METTL3 promotes oxaliplatin resistance of gastric cancer CD133+ stem cells by promoting PARP1 mRNA stability.

Oxaliplatin is the first-line regime for advanced gastric cancer treatment, while its resistance is a major problem that leads to the failure of clinical treatments. Tumor cell heterogeneity has been considered as one of the main causes for drug resistance in cancer. In this study, the mechanism of oxaliplatin resistance was investigated through in vitro human gastric cancer organoids and gastric cancer oxaliplatin-resistant cell lines and in vivo subcutaneous tumorigenicity experiments. The in vitro and in vivo results indicated that CD133+ stem cell-like cells are the main subpopulation and PARP1 is the central gene mediating oxaliplatin resistance in gastric cancer. It was found that PARP1 can effectively repair DNA damage caused by oxaliplatin by means of mediating the opening of base excision repair pathway, leading to the occurrence of drug resistance. The CD133+ stem cells also exhibited upregulated expression of N6-methyladenosine (m6A) mRNA and its writer METTL3 as showed by immunoprecipitation followed by sequencing and transcriptome analysis. METTTL3 enhances the stability of PARP1 by recruiting YTHDF1 to target the 3'-untranslated Region (3'-UTR) of PARP1 mRNA. The CD133+ tumor stem cells can regulate the stability and expression of m6A to PARP1 through METTL3, and thus exerting the PARP1-mediated DNA damage repair ability. Therefore, our study demonstrated that m6A Methyltransferase METTL3 facilitates oxaliplatin resistance in CD133+ gastric cancer stem cells by Promoting PARP1 mRNA stability which increases base excision repair pathway activity.

Integration of polyurethane meniscus scaffold during ACL revision is not reliable at 5 years despite favourable clinical outcome.

PURPOSE: The aim of this study was to evaluate the clinical outcome at 5-year follow-up of a one-step procedure combining anterior cruciate ligament (ACL) reconstruction and partial meniscus replacement using a polyurethane scaffold for the treatment of symptomatic patients with previously failed ACL reconstruction and partial medial meniscectomy. Moreover, the implanted scaffolds have been evaluated by MRI protocol in terms of morphology, volume, and signal intensity. METHODS: Twenty patients with symptomatic knee laxity after failed ACL reconstruction and partial medial meniscectomy underwent ACL revision combined with polyurethane-based meniscal scaffold implant. Clinical assessment at 2- and 5-year follow-ups included VAS, Tegner Activity Score, International Knee Documentation Committee (IKDC), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and the Lysholm Score. MRI evaluation of the scaffold was performed according to the Genovese scale with quantification of the scaffold's volume at 1- and 5-year follow-ups. RESULTS: All scores revealed clinical improvement as compared with the preoperative values at the 2- and 5-year follow-ups. However, a slight, but significant reduction of scores was observed between 2 and 5 years. Concerning the MRI assessment, a significant reduction of the scaffold's volume was observed between 1 and 5 years. Genovese Morphology classification at 5 years included two complete resorptions (Type 3) and all the remaining patients had irregular morphology (Type 2). With regard to the Genovese Signal at the 5-year follow-up, three were classified as markedly hyperintense (Type 1), 15 as slightly hyperintense (Type 2), and two as isointense (Type 1). CONCLUSION: Simultaneous ACL reconstruction and partial meniscus replacement using a polyurethane scaffold provides favourable clinical outcomes in the treatment of symptomatic patients with previously failed ACL reconstruction and partial medial meniscectomy at 5 years. However, MRI evaluation suggests that integration of the scaffold is not consistent. LEVEL OF EVIDENCE: Level IV.

Manganese-Labeled Alginate Hydrogels for Image-Guided Cell Transplantation.

Cell transplantation has been studied extensively as a therapeutic strategy for neurological disorders. However, to date, its effectiveness remains unsatisfactory due to low precision and efficacy of cell delivery; poor survival of transplanted cells; and inadequate monitoring of their fate in vivo. Fortunately, different bio-scaffolds have been proposed as cell carriers to improve the accuracy of cell delivery, survival, differentiation, and controlled release of embedded stem cells. The goal of our study was to establish hydrogel scaffolds suitable for stem cell delivery that also allow non-invasive magnetic resonance imaging (MRI). We focused on alginate-based hydrogels due to their natural origin, biocompatibility, resemblance to the extracellular matrix, and easy manipulation of gelation processes. We optimized the properties of alginate-based hydrogels, turning them into suitable carriers for transplanted cells. Human adipose-derived stem cells embedded in these hydrogels survived for at least 14 days in vitro. Alginate-based hydrogels were also modified successfully to allow their injectability via a needle. Finally, supplementing alginate hydrogels with Mn ions or Mn nanoparticles allowed for their visualization in vivo using manganese-enhanced MRI. We demonstrated that modified alginate-based hydrogels can support therapeutic cells as MRI-detectable matrices.

