Exogenous Growth Factors Research Articles

Self-assembled dodecyl group-modified gelatin microparticle-based hydrogels with angiogenic properties

Supplying oxygen and nutrients to implanted cells or tissues is an important factor that improves their survivability and function in regenerative medicine. Various efforts have been made to develop angiogenic materials by incorporating and releasing growth factors such as vascular endothelial growth factor (VEGF). However, these exogenous growth factors have a short half-life under physiological conditions. We therefore designed a novel angiogenic microparticle (C12-MP) comprising Alaska pollock-derived gelatin (ApGltn) modified with a dodecyl group (C12-ApGltn) to stimulate endogenous VEGF secretion. The C12-MP suspension formed an injectable hydrogel, the rheological properties and enzymatic degradation of which were evaluated. RAW264 cells, mouse macrophage-like cells, cultured with C12-MPs, secreted significantly more VEGF than the original ApGltn MPs. Based on laser Doppler perfusion imaging, the C12-MP hydrogel clearly induced increased blood perfusion in a subcutaneous mouse model compared with the original ApGltn microparticle (Org-MP) or phosphate-buffered saline controls. Histological studies revealed that the areas of nuclear factor (NF)-κB, CD31, and myeloperoxidase staining showed a greater increase at the site injected with C12-MPs than at the site injected with the original ApGltn microparticles or phosphate-buffered saline. The C12-MP hydrogel is a promising angiogenic material for constructing vascular beds for cell transplantation by promoting endogenous VEGF secretion without additional growth factors.

Syndecan -4 and Alkaline Phosphatase Enhancement by Local Application of Exogenous Growth Factors on Traumatic Pulp of Osteoporotic Rats: Immuno-Histochemical Analysis

Syndecan -4 and Alkaline Phosphatase Enhancement by Local Application of Exogenous Growth Factors on Traumatic Pulp of Osteoporotic Rats: Immuno-Histochemical Analysis

Perspectives on Synthetic Materials to Guide Tissue Regeneration for Osteochondral Defect Repair.

Regenerative engineering holds the potential to treat clinically pervasive osteochondral defects (OCDs). In a synthetic materials-guided approach, the scaffold's chemical and physical properties alone instruct cellular behavior in order to effect regeneration, referred to herein as "instructive" properties. While this alleviates the costs and off-target risks associated with exogenous growth factors, the scaffold must be potently instructive to achieve tissue growth. Moreover, toward achieving functionality, such a scaffold should also recapitulate the spatial complexity of the osteochondral tissues. Thus, in addition to the regeneration of the articular cartilage and underlying cancellous bone, the complex osteochondral interface, composed of calcified cartilage and subchondral bone, should also be restored. In this Perspective, we highlight recent synthetic-based, instructive osteochondral scaffolds that have leveraged new material chemistries as well as innovative fabrication strategies. In particular, scaffolds with spatially complex chemical and morphological features have been prepared with electrospinning, solvent-casting-particulate-leaching, freeze-drying, and additive manufacturing. While few synthetic scaffolds have advanced to clinical studies to treat OCDs, these recent efforts point to the promising use of the chemical and physical properties of synthetic materials for regeneration of osteochondral tissues.

In situ hydrogel dressing loaded with heparin and basic fibroblast growth factor for accelerating wound healing in rat.

In order to accelerate the healing of chronic wound, a hydrogel dressing encapsulating with heparin and basic fibroblast growth factor is prepared by the Michael addition of 4-arm acrylated polyethylene glycol and dithiothreitol. As-prepared hydrogel dressing can combine the advantages of wet healing theory and exogenous growth factor supplement. Furthermore, the encapsulated heparin can play a role in diminishing inflammation and accelerating wound healing in addition to its well-known function of stabilizing basic fibroblast growth factor. In vitro release test shows the hydrogel network is able to sustainably release basic fibroblast growth factor within 10days by the regulation of heparin, while released growth factor can significantly promote fibroblast's proliferation in vitro. Moreover, the wound healing in rat shows that as-prepared hydrogel dressing could accelerate wound healing in vivo much more effectively compared with blank hydrogel dressing and negative control. Hematoxylin-eosin and Masson's Trichrome staining exhibit the formation of complete and uniform epidermis. Immunohistochemical staining exhibits heparin can help hydrogel dressing to possess low inflammation in early stage, which is beneficial for accelerating wound healing as well as preventing the production of scar tissue. The enzyme-linked immunosorbent assay results demonstrate the exogenous bFGF in hydrogel can significantly upgrade the expressing of vascular endothelial growth factor and transforming growth factor-β in wound site, which indicate better angiogenesis, and better on-site cell proliferation in wound site, respectively. Those results are further demonstrated by immunohistochemical and immunofluorescence staining. Consequently, as-prepared hydrogel dressing shows promising potential to perform better therapy efficacy in clinic for accelerating wound healing.

