Poly Lactic-co-glycolic Acid Scaffolds Research Articles

Plasma-Treated Electrospun PLGA Nanofiber Scaffold Supports Limbal Stem Cells

The corneal epithelial layer is continuously replaced by limbal stem cells. Reconstructing this layer in vitro using synthetic scaffolds is highly needed. Poly-lactic-co-glycolic acid (PLGA) is approved for human use due to its biocompatibility and biodegradability. However, PLGA is hydrophobic, preventing cell adherence to PLGA membranes. PLGA scaffolds were prepared by electrospinning on a custom-made target drum spinning at a rate of 1000 rpm with a flow rate of 0.5 mL/h and voltage at 20 kV, then treated with oxygen plasma at 30 mA using a vacuum coater. Scaffolds were characterized by SEM, mechanically by tensile testing, and thermally by DSC and TGA. In vitro degradation was measured by weight loss and pH drop. Wettability was assessed through water uptake and contact angles measurements. Human limbal stem cells (hLSCs) were isolated and seeded on the scaffolds. Cell attachment and cytotoxicity assay were evaluated on day 1 and 5 after cell seeding. SEM showed regular fiber morphology with diameters ranging between 150 nm and 950 nm. Tensile strength demonstrated similar average stress values for both plasma- and non-plasma-treated samples. Scaffolds also showed gradual degradability over a period of 7–8 weeks. Water contact angle and water absorption were significantly enhanced for plasma-treated scaffolds, indicating a favorable increase in their hydrophilicity. Scaffolds have also supported hLSCs growth and attachment with no signs of cytotoxicity. We have characterized a nanofiber electrospun plasma-treated PLGA scaffold to investigate the mechanical and biological properties and the ability to support the attachment and maintenance of hLSCs.

Large-scale expansion of human umbilical cord-derived mesenchymal stem cells using PLGA@PLL scaffold

Mesenchymal stem cells (MSCs) are highly important in biomedicine and hold great potential in clinical treatment for various diseases. In recent years, the capabilities of MSCs have been under extensive investigation for practical application. Regarding therapy, the efficacy usually depends on the amount of MSCs. Nevertheless, the yield of MSCs is still limited due to the traditional cultural methods. Herein, we proposed a three-dimensional (3D) scaffold prepared using poly lactic-co-glycolic acid (PLGA) nanofiber with polylysine (PLL) grafting, to promote the growth and proliferation of MSCs derived from the human umbilical cord (hUC-MSCs). We found that the inoculated hUC-MSCs adhered efficiently to the PLGA scaffold with good affinity, fast growth rate, and good multipotency. The harvested cells were ideally distributed on the scaffold and we were able to gain a larger yield than the traditional culturing methods under the same condition. Thus, our cell seeding with a 3D scaffold could serve as a promising strategy for cell proliferation in the large-scale production of MSCs. Moreover, the simplicity and low preparation cost allow this 3D scaffold to extend its potential application beyond cell culture.Graphical

In Vitro Enhanced Osteogenic Potential of Human Mesenchymal Stem Cells Seeded in a Poly (Lactic-co-Glycolic) Acid Scaffold: A Systematic Review.

Human bone marrow stem cells (hBMSCs) and human adipose-derived stem cells (hADSCs) have demonstrated the capability to regenerate bone once they have differentiated into osteoblasts. This systematic review aimed to evaluate the in vitro osteogenic differentiation potential of these cells when seeded in a poly (lactic-co-glycolic) acid (PLGA) scaffold. A literature search of 4 databases following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted in January 2021 for studies evaluating the osteogenic differentiation potential of hBMSCs and hADSCs seeded in a PLGA scaffold. Only in vitro models were included. Studies in languages other than English were excluded. A total of 257 studies were identified after the removal of duplicates. Seven articles fulfilled our inclusion and exclusion criteria. Four of these reviews used hADSCs and three used hBMSCs in the scaffold. Upregulation in osteogenic gene expression was seen in all the cells seeded in a 3-dimensional scaffold compared with 2-dimensional films. High angiogenic gene expression was found in hADSCs. Addition of inorganic material to the scaffold material affected cell performance. Viability, proliferation, and differentiation of cells strongly depend on the environment where they grow. There are several factors that can enhance the differentiation capacity of stem cells. A PLGA scaffold proved to be a biocompatible material capable of boosting the osteogenic differentiation potential and mineralization capacity in hBMSCs and hADSCs.