Hydrogels in the treatment of rheumatoid arthritis: drug delivery systems and artificial matrices for dynamic in vitro models.

Rheumatoid arthritis (RA) is an autoimmune and chronic inflammatory disorder that mostly affects the synovial joints and can promote both cartilage and bone tissue destruction. Several conservative treatments are available to relieve pain and control the inflammation; however, traditional drugs administration are not fully effective and present severe undesired side effects. Hydrogels are a very attractive platform as a drug delivery system to guarantee these handicaps are reduced, and the therapeutic effect from the drugs is maximized. Furthermore, hydrogels can mimic the physiological microenvironment and have the mechanical behavior needed for use as cartilage in vitro model. The testing of these advanced delivery systems is still bound to animal disease models that have shown low predictability. Alternatively, hydrogel-based human dynamic in vitro systems can be used to model diseases, bypassing some of the animal testing problems. RA dynamic disease models are still in an embryonary stage since advances regarding healthy and inflamed cartilage models are currently giving the first steps regarding complexity increase. Herein, recent studies using hydrogels in the treatment of RA, featuring different hydrogel formulations are discussed. Besides, their use as artificial extracellular matrices in dynamic in vitro articular cartilage is also reviewed.

Exosome mediated transfer of miRNA-140 promotes enhanced chondrogenic differentiation of bone marrow stem cells for enhanced cartilage repair and regeneration.

Exosomes (EXs) are nanocarrier vesicles with 20-50 nm dimensions. They are involved in cell proliferation and differentiation and in protecting the integrity of materials. They can be isolated from plasma and immunoreactive components. Recent studies demonstrated their potential role in cartilage regeneration. To enhance their regenerative effect, molecules like microRNA (miR-140) can be loaded in EX that acts as RNA delivery systems. In this study, we combined EX with miR-140 to enhance cell differentiation by inducing membrane fusion and consequent miRNA released into the cytoplasm. The carrier RNA complex was successfully synthesized through freeze and thaw method leading to the formation of EX-containing miR-140. The EX morphology was assessed through transmission electron microscopy and their miR-140 uptake efficiency through real-time polymerase chain reaction (RT-PCR). The effects on bone marrow stem cells (BMSCs) were evaluated by in vitro cell culture. Cell adhesion and morphology were studied using a bio-scanning electron microscope and confocal laser scanning microscope. Differentiation BMSCs into chondrocytes was analyzed by RT-PCR and histology. Our results confirm the bioactive role of EX loaded with miR-140 in the differentiation of BMSCs into chondrocytes. EXs were biocompatible involving in the cartilage healing process through chromogenic differentiation of BMCS exploiting the tissue engineering route.

The Meniscus in Normal and Osteoarthritic Tissues: Facing the Structure Property Challenges and Current Treatment Trends.

The treatment of meniscus injuries has recently been facing a paradigm shift toward the field of tissue engineering, with the aim of regenerating damaged and diseased menisci as opposed to current treatment techniques. This review focuses on the structure and mechanics associated with the meniscus. The meniscus is defined in terms of its biological structure and composition. Biomechanics of the meniscus are discussed in detail, as an understanding of the mechanics is fundamental for the development of new meniscal treatment strategies. Key meniscal characteristics such as biological function, damage (tears), and disease are critically analyzed. The latest technologies behind meniscal repair and regeneration are assessed.

Finding the perfect match between nanoparticles and microfluidics to respond to cancer challenges.

The clinical translation of new cancer theranostic has been delayed by inherent cancer's heterogeneity. Additionally, this delay has been enhanced by the lack of an appropriate in vitro model, capable to produce accurate data. Nanoparticles and microfluidic devices have been used to obtain new and more efficient strategies to tackle cancer challenges. On one hand, nanoparticles-based therapeutics can be modified to target specific cells, and/or molecules, and/or modified with drugs, releasing them over time. On the other hand, microfluidic devices allow the exhibition of physiologically complex systems, incorporation of controlled flow, and control of the chemical environment. Herein, we review the use of nanoparticles and microfluidic devices to address different cancer challenges, such as detection of CTCs and biomarkers, point-of-care devices for early diagnosis and improvement of therapies. The future perspectives of cancer challenges are also addressed herein.

