Bioelectric cues from piezoelectric materials in stem-cell adhesion and migration

Intervertebral disc (IVD) degeneration is considered to be the main cause of low back pain (LBP), however, there are lack of long-lasting and effective methods of clinical treatment. Tissue engineering technique based on stem cells be-comes an essential research direction on repair of IVD degeneration at present, and its effectiveness and feasibility have been con-firmed, but it is difficult to maintain the sufficiency and vitality of stem cells in IVD. Previous studies showed that stem cells exist-ed naturally in IVD, and stem cells from stem cell niche could migrate to IVD physiologically to maintain the IVD environment bal-ance under the adverse microenvironment. Unfortunately, these behaviors cannot preclude IVD degeneration. Therefore, theoreti-cal basis for the regeneration of nucleus pulposus (NP) in situ can be obtained from studying the mechanism that the endogenous repair failure during IVD degeneration, the cell death and the migration of stem cells in IVD, and the key regulatory targets to sus-tain the quantity and quality of the stem cells. Although there have been few researches to study the mechanism of the cell death and the migration of stem cells in IVD so far, studies demonstrated that the major inducing factors of IVD degeneration (pressure and hypoxia) could decrease the number of NP cells by autophagy, apoptosis and necroptosis, and chemokines and their receptors played a critical role in the migration of mesenchymal stem cells. These researches provide a clue for studying the mechanism of endogenous repair failure during IVD degeneration. We reviewed the current research situation and progress of the mechanism that endogenous repair failure during IVD degeneration in the following articles. First, we exhibited the potential of IVD stem cells in IVD degeneration repair. Second, the effect of the adverse microenvironment (pressure, hypoxia, etc) on the migration of IVD stem cells was discussed. Third, the mechanism of the stem cell death, autophagy, apoptosis and necroptosis under the adverse (pressure, hypoxia, etc.) microenvironment, and the correlation between the IVD stem cells migration and autophagy, apoptosis and necroptosis was studied. And then tissue engineering of NP was also discussed to achieve the endogenous repair of IVD degenera-tion. These studies will provide an innovative research direction on endogenous repair and a new strategy of early therapy for IVD degeneration.

Poly(3‐hydroxybutyrate) (PHB) has gained significant attention in the realm of medical applications in recent years. This acceptability is rooted in its bioactive properties and remarkable biocompatibility, as the degradation products exhibit negligible cytotoxicity. PHB boasts commendable mechanical resilience, distinguishing it from other polymers commonly used in tissue engineering. Using PHB in fabricating 3D scaffolds serves various objectives, often involving a combination with other polymers, ceramics, fibers, or regenerative factors. This distinctive approach sets it apart, leading to the creation of composite biomaterials. These incorporated materials enhance characteristics such as brittleness, hydrophobicity, degradation rate, and biocompatibility, within the composite. This review delves into the diverse roles that PHB, its alloys, and its compounds play in the engineering of skin, nerve, cartilage, and bone tissues. We explain these roles by highlighting key methodologies for crafting 3D tissue scaffolds with widely adopted techniques, including polymeric sponges, electrospinning, and salt leaching.

Regenerative medicine aims to achieve functional rehabilitation of tissue or cells injured through wound, disease, or aging. Recent findings suggest that nanotechnology provides advanced biomaterials with specified morphologies which can create a nanoscale extracellular environment capable of promoting the adhesion and proliferation of stem cells and accelerating stem cell differentiation in a controlled manner in tissue engineering. This review summarizes the biological effects of nanomaterials and their regenerative medicine applications in orthopedic surgery research, including bone, cartilage, tendons, and nerve tissue engineering.

