling of pulmonary vasculature on-chip

Preclinical human-relevant modeling of organ-specific vasculature offers a unique opportunity to recreate pathophysiological intercellular, tissue-tissue, and cell-matrix interactions for a broad range of applications. Lung vasculature is particularly important due to its involvement in genesis and progression of rare, debilitating disorders as well as common chronic pathologies. Here, we provide an overview of the latest advances in the development of pulmonary vascular (PV) models using emerging microfluidic tissue engineering technology Organs-on-Chips (so-called PV-Chips). We first review the currently reported PV-Chip systems and their key features, and then critically discuss their major limitations in reproducing in vivo-seen and disease-relevant cellularity, localization, and microstructure. We conclude by presenting latest efforts to overcome such technical and biological limitations and future directions.

Tissue engineering application on coronavirus (Covid-19) Pandemic: A review

Background: The use of biomaterials in diagnosing and treating COVID-19 has been investigated in various forms and origins, including natural and synthetic materials. The development of rapid and highly sensitive biosensors based on field-effect transistors and the creation of antiviral platforms, vaccines, and nanomaterials have been the focus of most research on the application of biomaterials. Tissue engineering encompasses the study of tissue development, behavior, and growth factors that are more readily supported in the medical setting. This paper reviews the roles of biomaterials, tissue engineering, drug delivery, microfluidics, and 3D printing technologies in urgently responding to pandemics like COVID-19. In addition, this research covers a broad area of vaccines and treatments, reviewing the most promising candidate drugs and vaccines that have entered clinical trials to date. These engineering methods focus on biomaterials, drug delivery systems, and replacing damaged tissues and organs. Some biodegradable biomaterials, such as chitosan, mesoporous silica rods, and PLGA nanoparticles, have been utilized as vaccine platforms and can be employed in developing a SARS-CoV-2 vaccine. Notably, the proposed platform's size, shape, and other physicochemical characteristics should be carefully planned to achieve the desired effects on the immune system. Conclusion: Tissue engineers possess unique tools that can significantly advance our understanding of viral illnesses and aid in creating diagnostic and therapeutic platforms. Future research on COVID-19 infection and drug testing will benefit significantly from developing organ-on-a-chip technologies. Developing innovative biomaterial-based techniques for preventing, treating, and monitoring COVID-19 requires collaboration across multiple disciplines.

Biomaterials-Based Antioxidant Strategies for the Treatment of Oxidative Stress Diseases.

Oxidative stress is characterized by an increase in reactive oxygen species or a decrease in antioxidants in the body. This imbalance leads to detrimental effects, including inflammation and multiple chronic diseases, ranging from impaired wound healing to highly impacting pathologies in the neural and cardiovascular systems, or the bone, amongst others. However, supplying compounds with antioxidant activity is hampered by their low bioavailability. The development of biomaterials with antioxidant capacity is poised to overcome this roadblock. Moreover, in the treatment of chronic inflammation, material-based strategies would allow the controlled and targeted release of antioxidants into the affected tissue. In this review, we revise the main causes and effects of oxidative stress, and survey antioxidant biomaterials used for the treatment of chronic wounds, neurodegenerative diseases, cardiovascular diseases (focusing on cardiac infarction, myocardial ischemia-reperfusion injury and atherosclerosis) and osteoporosis. We anticipate that these developments will lead to the emergence of new technologies for tissue engineering, control of oxidative stress and prevention of diseases associated with oxidative stress.

BONE TISSUE REGENERATION INDUCED BY LOCAL DELIVERY OF BONE MORPHOGENETIC PROTEIN 2 FROM PRO-ANGIOGENIC NEAR-INFRARED-RESPONSIVE HYDROGELS

In this work, we combined tissue engineering and gene therapy technologies to develop a therapeutic platform for bone regeneration. We have developed photothermal fibrin-based hydrogels that incorporate degradable CuS nanoparticles (CuSNP) which transduce incident near-infrared (NIR) light into heat. A heat-activated and rapamycin-dependent transgene expression system was incorporated into mesenchymal stem cells to conditionally control the production of bone morphogenetic protein 2 (BMP-2). Genetically engineered cells were entrapped in the photothermal hydrogels. In the presence of rapamycin, photoinduced mild hyperthermia induced the release of BMP-2 from the NIR responsive cell constructs. Transcriptome analysis of BMP-2 expressing cells showed a signature of induced genes related to stem cell proliferation and angiogenesis. We next generated 4 mm diameter calvarial defects in the left parietal bone of immunocompetent mice. The defects were filled with NIR-responsive hydrogels entrapping cells that expressed BMP-2 under the control of the gene circuit. After one and eight days, rapamycin was administered intraperitoneally followed by irradiation with an NIR laser. Ten weeks after implantation, the animals were euthanized and samples from the bone defect zone were processed for histological analysis using Masson's trichrome staining and for immunohistochemistry analyses using specific CD31 and CD105 antibodies. Samples from mice that were only administered rapamycin or vehicle or that were only NIR-irradiated showed the persistence of fibrous tissue bridging the defect. In animals that were treated with rapamycin, NIR irradiation of implants resulted in the formation of new mineralized tissue with a high degree of vascularization, thus indicating the therapeutic potential of the approach.Acknowledgements: This research was supported by grants RTI2018-095159-B-I00 and PID2021-126325OB-I00 (MCIN/AEI/10.13039/501100011033 and “ERDF A way of making Europe”), by grant P2022/BMD- 7406 (Regional Government of Madrid). M.A.L-J. is the recipient of predoctoral fellowship PRE2019-090430 (MCIN/AEI/10.13039/501100011033).