Fundamentals and Current Strategies for Peripheral Nerve Repair and Regeneration.

A body of evidence indicates that peripheral nerves have an extraordinary yet limited capacity to regenerate after an injury. Peripheral nerve injuries have confounded professionals in this field, from neuroscientists to neurologists, plastic surgeons, and the scientific community. Despite all the efforts, full functional recovery is still seldom. The inadequate results attained with the "gold standard" autograft procedure still encourage a dynamic and energetic research around the world for establishing good performing tissue-engineered alternative grafts. Resourcing to nerve guidance conduits, a variety of methods have been experimentally used to bridge peripheral nerve gaps of limited size, up to 30-40 mm in length, in humans. Herein, we aim to summarize the fundamentals related to peripheral nerve anatomy and overview the challenges and scientific evidences related to peripheral nerve injury and repair mechanisms. The most relevant reports dealing with the use of both synthetic and natural-based biomaterials used in tissue engineering strategies when treatment of nerve injuries is envisioned are also discussed in depth, along with the state-of-the-art approaches in this field.

Microfluidic Devices and Three Dimensional-Printing Strategies for in vitro Models of Bone.

Bone is a complex and highly dynamic tissue, which has been worldwide studied, from fundamental biology to tissue engineering fields. Even so, current in vitro models do not truly replicate the native bone tissue environment. For so, new and improved in vitro tissue models are necessary to obtain more reliable data, not only in a development point of view, but also to fasten the translation of new drugs into the clinics. In this reasoning, tissue-engineering strategies were applied to develop mimetic and three-dimensional (3D) microenvironments, which were associated with microfluidic devices for the development of more complex and realistic systems. Such devices mimic blood vessels that are present in the native tissue, thus enabling the study of complex biological mechanism as such as bone angiogenesis. More recently, 3D printing has been pursued to produce more intricate microfluidic devices and engineered tissues in a single step. The ability to print spatially controlled structures composed of different biomaterials, growth factors and cells caught the attention of scientists for the development of more efficient in vitro models. Additionally, it allows obtaining microfluidic devices and/or engineered tissues with the desired architecture within a small amount of time and with reduced costs. Recently, the use of high-resolution scanning boosted the production of patient-specific implants. Despite the difficulties associated with 3D printed structures that still need to be overcome, it has been proven to be a valuable tool to accomplish a new generation of 3D bioprinted bone-on-a-chip platforms.

Biomaterials and Microfluidics for Liver Models.

Over the past years, important progresses have been made in the field of tissue engineering. Many of the early trials to improve the development of an engineered tissue construct were centered on the concept of seeding cells onto biomaterial scaffold. By means of innovative manufacturing machineries, the conception of a preformed scaffold became possible. Nowadays, several tissue engineering challenges are associated with applying this scaffold technology to one vital organ construct: liver. The development of microscale tissue ("micro-tissue") constructs to mimic partially the complex structure-function interactions of liver parenchyma have been obtained through the engineering of sophisticated biomaterial scaffolds, liver-cell sources, and in vitro culture techniques. For in vitro applications, micro-tissue constructs are being upgraded into cell-based assays for testing acute, chronic and idiosyncratic toxicities of drugs or pathogens. The present chapter will focus on the biomaterials currently used for the development of in vitro liver constructs as well as the description of the microfluidic-based models that show great promise for liver regenerative medicine approaches.

Microfluidics for Angiogenesis Research.

Angiogenesis is a natural and vital phenomenon of neovascularization that occurs from pre-existing vasculature, being present in many physiological processes, namely in development, reproduction and regeneration. Being a highly dynamic and tightly regulated process, its abnormal expression can be on the basis of several pathologies. For that reason, angiogenesis has been a subject of major interest among the scientific community, being transverse to different areas and founding particular attention in tissue engineering and cancer research fields. Microfluidics has emerged as a powerful tool for modelling this phenomenon, thereby surpassing the limitations associated to conventional angiogenic models. Holding a tremendous flexibility in terms of experimental design towards a specific goal, microfluidic systems can offer an unlimited number of opportunities for investigating angiogenesis in many relevant scenarios, namely from its fundamental comprehension in normal physiological processes to the identification and testing of new therapeutic targets involved on pathological angiogenesis. Additionally, microvascular 3D in vitro models are now opening up new prospects in different fields, being used for investigating and establishing guidelines for the development of next generation of 3D functional vascularized grafts. The promising applications of this emerging technology in angiogenesis studies are herein overviewed, encompassing fundamental and applied research.

