PLLA Scaffolds Research Articles

PLLA scaffolds with controlled surface potential and piezoelectricity for enhancing cell adhesion in tissue engineering

The effect of the surface potential of biomaterials on cell attachment and development in regenerative medicine is still an unexplored area driving many regeneration processes, especially in piezoelectric bone tissue. Within this study, we electrospun poly(l-lactide) scaffolds constructed of fibers with either higher (−600 mV) or lower (−300 mV) surface potential, which is controlled by applied voltage polarity during their production. Interestingly, this way, the piezoelectric performance of PLLA fibers can be enhanced. The direct measurement of the PLLA fiber surface potential using Kelvin probe force microscopy (KPFM) showed a good correlation with the zeta potential analysis. The piezoelectricity of PLLA fibers was verified with piezoresponse force microscopy (PFM), indicating that it can be enhanced by applying the positive voltage polarity to the nozzle during electrospinning. Importantly, the cell adhesion assay showed a significant effect of the higher surface potential of PLLA fibers on osteoblasts behavior and creating a favorable bioelectric microenvironment. We observed enhanced initial adhesion of cells in the first 5 h with no additional effect of surface potential on proliferation, morphology, or collagen production. It was demonstrated that electrospun PLLA fibers with tunable surface potential and piezoelectricity are excellent for constructing bone tissue engineering scaffolds.

Characterization of 3D printed biodegradable piezoelectric scaffolds for bone regeneration.

The primary objective of this research was to develop a poly(l-lactic acid)(PLLA) scaffold and evaluate critical characteristics essential for its biologic use as a craniofacial implant. PLLAscaffolds were designed and fabricated using fused deposition modeling technology. The surface morphology and microarchitecture were analyzed using scanning electron microscopy (SEM) and microCT, respectively. Crystallography, compressive modulus, and the piezoelectric potential generated upon mechanical distortion were characterized. Hydrolytic degradation was studied. MG63 osteoblast-like cell proliferation and morphology were assessed. The porosity of the scaffolds was 73%, with an average pore size of 450 µm and an average scaffold fiber thickness of 130 µm. The average compressive modulus was 244 MPa, and the scaffolds generated an electric potential of 25 mV upon cyclic/repeated loading. The crystallinity reduced from 27.5% to 13.9% during the 3D printing process. The hydrolytic degradation was minimal during a 12-week period. Osteoblast-like cells did not attach to the uncoated scaffold but attached well after coating the scaffold with fibrinogen. They then proliferated to cover the complete scaffold by Day 14. The PLLA scaffolds were designed and printed, proving the feasibility of 3D printing as a method of fabricating PLLA scaffolds. The elastic modulus was comparable to that of trabecular bone, and the piezoelectric properties of the PLLA were retained after 3D printing. The scaffolds were cytocompatible. These 3D-printed PLLA scaffolds showed promising properties akin to the natural bone, and they warrant further investigation for bone regeneration.

Sequential Release of Panax Notoginseng Saponins and Osteopractic Total Flavone from Poly (L-Lactic Acid) Scaffold for Treating Glucocorticoid-Associated Osteonecrosis of Femoral Head.

Glucocorticoids inhibit angiogenesis in the femoral head, which fails to nourish the bone tissue and leads to osteonecrosis. Restoring angiogenesis is not only essential for vessel formation, but also crucial for osteogenesis. Poly (L-lactic acid) (PLLA) is commonly used in the bone tissue engineering field. Panax notoginseng saponins (PNS) and osteopractic total flavone (OTF) promote angiogenesis and osteogenesis, respectively. We designed a sequentially releasing PLLA scaffold including PLLA loaded with OTF (inner layer) and PLLA loaded with PNS (outer layer). We assessed the osteogenic effect of angiogenesis in this scaffold by comparing it with the one-layered scaffold (PLLA embedded with OTF and PNS) in vivo. Results from the micro-CT showed that the data of bone mineral density (BMD), bone volume (BV), and percent bone volume (BV/TV) in the PO-PP group were significantly higher than those in the POP group (p < 0.01). Histological analyses show that the PO-PP scaffold exhibits better angiogenic and osteogenic effects compared with the one-layered scaffold. These might result from the different structures between them, where the sequential release of a bi-layer scaffold achieves the osteogenic effect of vascularization by initially releasing PNS in the outer layer. We further explored the possible mechanism by an immunohistochemistry analysis and an immunofluorescence assay. The results showed that the protein expressions of vascular endothelial growth factor (VEGF) and platelet endothelial cell adhesion molecule-1(CD31) in the PO-PP scaffold were significantly higher than those in the POP scaffold (p < 0.01); the protein expressions of osteocalcin (OCN), osteopontin (OPN), and alkaline phosphatase (ALP) in the PO-PP scaffold were significantly higher than those in the POP scaffold (p < 0.05). Upregulating the expressions of angiogenic and osteogenic proteins might be the possible mechanism.