Mechanical-chemical coupled modeling of bone regeneration within a biodegradable polymer scaffold loaded with VEGF.

Repairing critical-size bone defects with engineered scaffolds remains a challenge in orthopedic practice. Insufficient vascularization is a major reason causing the failure of bone regeneration within scaffolds. Loading exogenous vascular endothelial growth factor (VEGF) in biodegradable polymer scaffolds and controlling its release rate can promote vascularization in scaffolds and accelerate bone regeneration during bone repair. In this study, we developed a 3D mechanical-chemical model of bone regeneration, which combines multiple mechanical-chemical factors including mechanical stimulation, scaffold degradation, VEGF release and transportation, vascularization and oxygen delivery. This model simulated the coupled dynamic mechanical-chemical environments during bone regeneration and scaffold degradation and predicted bone growth under different mechanical-chemical conditions. Moreover, the predictive power of the model was preliminarily validated by experimental data in literature. Based on the validated model, the effect of exogenous VEGF doses on bone regeneration and the optimal doses under different mechanical stimulations was investigated. The simulation results suggested that there was an optimal range of VEGF doses, which promoted the efficiency of bone regeneration, and an appropriate mechanical stimulation improved the effect of VEGF on bone regeneration. The present work may provide a useful platform for future design of bone scaffolds to regenerate functional bones.

Exogenous fibroblast growth factor 1 ameliorates diabetes-induced cognitive decline via coordinately regulating PI3K/AKT signaling and PERK signaling

BackgroundDiabetes induces central nervous system damage, leading to cognitive decline. Fibroblast growth factor 1 (FGF1) has dual function of neuroprotection and normalizing hyperglycemia. To date, the precise mechanisms and potential treating strategies of FGF1 for diabetes-induced cognitive decline (DICD) hasn’t been fully elucidated.MethodsIn this study, db/db mice were used as DICD animal model. We found that diabetes remarkably suppressed FGF1 expression in hippocampus. Thus, exogenous FGF1 had been treated for db/db mice and SH-SY5Y cells.ResultsFGF1 significantly ameliorates DICD with better spatial learning and memory function. Moreover, FGF1 blocked diabetes-induced morphological structure change, neuronal apoptosis and Aβ1–42 deposition and synaptic dysfunction in hippocampus. But normalizing glucose may not the only contributed factor for FGF1 treating DICD with evidencing that metformin-treated db/db mice has a inferior cognitive function than that in FGF1 group. Current mechanistic study had found that diabetes inhibits cAMP-response element binding protein (CREB) activity and subsequently suppresses brain derived neurotrophic factor (BDNF) level via coordinately regulating PERK signaling and PI3K/AKT signaling in hippocampus, which were reversed by FGF1.ConclusionWe conclude that FGF1 exerts its neuroprotective role and normalizing hyperglycemia effect, consequently ameliorates DICD, implying FGF1 holds a great promise to develop a new treatment for DICD.61Q3XReLNTPu_dAr92-AxWVideo abstract