The effects of LPS on adhesion and migration of human dental pulp stem cells in vitro

In recent years, several studies have reported positive outcomes of cell-based therapies despite insufficient engraftment of transplanted cells. These findings have created a huge interest in the regenerative potential of paracrine factors released from transplanted stem or progenitor cells. Interestingly, this notion has also led scientists to question the role of proteins in the secretome produced by cells, tissues or organisms under certain conditions or at a particular time of regenerative therapy. Further studies have revealed that the secretomes derived from different cell types contain paracrine factors that could help to prevent apoptosis and induce proliferation of cells residing within the tissues of affected organs. This could also facilitate the migration of immune, progenitor and stem cells within the body to the site of inflammation. Of these different paracrine factors present within the secretome, researchers have given proper consideration to stromal cell-derived factor-1 (SDF1) that plays a vital role in tissue-specific migration of the cells needed for regeneration. Recently researchers recognized that SDF1 could facilitate site-specific migration of cells by regulating SDF1-CXCR4 and/or HMGB1-SDF1-CXCR4 pathways which is vital for tissue regeneration. Hence in this study, we have attempted to describe the role of different types of cells within the body in facilitating regeneration while emphasizing the HMGB1-SDF1-CXCR4 pathway that orchestrates the migration of cells to the site where regeneration is needed.

In a large tissue defect, faster migration of adjacent tissue toward the defect shortens the tissue regeneration time. Little has been explored on guiding of directional migration from all fronts of the defect boundary towards the center in tissue engineering. This paper demonstrates the effect of radially aligned fibrous scaffolds (RAFSs) coated with polydopamine in order to guide directional migration of human mesenchymal stem cells (hMSCs). RAFSs were electrospun using a collector with a set of electrodes, each constructed with a metallic ring and a point. The polydopamine was then coated by dipping the scaffolds in a dopamine solution (PD-RAFS). The RAFSs exhibited radial distribution of the fibers from the peripheral region toward the center, and polydopamine was uniformly coated over the entire surface by presenting characteristics of the aromatic ring from dopamine. When hMSCs were seeded on the scaffolds, cells grew in an elongated form toward the center along the fiber direction. In particular, the polydopamine coating improved adhesion and spreading of hMSCs on the scaffolds while preserving initial cell orientation. The hMSCs migrated toward the center of the scaffolds at the border of the seeded area; it was enhanced in the order of PD-RAFS > RAFS > random fibrous scaffolds. Therefore, PD-RAFSs can be utilized as an alternate scaffold that can lead to fast and directional migration of cells for finally facilitating tissue regeneration.

Research of HIF-1 Mediated SDF-1/CXCR4 Axis on the Directional Migration and Neural Differentiation of Mesenchymal Stem Cells

Involvement of SHP2 in focal adhesion, migration and differentiation of neural stem cells

Electrical stimulation is a well-known strategy for regulating cell behavior, both in pathological and physiological processes such as wound healing, tissue regeneration, and embryonic development. Electrotaxis is the directional migration of cells toward the cathode or anode when subjected to electrical stimulation. In this study, we investigated the conditions for enhanced directional migration of electrically stimulated adipose-derived stem cells (ADSCs) during prolonged culture, using a customized agar-salt electrotaxis chamber. Exposure of ADSCs to a 1200 μA electric current for 3 h, followed by cessation of stimulation for 6 h and resumed stimulation for a further 3 h, increased directional cell migration toward the anode without inducing cell death. Moreover, Golgi polarization maintained the direction of polarity parallel to the direction of cell movement. Herein, we demonstrated that a pulsed electric current is sufficient to trigger directional migration of ADSCs in long-term culture while maintaining cell viability.

Osteoarthritis (OA) is a major health problem, characterized by progressive cartilage degeneration. Previous works have shown that mechanical loading can alleviate OA symptoms by suppressing catabolic activities. This study evaluated whether mechanical loading can enhance anabolic activities by facilitating the recruitment of stem cells for chondrogenesis. We evaluated cartilage degradation in a mouse model of OA through histology with H&E and safranin O staining. We also evaluated the migration and chondrogenic ability of stem cells using in vitro assays, including immunohistochemistry, immunofluorescence, and Western blot analysis. The result showed that the OA mice that received mechanical loading exhibited resilience to cartilage damage. Compared to the OA group, mechanical loading promoted the expression of Piezo1 and the migration of stem cells was promoted via the SDF-1/CXCR4 axis. Also, the chondrogenic differentiation was enhanced by the upregulation of SOX9, a transcription factor important for chondrogenesis. Collectively, the results revealed that mechanical loading facilitated cartilage repair by promoting the migration and chondrogenic differentiation of endogenous stem cells. This study provided new insights into the loading-driven engagement of endogenous stem cells and the enhancement of anabolic responses for the treatment of OA.