Biomaterials and Microfluidics for Drug Discovery and Development.

Microfluidic devices are now one of the most promising tools to mimic in vivo like conditions, either in normal or disease scenarios, such as tumorigenesis or pathogenesis. Together with the potential of biomaterials, its combination with microfluidics represents the ability to more closely mimic cells' natural microenvironment concerning its three-dimensional (3D) nature and continuous perfusion with nutrients and cells' crosstalk. Due to miniaturization and increased experimental throughput, microfluidics have generated significant interest in the drug discovery and development domain. Herein, the most recent advances in the field of microfluidics for drug discovery are overviewed, and the role of biomaterials in 3D in vitro models and the contribution of organ-on-a-chip technologies highlighted.

Dynamic Culture Systems and 3D Interfaces Models for Cancer Drugs Testing.

The mass use of biological agents for pharmaceutical purposes started with the development and distribution of vaccines, followed by the industrial production of antibiotics. The use of dynamic systems, such as bioreactors, had been already applied in the food industry in fermentation processes and started being used for the development of pharmaceutical agents from this point on. In the last decades, the use of bioreactors and microfluidic systems has been expanded in different fields. The emergence of the tissue engineering led to the development of in vitro models cultured in dynamic systems. This is particularly relevant considering the urgent reduction of the total dependence on animal disease models that is undermining the development of novel drugs, using alternatively human-based models to make the drug discovery process more reliable. The failure out coming from animal models has been more prevalent in certain types of cancer, such as glioblastoma multiform and in high-grade metastatic cancers like bone metastasis of breast or prostatic cancer. The difficulty in obtaining novel drugs for these purposes is mostly linked to the barriers around the tumors, which these bioactive molecules have to overcome to become effective. For that reason, the individualized study of each interface is paramount and is only realistic once applying human-based samples (e.g. cells or tissues) in three-dimensions for in vitro modeling under dynamic conditions. In this chapter, the most recent approaches to model these interfaces in 3D systems will be explored, highlighting their major contributions to the field. In this section, these systems' impact on increased knowledge in relevant aspects of cancer aggressiveness as invasive or motile cellular capacity, or even resistance to chemotherapeutic agents will have particular focus. The last section of this chapter will focus on the integration of the tumor interfaces in dynamic systems, particularly its application on high-throughput drug screening. The industrial translation of such platforms will be discussed, as well as the main upcoming challenges and future perspectives.

Nanoparticles and Microfluidic Devices in Cancer Research.

Cancer is considered the disease of the century, which can be easily understood considering its increasing incidence worldwide. Over the last years, nanotechnology has been presenting promising theranostic approaches to tackle cancer, as the development of nanoparticle-based therapies. But, regardless of the promising outcomes within in vitro settings, its translation into the clinics has been delayed. One of the main reasons is the lack of an appropriate in vitro model, capable to mimic the true environment of the human body, to test the designed nanoparticles. In fact, most of in vitro models used for the validation of nanoparticle-based therapies do not address adequately the complex barriers that naturally occur in a tumor scenario, as such as blood vessels, the interstitial fluid pressure or the interactions with surrounding cells that can hamper the proper delivery of the nanoparticles into the desired site. In this reasoning, to get a step closer to the in vivo reality, it has been proposed of the use of microfluidic devices. In fact, microfluidic devices can be designed on-demand to exhibit complex structures that mimic tissue/organ-level physiological architectures. Even so, despite microfluidic-based in vitro models do not compare with the reality and complexity of the human body, the most complex systems created up to now have been showing similar results to in vivo animal models. Microfluidic devices have been proven to be a valuable tool to accomplish more realistic tumour's environment. The recent advances in this field, and in particular, the ones enabling the rapid test of new therapies, and show great promise to be translated to the clinics will be overviewed herein.

Scaffolds and coatings for bone regeneration.