Chondrogenic potential of animal adult stem cells through electrical stimulation

Background & Aim Mesenchymal stem cells (MSCs) represent an appealing alternative cell source for cartilage repair. There are studies that induce differentiation into cartilage cells by treating the growth factors in MSCs or altering the properties of MSCs by genetic modification. Electrical stimulation (ES) is known to guide the development and regeneration of many tissues. Use of low-frequency ES for therapeutic purposes has been increasing during the last decades. In this study, we exposed equine adipose tissue-derived MSCs (eAD-MSCs) to ES and assessed changes in the chondrogenic differentiation potential. Methods, Results & Conclusion The cells obtained from equine adipose tissue attached to culture plates and expanded in vitro. Flow cytometric analysis at third passage indicated that the cells were strongly positive for CD44, CD90, and CD105, but negative for CD13, CD34, and CD45. ES was applied to eAD-MSCs cultured under condition of high-density micro-mass under ES of 10 V/cm, with duration of 10 ms and a frequency of 2.0 Hz for three days. We compared chondrogenic differentiation potential of non-ES and ES condition. Expression levels of chondrogenic potential-related markers were examined by quantitative real-time RT-PCR. Articular cartilage is divided into a hyaline cartilage layer and a fibrous cartilage layer. Osteoarthritis (OA) is a disease caused by the natural degeneration of cartilage layer. From the beginning, OA of the middle stage leads to damage of the hyaline cartilage, and damage of the fibrous cartilage at the last stage. We observed the differentiation potential of eAD-MSCs into chondrocytes by specific ES in absence of exogenous growth factors. Gene expression of chondrogenic markers such as type II collagen (COL2A1), Aggrecan, and Sox9 was analyzed at 3 days of ES. Based on the mechanism that chondrocyte formation in articular cavity starts from the aggregation of cells, we observed the differentiation potential of eAD-MSCs into chondrocytes by specific ES in absence of exogenous growth factors. Therefore, this study might contribute to the differentiation of stem cells into cartilage cells by inducing pre-chondrogenic condensation under specific ES.

Effect of electrical stimulation on chondrogenic differentiation of mesenchymal stem cells cultured in hyaluronic acid – Gelatin injectable hydrogels

Electrical stimulation (ES) has provided enhanced chondrogenesis of mesenchymal stem cells (MSCs) cultured in micro-mass without the addition of exogenous growth factors. In this study, we demonstrate for the first time that ES of MSCs encapsulated in an injectable hyaluronic acid (HA) – gelatin (GEL) mixture enhances the chondrogenic potential of the hydrogel. Samples were stimulated for 21 days with 10 mV/cm at 60 kHz, applied for 30 min every 6 h a day. Mechanical properties of hydrogels were higher if the precursors were dissolved in Calcium-Free Krebs Ringer Buffer (G′ = 1141 ± 23 Pa) compared to those diluted in culture media (G′ = 213 ± 19 Pa). Cells within stimulated hydrogels were rounder (55%) than non-stimulated cultures (32%) (p = 0.005). Chondrogenic markers such as SOX-9 and aggrecan were higher in stimulated hydrogels compared to controls. The ES demonstrated that normalized content of glycosaminoglycans and collagen to DNA was slightly higher in stimulated samples. Additionally, collagen type II normalized to total collagen was 2.43 times higher in stimulated hydrogels. These findings make ES a promising tool for enhancing articular cartilage tissue engineering outcomes by combining hydrogels and MSCs.

Injectable Therapeutic Organoids Using Sacrificial Hydrogels

SummaryOrganoids are becoming widespread in drug-screening technologies but have been used sparingly for cell therapy as current approaches for producing self-organized cell clusters lack scalability or reproducibility in size and cellular organization. We introduce a method of using hydrogels as sacrificial scaffolds, which allow cells to form self-organized clusters followed by gentle release, resulting in highly reproducible multicellular structures on a large scale. We demonstrated this strategy for endothelial cells and mesenchymal stem cells to self-organize into blood-vessel units, which were injected into mice, and rapidly formed perfusing vasculature. Moreover, in a mouse model of peripheral artery disease, intramuscular injections of blood-vessel units resulted in rapid restoration of vascular perfusion within seven days. As cell therapy transforms into a new class of therapeutic modality, this simple method—by making use of the dynamic nature of hydrogels—could offer high yields of self-organized multicellular aggregates with reproducible sizes and cellular architectures.