Characteristic Evaluation of Recombinant MiSp/Poly(lactic-co-glycolic) Acid (PLGA) Nanofiber Scaffolds as Potential Scaffolds for Bone Tissue Engineering.

Biomaterial-based nanofibrous scaffolds are the most effective alternative to bone transplantation therapy. Here, two recombinant minor ampullate spidroins (spider silk proteins), R1SR2 and NR1SR2C, were blended with Poly(lactic-co-glycolic) Acid (PLGA), respectively, to generate nanofiber scaffolds by electrospinning. The N-terminal (N), C-terminal (C), repeating (R1 and R2) and spacer (S) modules were all derived from the minor ampullate spidroins (MiSp). The physical properties and structures of the blended scaffolds were measured by scanning electron microscopy (SEM), water contact angle measurement, Fourier transform infrared spectroscopy (FTIR), Differential scanning calorimetry (DSC), and Tensile mechanical testing. The results showed that blending of MiSp (R1SR2 and NR1SR2C) reduced the diameter of nanofibers, increased the porosity and glass transition temperatures of nanofibrous scaffolds, and effectively improved the hydrophilicity and ultimate strain of scaffolds. It is worth noting that the above changes were more significant in the presence of the N- and C-termini of MiSp. In cell culture assays, human bone mesenchymal stem cells (HBMSCs) grown on NR1SR2C/PLGA (20/80) scaffolds displayed markedly enhanced proliferative and adhesive abilities compared with counterparts grown on pure PLGA scaffolds. Jointly, these findings indicated recombinant MiSp/PLGA, particularly NR1SR2C/PLGA (20/80) blend nanofibrous scaffolds, is promising for bone tissue engineering.

Investigation of Cell Adhesion and Cell Viability of the Endothelial and Fibroblast Cells on Electrospun PCL, PLGA and Coaxial Scaffolds for Production of Tissue Engineered Blood Vessel.

Endothelialization of artificial scaffolds is considered an effective strategy for increasing the efficiency of vascular transplantation. This study aimed to compare the biophysical/biocompatible properties of three different biodegradable fibrous scaffolds: Poly (ɛ-caprolactone) (PCL) alone, Poly Lactic-co-Glycolic Acid (PLGA) alone (both processed using Spraybase® electrospinning machine), and Coaxial scaffold where the fiber core and sheath was made of PCL and PLGA, respectively. Scaffold structural morphology was assessed by scanning electron microscope and tensile testing was used to investigate the scaffold tension resistance over time. Biocompatibility studies were carried out with human umbilical vein endothelial cells (HUVEC) and human vascular fibroblasts (HVF) for which cell viability (and cell proliferation over a 4-day period) and cell adhesion to the scaffolds were assessed by cytotoxicity assays and confocal microscopy, respectively. Our results showed that all biodegradable polymeric scaffolds are a reliable host to adhere and promote proliferation in HUVEC and HVF cells. In particular, PLGA membranes performed much better adhesion and enhanced cell proliferation compared to control in the absence of polymers. In addition, we demonstrate here that these biodegradable membranes present improved mechanical properties to construct potential tissue-engineered vascular graft.

Synthesis of Ce/Gd@HA/PLGA Scaffolds Contributing to Bone Repair and MRI Enhancement.

It is important for future clinical applications to design and synthesize multipurpose scaffolding materials for bone tissue engineering with high osteogenic induction and MRI capability. In the present study, we synthesized Ce/Gd@HA by co-doping Ce3+ and Gd3+ into hydroxyapatite (HA) using a hydrothermal synthesis method, and then Ce/Gd@HA composites were synthesized by combining Ce/Gd@HA nanoparticles with polylactic-co-glycolic acid (PLGA) to investigate whether implanted Ce/Gd@HA/PLGA composites could promote osteoblast viability, leading to tibia repair of the rats and enhance MRI. The measurement results contain X-ray diffraction (XRD), Fourier-transform infrared (FTIR) spectroscopy, and environmental scanning electron microscopy (ESEM) showing that HA doped with Ce3+ and Gd3+ was still a hexagonal crystal with high crystallinity. The synthesized Ce/Gd@HA/PLGA composites have a structure and obvious magnetic resonance imaging (MRI) capability. The in vitro experimental results indicated that Ce/Gd@HA/PLGA composites significantly promoted the performance of MC3T3-E1 cells, containing proliferation, adhesion, and osteogenic differentiation capacities. These include the improvement of alkaline phosphatase activity, enhancement of mineral deposition, and upregulation of OCN and COL-1 gene expression. The in vivo experimental results demonstrated that the Ce/Gd@HA/PLGA composites significantly improved the healing rate of rat bone defects. The MRI images indicated that the Ga-doped composites were observed in the MRI T1 sequence in rats. The aforementioned results suggested that Ce/Gd@HA/PLGA composites not only effectively promoted bone formation but also enhanced MRI capability. The composites synthesized in this study have great potential in bone regeneration with an extensive application in bone tissue engineering.