MCP-1 induces migration of adult neural stem cells

Hematopoietic stem cell transplantation is the most powerful treatment modality for a large number of hematopoietic malignancies, including leukemia. Successful hematopoietic recovery after transplantation depends on homing of hematopoietic stem cells to the bone marrow and subsequent lodging of those cells in specific niches in the bone marrow. Migration of hematopoietic stem cells to the bone marrow is a highly regulated process that requires correct regulation of the expression and activity of various molecules including chemoattractants, selectins and integrins. This review will discuss recent studies that have extended our understanding of the molecular mechanisms underlying adhesion, migration and bone marrow homing of hematopoietic stem cells.

To evaluate the effect of dentine conditioning on migration, adhesion and differentiation of dental pulp stem cells. Dentine discs prepared from extracted human molars were pre-treated with EDTA (10%), NaOCl (5.25%) or H2 O. Migration of dental pulp stem cells towards pre-treated dentine after 24 and 48h was assessed in a modified Boyden chamber assay. Cell adhesion was evaluated indirectly by measuring cell viability. Expression of mineralization-associated genes (COL1A1, ALP, BSP, DSPP, RUNX2) in cells cultured on pre-treated dentine for 7days was determined by RT-qPCR. Nonparametric statistical analysis was performed for cell migration and cell viability data to compare different groups and time-points (Mann-Whitney U-test, α=0.05). Treatment of dentine with H2 O or EDTA allowed for cell attachment, which was prohibited by NaOCl with statistical significance (P=0.000). Furthermore, EDTA conditioning induced cell migration towards dentine. The expression of mineralization-associated genes was increased in dental pulp cells cultured on dentine after EDTA conditioning compared to H2 O-pre-treated dentine discs. EDTA conditioning of dentine promoted the adhesion, migration and differentiation of dental pulp stem cells towards or onto dentine. A pre-treatment with EDTA as the final step of an irrigation protocol for regenerative endodontic procedures has the potential to act favourably on new tissue formation within the root canal.

This review is focused on hybrid polyhydroxyalkanoate-based (PHA) biomaterials with improved physico-mechanical, chemical, and piezoelectric properties and controlled biodegradation rate for applications in bone, cartilage, nerve and skin tissue engineering. PHAs are polyesters produced by a wide range of bacteria under unbalanced growth conditions. They are biodegradable, biocompatible, and piezoelectric polymers, which make them very attractive biomaterials for various biomedical applications. As naturally derived materials, PHAs have been used for multiple cell and tissue engineering applications; however, their widespread biomedical applications are limited due to their lack of toughness, elasticity, hydrophilicity and bioactivity. The chemical structure of PHAs allows them to combine with other polymers or inorganic materials to form hybrid composites with improved structural and functional properties. Their type (films, fibers, and 3D printed scaffolds) and properties can be tailored with fabrication methods and materials used as fillers. Here, we are aiming to fill in a gap in literature, revealing an up-to-date overview of ongoing research strategies that make use of PHAs as versatile and prospective biomaterials. In this work, a systematic and detailed review of works investigating PHA-based hybrid materials with tailored properties and performance for use in tissue engineering applications is carried out. A literature survey revealed that PHA-based composites have better performance for use in tissue regeneration applications than pure PHA.

Platelet concentrates such as platelet-rich plasma, platelet-rich fibrin or concentrated growth factors are cost-effective autologous preparations containing various growth factors, including platelet-derived growth factor, transforming growth factor β, insulin-like growth factor 1 and vascular endothelial growth factor. For this reason, they are often used in regenerative medicine to treat wounds, nerve damage as well as cartilage and bone defects. Unfortunately, after administration, these preparations release growth factors very quickly, which lose their activity rapidly. As a consequence, this results in the need to repeat the therapy, which is associated with additional pain and discomfort for the patient. Recent research shows that combining platelet concentrates with biomaterials overcomes this problem because growth factors are released in a more sustainable manner. Moreover, this concept fits into the latest trends in tissue engineering, which include biomaterials, bioactive factors and cells. Therefore, this review presents the latest literature reports on the properties of biomaterials enriched with platelet concentrates for applications in skin, nerve, cartilage and bone tissue engineering.