Bone tissue has an astonishing self-healing capacity yet only for non-critical size defects (<6 mm) and clinical intervention is needed for critical-size defects and beyond that along with non-union bone fractures and bone defects larger than critical size represent a major healthcare problem. Autografts are, still, being used as preferred to treat large bone defects. Mostly, due to the presence of living differentiated and progenitor cells, its osteogenic, osteoinductive and osteoconductive properties that allow osteogenesis, vascularization, and provide structural support. Bone tissue engineering strategies have been proposed to overcome the limited supply of grafts. Complete and successful bone regeneration can be influenced by several factors namely: the age of the patient, health, gender and is expected that the ideal scaffold for bone regeneration combines factors such as bioactivity and osteoinductivity. The commercially available products have as their main function the replacement of bone. Moreover, scaffolds still present limitations including poor osteointegration and limited vascularization. The introduction of pores in scaffolds are being used to promote the osteointegration as it allows cell and vessel infiltration. Moreover, combinations with growth factors or coatings have been explored as they can improve the osteoconductive and osteoinductive properties of the scaffold. This review focuses on the bone defects treatments and on the research of scaffolds for bone regeneration. Moreover, it summarizes the latest progress in the development of coatings used in bone tissue engineering. Despite the interesting advances which include the development of hybrid scaffolds, there are still important challenges that need to be addressed in order to fasten translation of scaffolds into the clinical scenario. Finally, we must reflect on the main challenges for bone tissue regeneration. There is a need to achieve a proper mechanical properties to bear the load of movements; have a scaffolds with a structure that fit the bone anatomy.

Intersoftware variability impacts classification of cardiac PET exams.

BACKGROUND: Myocardial perfusion imaging (MPI) with 82Rb PET/CT is increasingly utilized in the evaluation of coronary artery disease with high diagnostic accuracy. Various softwares for data processing have been developed over the years with conflicting data regarding their reproducibility. In this study, we compared the quantitative results of myocardial perfusion and exam classification from three different softwares. METHODS: Data from consecutive patients who have undergone rest/stress 82Rb PET/CT MPI at the Royal Brompton & Harefield Trust, London, were analyzed. All data were processed using the Corridor 4DM (Invia, Ann Arbor, Michigan, USA), QPET (Cedars-Sinai, Los Angeles, California, USA), and SyngoMBF (Siemens Healthineers, Erlangen, Germany). The software packages addressed Lortie tracer kinetic model and region of interest (ROI) extraction correction option. STATISTICS: A repeated-measures ANOVA with a Greenhouse-Geisser correction was performed with post hoc tests using Bonferroni correction. For intersoftware variability, Pearson correlation and intraclass correlation coefficients (ICC) were calculated. Bland-Altman assessed limit of agreement. Cohen's Kappa assessed agreement in the classification of exams as normal or abnormal using an MFR cut-off value of 2.0. A P value of less than 0.05 was considered statistically significant. RESULTS: Data from 55 patients were analyzed. The mean values of myocardial blood flow (MBF) and myocardial perfusion reserve (MFR) were statistically significantly different among the softwares (P < 0.05). Corridor4DM had considerably lower values of MFR and classified a more substantial number of exams as abnormal (MFR: 2.21 ± 0.7, 2.4 ± 0.8, and 1.98 ± 0.8; and 18, 15, and 31 exams were abnormal for Syngo, QPET, and Corridor4DM, respectively). Accordingly, kappa agreement was moderate for Syngo vs QPET (k > 0.5), but minimal for Corridor4DM in comparison to its pairs (k < 0.4). CONCLUSION: Users should be cautious when using different software interchangeably as systematic differences amongst them may introduce more extensive quantitative variation which could be clinically significant.

Suturable regenerated silk fibroin scaffold reinforced with 3D-printed polycaprolactone mesh: biomechanical performance and subcutaneous implantation.

The menisci have crucial roles in the knee, chondroprotection being the primary. Meniscus repair or substitution is favored in the clinical management of the meniscus lesions with given indications. The outstanding challenges with the meniscal scaffolds include the required biomechanical behavior and features. Suturability is one of the prerequisites for both implantation and implant survival. Therefore, we proposed herein a novel highly interconnected suturable porous scaffolds from regenerated silk fibroin that is reinforced with 3D-printed polycaprolactone (PCL) mesh in the middle, on the transverse plane to enhance the suture-holding capacity. Results showed that the reinforcement of the silk fibroin scaffolds with the PCL mesh increased the suture retention strength up to 400%, with a decrease in the mean porosity and an increase in crystallinity from 51.9 to 55.6%. The wet compression modulus values were significantly different for silk fibroin, and silk fibroin + PCL mesh by being 0.16 ± 0.02, and 0.40 ± 0.06 MPa, respectively. Both scaffolds had excellent interconnectivity (>99%), and a high water uptake feature (>500%). The tissue's infiltration and formation of new blood vessels were assessed by means of performing an in vivo subcutaneous implantation of the silk fibroin + PCL mesh scaffolds that were seeded with primary human meniscocytes or stem cells. Regarding suturability and in vivo biocompatibility, the findings of this study indicate that the silk fibroin + PCL mesh scaffolds are suitable for further studies to be carried out for meniscus tissue engineering applications such as the studies involving orthotopic meniscal models and fabrication of patient-specific implants.