Engineering a wirelessly self-powered and electroconductive scaffold to promote peripheral nerve regeneration

Electroactive biomaterials have been shown useful for the repair of injured peripheral nerve. While for conventional conductive conduits, outer electrical stimulation device is unavoidably employed to exert electrical signals, and their rigid microstructures are usually incompatible with neural cells. Herein, a soft carbon nanotubes@gelatin methacryloyl/poly(L-lactic acid) (CNTs@GelMA/PLLA) nerve tissue-engineering scaffold was fabricated, which provided an endogenous piezoelectric stimulation and conductive microenvironment. Based on amounts of in-vitro experiment data, such composite scaffold significantly improved adhesion and elongation of Schwann cells, and meanwhile promoted axonal outgrowth and neurites number of dorsal root ganglions. More interestingly, the scaffold was applied to a 10-mm sciatic nerve defect in rats and harvested at 12 weeks post-implantation. Immunohistochemical staining results indicated that our proposed graft significantly facilitated peripheral nerve regeneration by promoting myelination and axon outgrowth, meanwhile an enhanced motor functional recovery caused by the scaffold was also revealed due to the obviously-improved sciatic functional index and muscle weights. Overall, the soft, self-powered, and electroconductive CNTs@GelMA/PLLA scaffold is a promising candidate for the treatment of peripheral nerve injuries.

Computational modeling and experimental characterization of fluid dynamics in micro-CT scanned scaffolds within a multiple-sample airlift perfusion bioreactor

The perfusion of flow during cell culture induces cell proliferation and enhances cellular activity. Perfusion bioreactors offer a controlled dynamic environment for reliable in vitro applications in the tissue engineering field. In this work, to evaluate the effects of the operating parameters of a custom-made bioreactor, numerical simulations were performed to solve the fluid velocity profile inside the bioreactor containing multi-grid support that allows allocating of multiple seeded scaffolds at the same time. The perfusion system exhibited a uniform distribution of liquid velocities within the regions, suitable for cell growth on seeded scaffolds. The effects of the porous microstructure of scaffolds on the extracellular matrix deposition also play a crucial role during perfusion cultures. In the present study, a numerical simulation was implemented at the pore level of the scaffold for fluid flow through porous media during perfused culture. Micro-computed tomography was used to obtain the digital 3D image of the complex geometry of a PLLA scaffold, offering a detailed analysis from a volume-based methodology without simplifications of the results as for pore or Darcy’s law-models. Predictions about the uniformity of the flow field through the scaffolds-bioreactor system have been assessed by quantifying the cell viability of a perfusion culture while using pre-osteoblastic cells seeded on 24 PLLA scaffolds for up to 6 days.

RhBMP-2-Conjugated Three-Dimensional-Printed Poly(L-lactide) Scaffold is an Effective Bone Substitute.

Bone growth factors, particularly bone morphogenic protein-2 (BMP-2), are required for effective treatment of significant bone loss. Despite the extensive development of bone substitutes, much remains to be desired for wider application in clinical settings. The currently available bone substitutes cannot sustain prolonged BMP-2 release and are inconvenient to use. In this study, we developed a ready-to-use bone substitute by sequential conjugation of BMP to a three-dimensional (3D) poly(L-lactide) (PLLA) scaffoldusing novel molecular adhesive materials that reduced the operation time and sustained prolonged BMP release. A 3D PLLA scaffold was printed and BMP-2 was conjugated with alginate-catechol and collagen. PLLA scaffolds were conjugated with different concentrations of BMP-2 and evaluated for bone regeneration in vitro and in vivo using a mouse calvarial model. The BMP-2 release kinetics were analyzed using ELISA. Histological analysis and micro-CT image analysis were performed to evaluate new bone formation. The 3D structure of the PLLA scaffold had a pore size of 400µm and grid thickness of 187-230µm. BMP-2 was released in an initial burst, followed by a sustained release for 14days. Released BMP-2 maintained osteoinductivity in vitro and in vivo. Micro-computed tomography and histological findings demonstrate that the PLLA scaffold conjugated with 2µg/ml of BMP-2 induced optimal bone regeneration. The 3D-printed PLLA scaffold conjugated with BMP-2 enhanced bone regeneration, demonstrating its potential as a novel bone substitute.