Improved porosity of electrospun poly (Lactic-Co-Glycolic) scaffolds by sacrificial microparticles enhances cellular infiltration compared to sacrificial microfiber.

Electrospinning is a technique used to fabricate nano-/microfiber scaffolds for tissue engineering applications. However, a major limitation of electrospun scaffolds is the high packing density of fibers that leads to poor cellular infiltration. Thus, incorporation of a water soluble sacrificial porogen, polyethylene oxide (PEO), was utilized to fine-tune the porous fraction of the scaffolds and decrease fiber packing density. Poly(lactic-co-glycolic) acid (PLGA) scaffolds were either co-electrospun with sacrificial PEO microfibers or co-electrosprayed with sacrificial PEO microparticles at three different extrusion rates to control the relative morphology and dose of PEO. A dose-dependent response in PLGA scaffold bulk porosity and pore area was noted as PEO content was increased. Notably, PLGA scaffolds after removal of sacrificial PEO microparticles significantly increased the porous fraction and pore area approximately 8, 10, and 14% and 46, 20, and 33μm2, respectively, relative to the analogous PEO microfiber scaffold. The tensile properties of the more porous PLGA scaffolds after PEO microparticle removal, remained stable for all extrusion rates of PEO tested, relative to the PLGA scaffolds after PEO microfiber removal. Histological analysis revealed that removal of PEO microparticles significantly increased the depth of cellular migration through the PLGA scaffolds, relative to PEO microfiber scaffolds, with maximum migratory depths of 1120μm versus 150μm over 28 days, respectively. Additionally, depth of cellular infiltration responded dose-dependently in the PEO microparticle scaffolds, whereas in the PEO microfiber scaffolds there was no correlation. Further analysis with Masson's Trichrome staining and electron microscopy revealed that collagen density and depth of deposition substantially increased in PLGA scaffolds after removal of PEO microparticles relative to PEO microfibers. Thus, this study demonstrates an effective strategy to control the porous fraction of electrospun scaffolds via the incorporation of sacrificial PEO microparticles, without significant decreases in mechanical properties, thereby enhancing cellular infiltration and subsequent extracellular matrix deposition.

Tri-Layered and Gel-Like Nanofibrous Scaffolds with Anisotropic Features for Engineering Heart Valve Leaflets.

3D heterogeneous and anisotropic scaffolds that approximate native heart valve tissues are indispensable for the successful construction of tissue engineered heart valves (TEHVs). In this study, novel tri-layered and gel-like nanofibrous scaffolds, consisting of poly(lactic-co-glycolic) acid (PLGA) and poly(aspartic acid) (PASP), are fabricated by a combination of positive/negative conjugate electrospinning and bioactive hydrogel post-processing. The nanofibrous PLGA-PASP scaffolds present tri-layered structures, resulting in anisotropic mechanical properties that are comparable with native heart valve leaflets. Biological tests show that nanofibrous PLGA-PASP scaffolds with high PASP ratios significantly promote the proliferation and collagen and glycosaminoglycans (GAGs) secretions of human aortic valvular interstitial cells (HAVICs), compared to PLGA scaffolds. Importantly, the nanofibrous PLGA-PASP scaffolds are found to effectively inhibit the osteogenic differentiation of HAVICs. Two types of porcine VICs, from young and adult age groups, are further seeded onto the PLGA-PASP scaffolds. The adult VICs secrete higher amounts of collagens and GAGs and undergo a significantly higher level of osteogenic differentiation than young VICs. RNA sequencing analysis indicates that age has a pivotal effect on the VIC behaviors. This study provides important guidance and a reference for the design and development of 3D tri-layered, gel-like nanofibrous PLGA-PASP scaffolds for TEHV applications.

Influence of the perfusion bioreactor on Stratified and Distributed approaches for multilayered tissue engineering on biodegradable scaffolds.