Thermal annealed silk fibroin membranes for periodontal guided tissue regeneration.

Guided tissue regeneration (GTR) is a surgical procedure applied in the reconstruction of periodontal defects, where an occlusive membrane is used to prevent the fast-growing connective tissue from migrating into the defect. In this work, silk fibroin (SF) membranes were developed for periodontal guided tissue regeneration. Solutions of SF with glycerol (GLY) or polyvinyl alcohol (PVA) where prepared at several weight ratios up to 30%, followed by solvent casting and thermal annealing at 85 °C for periods of 6 and 12 h to produce high flexible and stable membranes. These were characterized in terms of their morphology, physical integrity, chemical structure, mechanical and thermal properties, swelling capability and in vitro degradation behavior. The developed blended membranes exhibited high ductility, which is particular relevant considering the need for physical handling and adaptability to the defect. Moreover, the membranes were cultured with human periodontal ligament fibroblast cells (hPDLs) up to 7 days. Also, the higher hydrophilicity and consequent in vitro proteolytic degradability of these blends was superior to pure silk fibroin membranes. In particular SF/GLY blends demonstrated to support high cell adhesion and viability with an adequate hPDLs' morphology, make them excellent candidates for applications in periodontal regeneration.

Nanocellulose reinforced gellan-gum hydrogels as potential biological substitutes for annulus fibrosus tissue regeneration.

Intervertebral disc (IVD) degeneration is associated with both structural damage and aging related degeneration. Annulus fibrosus (AF) defects such as annular tears, herniation and discectomy require novel tissue engineering strategies to functionally repair AF tissue. An ideal construct will repair the AF by providing physical and biological support, facilitating regeneration. The presented strategy herein proposes a gellan gum-based construct reinforced with cellulose nanocrystals (nCell) as a biological self-gelling AF substitute. Nanocomposite hydrogels were fabricated and characterized with respect to hydrogel swelling capacity, degradation rate in vitro and mechanical properties. Rheological evaluation on the nanocomposites demonstrated the GGMA reinforcement with nCell promoted matrix entanglement with higher scaffold stiffness observed upon ionic crosslinking. Compressive mechanical tests demonstrated compressive modulus values close to those of the human AF tissue. Furthermore, cell culture studies with encapsulated bovine AF cells indicated that nanocomposite constructs promoted cell viability and a physiologically relevant cell morphology for up to fourteen days in vitro.

Biomaterials Developments for Brain Tissue Engineering.

The Central Nervous System (CNS) is a highly complex organ that works as the control centre of the body, managing vital and non-vital functions. Neuro-diseases can lead to the degeneration of neural tissue, breakage of the neuronal networks which can affect vital functions and originate cognitive deficits. The complexity of the neural networks, their components and the low regenerative capacity of the CNS are on the basis for the lack of recovery, having the need for therapies that can promote tissue repair and recovery. Most brain processes are mediated through molecules (e.g. cytokines, neurotransmitters) and cells response accordingly and to surrounding cues, either biological or physical, which offers molecule administration and/or cell transplantation a great potential for use in brain recovery. Biomaterials and in particular, of natural-origin are attractive candidates owed to their intrinsic biological cues and biocompatibility and degradability. Through the use of biomaterials, it is possible to protect the cells/molecules from body clearance, enzymatic degradation while maintaining the components in a place of interest. Moreover, by means of combining several components, it is possible to obtain a more targeted and controlled delivery, to image the biomaterial implantation and its degradation over time and tackling simultaneously occurring events (cell death and inflammation) in brain diseases. In this chapter, it is reviewed some brain-affecting diseases and the current developments on tissue engineering approaches for a functional recovery of the brain from those diseases.