Computer-Controlled Biaxial Bioreactor for Investigating Cell-Mediated Homeostasis in Tissue Equivalents.

Soft biological tissues consist of cells and extracellular matrix (ECM), a network of diverse proteins, glycoproteins, and glycosaminoglycans that surround the cells. The cells actively sense the surrounding ECM and regulate its mechanical state. Cell-seeded collagen or fibrin gels, so-called tissue equivalents, are simple but powerful model systems to study this phenomenon. Nevertheless, few quantitative studies document the stresses that cells establish and maintain in such gels; moreover, most prior data were collected via uniaxial experiments whereas soft tissues are mainly subject to multiaxial loading in vivo. To begin to close this gap between existing experimental data and in vivo conditions, we describe here a computer-controlled bioreactor that enables accurate measurements of the evolution of mechanical tension and deformation of tissue equivalents under well-controlled biaxial loads. This device allows diverse studies, including how cells establish a homeostatic state of biaxial stress and if they maintain it in response to mechanical perturbations. It similarly allows, for example, studies of the impact of cell and matrix density, exogenous growth factors and cytokines, and different types of loading conditions (uniaxial, strip-biaxial, and biaxial) on these processes. As illustrative results, we show that NIH/3T3 fibroblasts establish a homeostatic mechanical state that depends on cell density and collagen concentration. Following perturbations from this homeostatic state, the cells were able to recover biaxial loading similar to homeostatic. Depending on the precise loads, however, they were not always able to fully maintain that state.

Mouse vestibular supporting cells induce directional differentiation of human amniotic fluid stem cells into functional neurons: a pilot study

Objective: To investigate the feasibility of inducing human amniotic fluid stem cells into functional neurons by supporting contact co-culture depended on feeder layer from mouse vestibular supporting cells. Methods: Human amniotic fluid stem cells were isolated to culture. The vestibular tissues were obtained from the newborn C57BL/6J mouse by enzymatic digestion and cell culture, the hollow spheres were selected to prepare a monolayer feeder layer. The nGFP-labeled amniotic fluid stem cells were planted on the surface of the feeder layer to form the supporting contact co-culture without adding any exogenous nerve growth factor and neuronal signal inducing factor, and detected the expression of Tuj1 and PSD95, and investigated whether there were ion channels in neurons by FM1-43. Human amniotic fluid stem cells and mouse vestibular supporting cells, which were differentiated separately, and Transwell coculture was used as the control group. Results: The feeder layer expressed the special marker P27(kip1)of the inner ear supporting cell. The nGFP-labeled amniotic fluid stem cells were inoculated on the feeder layer, and (52.0±3.0)% of the nGFP cells expressed Tuj1,which had typical neurons morphological characteristics[protrusion length (110.7±6.2) μm]; the feeder layer cells were differentiated separately, of which (1.1±0.6) % expressed Tuj1 in the control group; the amniotic fluid stem cells were differentiated independently without typical neuron morphological features [protrusion length (16±4.1) μm], of which (92.0±1.0) % expressed Tuj1. The amniotic fluid stem cells and the feeder layer were co-cultured in Transwell: although (92.0±1.0)% of amniotic fluid stem cells had the expression of Tuj1, which had no typical neurons morphological feature[protrusion length (17±4.5) μm], only (1.2±0.9) % of Tuj1 were observed in the feeder layer. Conclusion: By supporting contact co-culture, the feeder layer from the vestibular supporting cells can successfully differentiate human amniotic fluid stem cells into neurons.