Despite wide use and approval of poly lactic-coglycolic acid (PLGA) for surgical applications, there have been very few studies on tissue constructions that mimic physiological multilayer structures by combining PLGA scaffolds with tissue engineering. In our study, we developed a bioreactor system to maintain, and to train two types of three-layered vascular-like structures. Then we examined how the perfusion conditions and different tissue engineering approaches affected the formation of the layered structure and degradation of the PLGA scaffolds. In the proposed Distributed Method, the cells were seeded layer by layer on a single scaffold, using spheroids bigger than scaffold fiber gaps and we achieved the higher cell density compared with the Stratified Method where we stacked three PLGA sheets seeded with individual vascular cell types. At the histological level, scaffold degradation was more prominent in the bioreactor compared to the same time interval in vivo. In addition, the faster flow accelerated the decomposition of PLGA fibers. Moreover, bioreactor perfusion culture at lower flow rates could balance cell adhesion and survival, improve the cell density and promote self-organization of multilayer structure with desirable rate of PLGA scaffolds degradation.

Promotion of Bone Regeneration Using Bioinspired PLGA/MH/ECM Scaffold Combined with Bioactive PDRN.

Current approaches of biomaterials for the repair of critical-sized bone defects still require immense effort to overcome numerous obstacles. The biodegradable polymer-based scaffolds have been required to expand further function for bone tissue engineering. Poly(lactic-co-glycolic) acid (PLGA) is one of the most common biopolymers owing to its biodegradability for tissue regenerations. However, there are major clinical challenges that the byproducts of the PLGA cause an acidic environment of implanting site. The critical processes in bone repair are osteogenesis, angiogenesis, and inhibition of excessive osteoclastogenesis. In this study, the porous PLGA (P) scaffold was combined with magnesium hydroxide (MH, M) and bone-extracellular matrix (bECM, E) to improve anti-inflammatory ability and osteoconductivity. Additionally, the bioactive polydeoxyribonucleotide (PDRN, P) was additionally incorporated in the existing PME scaffold. The prepared PMEP scaffold has pro-osteogenic and pro-angiogenic effects and inhibition of osteoclast due to the PDRN, which interacts with the adenosine A2A receptor agonist that up-regulates expression of vascular endothelial growth factor (VEGF) and down-regulates inflammatory cytokines. The PMEP scaffold has superior biological properties for human bone-marrow mesenchymal stem cells (hBMSCs) adhesion, proliferation, and osteogenic differentiation in vitro. Moreover, the gene expressions related to osteogenesis and angiogenesis of hBMSCs increased and the inflammatory factors decreased on the PMEP scaffold. In conclusion, it provides a promising strategy and clinical potential candidate for bone tissue regeneration and repairing bone defects.

Biodegradable scaffolds facilitate epiretinal transplantation of hiPSC-Derived retinal neurons in nonhuman primates

Transplantation of stem cell-derived retinal neurons is a promising regenerative therapy for optic neuropathy. However, significant anatomic differences compromise its efficacy in large animal models. The present study describes the procedure and outcomes of human-induced pluripotent stem cell (hiPSC)-derived retinal sheet transplantation in primate models using biodegradable materials. Stem cell-derived retinal organoids were seeded on polylactic-coglycolic acid (PLGA) scaffolds and directed toward a retinal ganglion cell (RGC) fate. The seeded tissues showed active proliferation, typical neuronal morphology, and electrical excitability. The cellular scaffolds were then epiretinally transplanted onto the inner surface of rhesus monkey retinas. With sufficient graft–host contact provided by the scaffold, the transplanted tissues survived for up to 1 year without tumorigenesis. Histological examinations indicated survival, further maturation, and migration. Moreover, green fluorescent protein-labeled axonal projections toward the host optic nerve were observed. Cryopreserved organoids were also able to survive and migrate after transplantation. Our results suggest the potential efficacy of RGC replacement therapy in the repair of optic neuropathy for the restoration of visual function. Statement of significanceIn the present study, we generated a human retinal sheet by seeding hiPSC-retinal organoid-derived RGCs on a biodegradable PLGA scaffold. We transplanted this retinal sheet onto the inner surface of the rhesus monkey retina. With scaffold support, donor cells survive, migrate and project their axons into the host optic nerve. Furthermore, an effective cryopreservation strategy for retinal organoids was developed, and the thawed organoids were also observed to survive and show cell migration after transplantation.