HUMAN ALLOGRAFTS IMPROVE HEALING OUTCOMES IN CHRONIC WOUNDS

BackgroundChronic wounds affect an estimated 8 million people worldwide and are often a result of underlying health conditions, such as obesity, diabetes, malnutrition, etc. The related morbidity and mortality places an increased burden on the healthcare system. Regenerative approaches, which engages and stimulates the body’s innate healing capabilities is addressing the limited successes in current standard of care treatments. Axolotl Biologix is a regenerative medicine company that produces allograft products from the human amnion. Axolotl Ambient™ and Shot™, conditioned media rich in cytokines and growth factors, are derived from human amniotic mesenchymal stromal cells. Axolotl DualGraft™ is a dehydrated, acellular, double layer, human amniotic membrane that encourages soft tissue repair by serving as a barrier, extracellular matrix scaffold, and provides a source of matrix‐bound growth factors.MethodsBoth allografts were used to facilitate repair and regeneration in a patient with difficult to close or intractable full‐thickness wounds. Axolotl Ambient™ was injected into the wound margin and Axolotl DualGraft™ was placed within the exposed wound bed. Wounds were bandaged per standard of care and imaged regularly to monitor wound healing progression. A range of bioassays were performed to ascertain the biological activity of the allografts.ResultsMultiple applications and injections of Ambient and DualGraft resulted in the formation of granulation tissue, restoration of blood flow, pain sensation, epithelialization, and wound closure. Bioassays confirmed the allografts contain measurable amounts of growth factors that promote angiogenesis, proliferation, tissue remodeling and reduction in inflammation.ConclusionsClinical application of the allografts in intractable wounds yielded dramatic improvement in wound repair by stimulating the normal physiological wound healing processes by the addition of exogenous growth factors, providing a scaffold in the wound bed, promoting normal blood flow, re‐epithelialization, and tissue remodeling. Longitudinal case studies are ongoing, concurrent with benchtop research to further elucidate the mechanisms of action responsible for reported clinical benefits in difficult to heal wounds.Support or Funding InformationN/A

Effects and mechanism of rat epidermal stem cells treated with exogenous vascular endothelial growth factor on healing of deep partial-thickness burn wounds in rats

Effects and mechanism of rat epidermal stem cells treated with exogenous vascular endothelial growth factor on healing of deep partial-thickness burn wounds in rats

A Static Self-Directed Method for Generating Brain Organoids from Human Embryonic Stem Cells.

Human brain organoids differentiated from embryonic stem cells offer the unique opportunity to study complicated interactions of multiple cell types in a three-dimensional system. Here we present a relatively straightforward and inexpensive method that yields brain organoids. In this protocol human pluripotent stem cells are broken into small clusters instead of single cells and grown in basic media without a heterologous basement membrane matrix or exogenous growth factors, allowing the intrinsic developmental cues to shape the organoid's growth. This simple system produces a diversity of brain cell types including glial and microglial cells, stem cells, and neurons of the forebrain, midbrain, and hindbrain. Organoids generated from this protocol also display hallmarks of appropriate temporal and spatial organization demonstrated by brightfield images, histology, immunofluorescence and real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). Because these organoids contain cell types from various parts of the brain, they can be utilized for studying a multitude of diseases. For example, in a recent paper we demonstrated the use of organoids generated from this protocol for studying the effects of hypoxia on the human brain. This approach can be used to investigate an array of otherwise difficult to study conditions such as neurodevelopmental handicaps, genetic disorders, and neurologic diseases.

Tree shrew bone marrow-derived mesenchymal stem cells express CD81, OCLN, and miR-122, facilitating the entire hepatitis C virus life cycle.

Hepatitis C virus (HCV) infection is a major cause of chronic liver disease and associated cirrhosis, and hepatocellular carcinoma worldwide. At present, there is no prophylactic vaccine against HCV due to the lack of in vivo and in vitro model systems. Although most recombinants of all major HCV genotypes replicate in Huh-7 cell line and derivatives, these cells are human hepatoma-derived cell line. Therefore, the development of un-tumor-derived cell systems facilitating the entire HCV life cycle is urgently needed. In this study, we aimed to establish a novel tree shrew-derived bone marrow-derived mesenchymal stem cell (BM-MSC) system to reconstruct the HCV life cycle. We transduction cluster of differentiation 81 (CD81), occludin (OCLN), and microRNA-122 (miR-122) into BM-MSCs, then used a well-established HCV, produced from the J6/JFH1-Huh7.5.1 culture system, to infect the cells. We observed that BM-MSCs transduction with CD81/OCLN or CD81/OCLN/miR-122 support HCV RNA replication and infectious virus production. We also found that the addition of exogenous vascular endothelial growth factor (VEGF) can enhance HCV infectivity in BM-MSCs, with HCV virus load up to 105 copies/mL. In conclusion, we identified the minimum essential factors required for HCV replication in tree shrew-derived nonhuman nonhepatic BM-MSCs. Further, we identified that exogenous addition of VEGF, and exogenous expression of CD81, OCLN, and miR-122, facilitates efficient viral replication and production of infectious particles. Our results describe a novel cell system capable of supporting the entire HCV life cycle, which may provide an essential tool for anti-HCV drug discovery, vaccine development, and study of pathogenesis.