An Overview of the Application of Poly(lactic-co-glycolic) Acid (PLGA)-Based Scaffold for Drug Delivery in Cartilage Tissue Engineering

Poly(lactic-co-glycolic) acid (PLGA) has attracted a considerable amount of interest for biomedical application due to its biocompatibility, tailored biodegradation rate (depending on the molecular weight and copolymer ratio), approval for clinical use in humans by the U.S. Food and Drug Administration (FDA), the potential to change surface properties to create better interaction with biological materials and being suitable for export to countries and cultures where planting products with animals is unusable. For commercial use and research, PLGA has been widely studied to control small molecule drugs, proteins, and other macromolecules. This study aims to review the studies that used PLGA scaffolding and its composites as a scaffold and drug delivery in cartilage tissue engineering. It is concluded from the results that the PLGA scaffold as a synthetic scaffold, when combined with natural scaffolds or hybrids, strengthens its biological properties and performs its function better.

Wide-Ranging Multitool Study of Structure and Porosity of PLGA Scaffolds for Tissue Engineering.

In this study, the nanoscale transformation of the polylactic-co-glycolic acid (PLGA) internal structure, before and after its supercritical carbon dioxide (sc-CO2) swelling and plasticization, followed by foaming after a CO2 pressure drop, was studied by small-angle X-ray scattering (SAXS) for the first time. A comparative analysis of the internal structure data and porosity measurements for PLGA scaffolds, produced by sc-CO2 processing, on a scale ranging from 0.02 to 1000 μm, was performed by SAXS, helium pycnometry (HP), mercury intrusion porosimetry (MIP) and both “lab-source” and synchrotron X-ray microtomography (micro-CT). This approach opens up possibilities for the wide-scale evaluation, computer modeling, and prediction of the physical and mechanical properties of PLGA scaffolds, as well as their biodegradation behavior in the body. Hence, this study targets optimizing the process parameters of PLGA scaffold fabrication for specific biomedical applications.

Evaluation Avocado Soybean Unsaponifiables Loaded in Poly (lactic-co-glycolic) Acid/Avocado Soybean Unsaponifiables-Fibrin Nanoparticles Scaffold (New Delivery System) is an Effective Factor for Tissue Engineering.

Background:Growth factors and chemical stimulants have key role in cartilage tissue engineering, but these agents have unfavorable effects on cells. Avocado soybean unsaponifiables (ASU) has chondroprotective and anti-inflammatory effects. In this study, fibrin2nanoparticles (FNP)/ASU, as a new delivery system, with stem cells applied for cartilage tissue engineering in poly (lactic-co-glycolic) acid (PLGA) scaffold.Materials and Methods:FNP/ASU prepared by freeze milling and freeze drying. NFP/ASU was characterized by dynamic light scattering (DLS). PLGA-NFP/ASU scaffold was fabricated and assessed by scanning electron microscope (SEM). Human adipose-derived stem cells (hADSCs) were seeded on scaffold and induced for chondrogenesis. After 14 days, cell viability and gene/protein expression evaluated.Results:The results of DLS and SEM indicated that nanoparticles had high quality. The expression of type II collagen and SOX9 and aggrecan (ACAN) genes in differentiated cells in the presence of ASU was significantly increased compared with the control group (P and lt; 0.01), on the other hand, type I collagen expression was significantly decreased and western blot confirmed it.Conclusions:This study indicated FNP/ASU loaded in PLGA scaffold has excellent effect on chondrogenic differentiation of hADSCs and tissue engineering.

Impact of Fibrin on the Chondrogenic Avocado Soybean Unsaponifiables on Poly (Lactic-co-Glycolic) Acid Scaffold

Synthetic and naturally derived-biodegradable polymers have been applied extensively for scaffold fabrication for cartilage tissue engineering. Human adipose-derived stem cells (hADSCs) seeded in poly (lactic-co-glycolic) acid (PLGA) and PLGA/fibrin scaffolds and cultured in chondrogenic media containing Soybean Unsaponifiables (ASU). All constructs were cultured for 14 days. Cell viability was measured by MTT assay. Chondrogenic differentiation markers, including type II collagen (Coll II), Aggrecan (AGG), and SOX9, were detected by real-time PCR. Hypertrophic and Fibrous differentiation was also analyzed using gene expression type X (Coll X) and Ι (Coll Ι) collagen. The MTT results on the 14th day showed that the viability of hADSCs in the PLGA group was higher than the PLGAL/Fibrin group, but it was not significant. Real-time PCR results demonstrated that SOX9, Coll II, and AGG gene expression in the PLGA and PLGA/Fibrin groups are higher than the control group. The real-time PCR results indicated that Coll X in the PLGA/Fibrin group is lower than the PLGA and control groups. Also, Coll I gene expression in the PLGA group was higher in contrast with the control group. Administrating fibrin with a PLGA scaffold can induce chondrogenesis in hADSCs on chondrogenic media containing ASU.