Growth‐Factor Free Multicomponent Nanocomposite Hydrogels That Stimulate Bone Formation

AbstractSynthetic osteo‐promoting materials that are able to stimulate and accelerate bone formation without the addition of exogenous cells or growth factors represent a major opportunity for an aging world population. A co‐assembling system that integrates hyaluronic acid tyramine (HA‐Tyr), bioactive peptide amphiphiles (GHK‐Cu2+), and Laponite (Lap) to engineer hydrogels with physical, mechanical, and biomolecular signals that can be tuned to enhance bone regeneration is reported. The central design element of the multicomponent hydrogels is the integration of self‐assembly and enzyme‐mediated oxidative coupling to optimize structure and mechanical properties in combination with the incorporation of an osteo‐ and angio‐promoting segments to facilitate signaling. Spectroscopic techniques are used to confirm the interplay of orthogonal covalent and supramolecular interactions in multicomponent hydrogel formation. Furthermore, physico‐mechanical characterizations reveal that the multicomponent hydrogels exhibit improved compressive strength, stress relaxation profile, low swelling ratio, and retarded enzymatic degradation compared to the single component hydrogels. Applicability is validated in vitro using human mesenchymal stem cells and human umbilical vein endothelial cells, and in vivo using a rabbit maxillary sinus floor reconstruction model. Animals treated with the HA‐Tyr‐HA‐Tyr‐GHK‐Cu2+ hydrogels exhibit significantly enhanced bone formation relative to controls including the commercially available Bio‐Oss.

Effect of Pulsed Electromagnetic Fields on Human Mesenchymal Stem Cells Using 3D Magnetic Scaffolds.

Alternative bone regeneration strategies that do not rely on harvested tissue or exogenous growth factors are needed. One of the major challenges in tissue reconstruction is recreating the bone tissue microenvironment using the appropriate combination of cells, scaffold, and stimulation to direct differentiation. This study presents a bone regeneration formulation that involves the use of human adipose‐derived mesenchymal stem cells (hASCs) and a three‐dimensional (3D) hydrogel scaffold based on self‐assembled RADA16 peptides containing superparamagnetic iron oxide nanoparticles (NPs). Although superparamagnetic NPs could be used as stimulus to manipulate the cell proliferation and differentiation, in this paper their use is explored for assisting osteogenic differentiation of hASCs in conjunction with direct stimulation by extremely low‐frequency pulsed electromagnetic fields (pEMFs). Cellular morphology, proliferation, and viability, as well as alkaline phosphatase activity, calcium deposition, and osteogenic capacity were monitored for cells cultured up to 21 days in the 3D construct. The results show that the pEMFs and NPs do not have any negative effect on cell viability, but instead distinctly induced early differentiation of hASCs to an osteoblastic phenotype, when compared with cells without biophysical stimulation. This effect is attributed to synergy between the pEMFs and NPs, which may have stimulated mechanotransduction pathways, which, in turn activated biochemical signals between cells to differentiate or proliferate. This approach may offer a safe and effective option for the treatment of non‐union bone fractures. Bioelectromagnetics. © 2020 The Authors. Bioelectromagnetics published by Wiley Periodicals, Inc.