In Vitro and in Vivo Analysis of Adhesive, Anti-Inflammatory, and Proangiogenic Properties of Novel 3D Printed Hyaluronic Acid Glycidyl Methacrylate Hydrogel Scaffolds for Tissue Engineering.

In this study, we prepared hydrogel scaffolds for tissue engineering by computer-assisted extrusion three-dimensional (3D) printing with photocured (λ = 445 nm) hyaluronic acid glycidyl methacrylate (HAGM). The developed product was compared with the polylactic-co-glycolic acid (PLGA) scaffolds generated by means of the original antisolvent 3D printing methodology. The cytotoxicity and cytocompatibility of the scaffolds were analyzed in vitro by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tests, flow cytometry, and scanning electron microscopy. Anti-inflammatory and proangiogenic properties of the scaffolds were evaluated in the dorsal skinfold chamber mouse model by means of intravital fluorescence microscopy, histology, and immunohistochemistry throughout an observation period of 14 days. In vitro, none of the scaffolds revealed cytotoxicity on days 1, 2, and 5 after seeding with umbilical cord-derived multipotent stromal cells, and the primary cell adhesion to the surface of HAGM scaffolds was low. In vivo, implanted HAGM scaffolds showed enhanced vascularization and host tissue ingrowth, and the inflammatory response to them was less pronounced compared with PLGA scaffolds. The results indicate excellent biocompatibility and vascularization capacity of the developed 3D printed HAGM scaffolds and position them as strong candidates for advanced tissue engineering applications.

3D printing of multilayered scaffolds for rotator cuff tendon regeneration

Repairing massive rotator cuff tendon defects remains a challenge due to the high retear rate after surgical intervention. 3D printing has emerged as a promising technique that enables the fabrication of engineered tissues with heterogeneous structures and mechanical properties, as well as controllable microenvironments for tendon regeneration. In this study, we developed a new strategy for rotator cuff tendon repair by combining a 3D printed scaffold of polylactic-co-glycolic acid (PLGA) with cell-laden collagen-fibrin hydrogels. We designed and fabricated two types of scaffolds: one featuring a separate layer-by-layer structure and another with a tri-layered structure as a whole. Uniaxial tensile tests showed that both types of scaffolds had improved mechanical properties compared to single-layered PLGA scaffolds. The printed scaffold with collagen-fibrin hydrogels effectively supported the growth, proliferation, and tenogenic differentiation of human adipose-derived mesenchymal stem cells. Subcutaneous implantation of the multilayered scaffolds demonstrated their excellent in vivo biocompatibility. This study demonstrates the feasibility of 3D printing multilayered scaffolds for application in rotator cuff tendon regeneration.

Poly lactic-co-glycolic acid scaffold loaded with plasmid DNA encoding fibroblast growth factor-2 promotes periodontal ligament regeneration of replanted teeth.