Biofunctionalized chondrogenic shape-memory ternary scaffolds for efficient cell-free cartilage regeneration

Cartilage defect repair remains a great clinical challenge due to the limited self-regeneration capacity of cartilage tissue. Surgical treatment of injured cartilage is rather difficult due to the narrow space in the articular cavity and irregular defect area. Herein, we designed and fabricated chondrogenic and physiological-temperature-triggered shape-memory ternary scaffolds for cell-free cartilage repair, where the poly (glycerol sebacate) (PGS) networks ensured elasticity and shape recovery, crystallized poly (1,3-propylene sebacate) (PPS) acted as switchable phase, and immobilized bioactive kartogenin (KGN) endowed the scaffolds with chondrogenic capacity. The resultant scaffolds exhibited shape-memory properties with shape-memory fixed ratio of 98% and recovered ratio of 97% at 37°C for PPS/PGS/KGN-100, indicating a good potential for minimally invasive implantation. The scaffolds gradually degraded in Dulbecco's phosphate-buffered saline and released KGN up to 12 weeks in vitro. In addition, the scaffolds promoted chondrogenic differentiation while inhibiting osteogenic differentiation of bone marrow-derived mesenchymal stem cells in a concentration-dependent manner and cartilage regeneration in full-thickness defects of rat femoropatellar groove for 12 weeks. Consequently, the PPS/PGS/KGN-100 scaffolds stimulated the formation of an overlying layer of neocartilage mimicking the characteristic architecture of native articular cartilage even in the absence of exogenous growth factors and seeded cells. This study provides much inspiration for future research on cartilage tissue engineering. Statement of SignificanceThere are two crucial challenges for cartilage defect repair: the lack of self-regeneration capacity of cartilage tissue and difficult scaffold implantation via traditional open surgery due to space-limited joints. Herein, bioactive body-temperature-responsive shape memory scaffolds are designed to simultaneously address the challenges. The scaffolds can be readily implanted by minimally invasive approach and recover by body-temperature of patient. The integration of kartogenin endows scaffolds the bioactivity, leading to the first example of bulk shape-memory scaffolds for cell-free cartilage repair. These characteristics make the scaffolds advantageous for clinical translation. Moreover, our developed material is easy to be functionalized due to the presence of extensive free hydroxyl groups and provides a versatile platform to design diverse functional shape memory biomaterials.

Resveratrol promotes secretion of wound healing related growth factors of mesenchymal stem cells originated from adult and fetal tissues

Non-healing wounds have demonstrated aberrant regulation of several growth factors, thus using exogenous growth factors and cytokines in the clinical setting may improve the outcomes of non-healing wounds. Mesenchymal stem cells (MSCs) are the source of growth factors that show beneficial effect in promoting impaired wound healing. Certain culture condition should be developed to stimulate growth factor secretion from stem cell. Resveratrol, a small molecule found to increase MSCs therapeutic effectiveness. This study aims to investigate the effect of RV on secretion of wound healing related growth factors. We isolated and characterised MSCs from wharton’s jelly (WJ), amniotic membrane (AM), and adipose tissue. We treated MSCs with serum deprived medium (SDM) supplemented with RV at 0.1 µM, 0.5 µM, 0.8 µM concentration. Our study revealed that RV at 0.1 µM was more effective to increase cell proliferation rate. Resveratrol at 0.1 µM promoted EGF, HGF, PDGF, and TGF-β1 secretion from MSCs. AD-MSCs showed the greatest response to RV stimulation in the term of cell proliferation and growth factors secretion. As conclusion, RV can facilitate cell proliferation and wound healing related growth factors secretion at dosage dependent manner.

Transfection of Exogenous Fibroblast Growth Factor (FGF) on Human Embryonic Stem Cells (ESCs) as a Regenerative Agent for Patients with Type 1 Diabetes Mellitus (T1DM)

Type 1 Diabetes Mellitus (T1DM) is an autoimmune disorder which results in the INS pancreatic β-cell destruction and contributes to around 5 to 10% of all diabetes mellitus cases, especially in children. At the moment, the only treatment for T1DM is by insulin injection, which is injected in order to prevent the complication of T1DM. However, several studies have shown that combination between Embryonic Stem Cells (ESCs) and the Fibroblast Growth Factor 2 (FGF-2) may be a successful modality to treat T1DM. Actually, the ESCs may become the potential therapy in treating T1DM.