This study investigated the effects of poly lactic-co-glycolic acid (PLGA) loaded with plasmid DNA encoding fibroblast growth factor-2 (pFGF-2) on human periodontal ligament cells (hPDLCs) in vitro and evaluated the ability of the PLGA/pFGF-2 scaffold to promote periodontal ligament (PDL) regeneration in a beagle dog teeth avulsion animal model. Growth factor and scaffold play important roles in PDL regeneration. PLGA is a kind of biodegradable and biocompatible polymer that can be used as a carrier to deliver growth factors or genes. FGF-2 can induce potent proliferative responses, promote cell migration and regulate the production of extracellular matrix. Therefore, a gene-activated matrix composed of scaffold and genes is supposed to be a superior approach for promoting tissue regeneration. In this study, PLGA and PLGA/pFGF-2 scaffolds were fabricated using electrospinning. The characterization of scaffolds was shown by scanning electron microscope (SEM) and transmission electron microscope (TEM). dsDNA HS was used to test the plasmid release of PLGA/pFGF-2 scaffold. The viability and proliferation of hPDLCs on the two kinds of scaffolds were evaluated by the CCK-8 assay, and the expression of collagen I and scleraxis were analysed by RT-qPCR. The roots of avulsed teeth were covered by the two types of scaffolds and replanted into the alveolar pockets in beagles. Haematoxylin-eosin and Masson staining were used to evaluate the effects of PLGA/pFGF-2 scaffold on promoting PDL regeneration. The smooth and uniform fibres can be observed in both scaffolds, and the plasmids were randomly distributed in the PLGA/pFGF-2 scaffold. dsDNA HS analysis demonstrated that the PLGA/pFGF-2 scaffold released up to 123ng pFGF-2 over 21days in a sustained manner without any obvious burst release. The PLGA/pFGF-2 scaffold promoted the proliferation of hPDLCs and increased the expression levels of collagen I and scleraxis compared with PLGA scaffold. Animal experiments showed that more regular PDL-like tissues and less root surface resorption occurred in the PLGA/pFGF-2 scaffold group compared with the PLGA scaffold group. The PLGA/pFGF-2 scaffold promoted hPDLCs proliferation and facilitated periodontal ligament-related differentiation. The PLGA/pFGF-2 scaffold possesses excellent biological characteristics and could be used as a promising biomaterial for improving the treatment prognosis of replanted tooth.

The 3D-Printed PLGA Scaffolds Loaded with Bone Marrow-Derived Mesenchymal Stem Cells Augment the Healing of Rotator Cuff Repair in the Rabbits

The healing of tendon–bone in the rotator cuff is featured by the formation of the scar tissues in the interface after repair. This study aimed to determine if the 3D-printed poly lactic-co-glycolic acid (PLGA) scaffolds loaded with bone marrow-derived mesenchymal stem cells (BMSCs) could augment the rotator cuff repair in the rabbits. PLGA scaffolds were generated by the 3D-printed technology; Cell Counting Kit-8 assay evaluated the proliferation of BMSCs; the mRNA and protein expression levels were assessed by quantitative real-time polymerase chain reaction and western blot, respectively; immunohistology evaluated the rotator cuff repair; biomechanical characteristics of the repaired tissues were also assessed. 3D-printed PLGA scaffolds showed good biocompatibility without affecting the proliferative ability of BMSCs. BMSCs–PLGA scaffolds implantation enhanced the cell infiltration into the tendon-bone injunction at 4 weeks after implantation and improved the histology score in the tendon tissues after implantation. The mRNA expression levels of collagen I, III, tenascin, and biglycan were significantly higher in the scaffolds + BMSCs group at 4 weeks post-implantation than that in the scaffolds group. At 8 and 12 weeks after implantation, the biglycan mRNA expression level in the BMSCs–PLGA scaffolds group was significantly lower than that in the scaffolds group. BMSCs–PLGA scaffolds implantation enhanced collagen formation and increased collagen dimeter in the tendon–bone interface. The biomechanical analysis showed that BMSCs–PLGA scaffolds implantation improved the biomechanical properties of the regenerated tendon. The combination of 3D-printed PLGA scaffolds with BMSCs can augment the tendon–bone healing in the rabbit rotator cuff repair model.

E-Jet 3D-Printed Scaffolds as Sustained Multi-Drug Delivery Vehicles in Breast Cancer Therapy.

Combination chemotherapy is gradually receiving more attention because of its potential synergistic effect and reduced drug doses in clinical application. However, how to precisely control drug release dose and time using vehicles remains a challenge. This work developed an efficient drug delivery system to combat breast cancer, which can enhance drug effects despite reducing its concentration. Controlled-release poly-lactic-co-glycolic acid (PLGA) scaffolds were fabricated by E-jet 3D printing to deliver doxorubicin (DOX) and cisplatin (CDDP) simultaneously. This drug delivery system allowed the use of a reduced drug dosage resulting in a better effect on the human breast cancer cell apoptosis and inhibiting tumor growth, compared with the effect of each drug and the two drugs administrated without PLGA scaffolds. Our study suggested that DOX-CDDP-PLGA scaffolds could efficiently destroy MDA-MB-231 cells and restrain tumor growth. The 3D printed PLGA scaffolds with their time-programmed drug release might be useful as a new multi-drug delivery vehicle in cancer therapy, which has a potential advantage in a long term tumor cure and prevention of tumor recurrence.