Nanonodular porous membranes: Novel scaffolds for development and proliferation of dental pulp‐derived mesenchymal stem cells

AbstractScaffolds have similar functions to the extracellular matrix and are an important component of tissue engineering techniques. Poly(l‐lactic acid) (PLLA) is one of the scaffolding materials used in this field. The aim of this study was to investigate the biocompatibility and effect of novel PLLA scaffolds on mesenchymal stem cell (MSC) proliferation. PLLA scaffolds in this study were nanonodular porous membranes which were prepared by phase separation process. Dental pulp‐derived MSCs were cultured on nanonodular membrane scaffolds and cell vitality and proliferation was evaluated over a 2‐week period using MMT test on days 5, 7, and 9. Also, ultrastructure and adhesion of MSCs to these novel PLLA nanonodular porous membranes using field‐emission‐scanning electron microscopy (FE‐SEM) was assessed. The biocompatibility of nanonodular membrane scaffolds was good and the cells adhered well to the membrane surface. The viability of MSCs in the samples with the nanonodular membrane scaffolds was significantly higher than the group without the membrane scaffolds. The highest effect of PLLA nanonodular membrane scaffolds on cell vitality was observed on the ninth day and the least effect was observed on the 5th day. Due to its biodegradability and lack of toxicity, PLLA nanonodular membrane scaffolds increased the rate of adhesion and proliferation of MSCs and this process intensified over time.

Bone ECM-like 3D Printing Scaffold with Liquid Crystalline and Viscoelastic Microenvironment for Bone Regeneration.

Implanting a 3D printing scaffold is an effective therapeutic strategy for personalized bone repair. As the key factor for the success of bone tissue engineering, the scaffold should provide an appropriate bone regeneration microenvironment and excellent mechanical properties. In fact, the most ideal osteogenic microenvironment is undoubtedly provided by natural bone extracellular matrix (ECM), which exhibits liquid crystalline and viscoelastic characteristics. However, mimicking a bone ECM-like microenvironment in a 3D structure with outstanding mechanical properties is a huge challenge. Herein, we develop a facile approach to fabricate a bionic scaffold perfectly combining bone ECM-like microenvironment and robust mechanical properties. Creatively, 3D printing a poly(l-lactide) (PLLA) scaffold was effectively strengthened via layer-by-layer electrostatic self-assembly of chitin whiskers. More importantly, a kind of chitin whisker/chitosan composite hydrogel with bone ECM-like liquid crystalline state and viscoelasticity was infused into the robust PLLA scaffold to build the bone ECM-like microenvironment in 3D structure, thus highly promoting bone regeneration. Moreover, deferoxamine, an angiogenic factor, was encapsulated in the composite hydrogel and sustainably released, playing a long-term role in angiogenesis and thereby further promoting osteogenesis. This scaffold with bone ECM-like microenvironment and excellent mechanical properties can be considered as an effective implantation for bone repair.

Biomimetic mineralization of poly(L-lactic acid) nanofibrous microspheres for bone regeneration

Simulating the hierarchical structure of natural bone, mineralized synthetic polymer fibrils such as poly(L-lactic acid) (PLLA) in the form of microspheres show considerable potential as injectable scaffolds for bone defect repair. However, the hydrophobicity of PLLA restricts the deposition of bone-like apatite on the surface of PLLA directly, limiting its application in osteogenesis. In this paper, after sodium trimetaphosphate (STMP) modification, nanofibrous PLLA microspheres were immersed into 2.5 times simulated body fluid (2.5×SBF) for 3 days to produce abundant bone-like apatite on the surface of microspheres. The bioactivity in vitro and bone repair ability in vivo of surface mineralized PLLA microspheres were evaluated. The results indicated that surface mineralized nanofibrous PLLA microspheres improved MSCs proliferation and bone-related gene expression, including OPN, RUNX-2 and OCN. After the surface mineralized nanofibrous PLLA microspheres were implanted into rat skulls to repair bone defects (5 mm) for 6 weeks, the micro-CT and histology results showed that the surface mineralized nanofibrous PLLA microspheres improved bone regeneration compared to pure nanofibrous PLLA microspheres. Our study provides a feasible strategy for the rapid preparation of biomimetic mineralized PLLA scaffolds, the novel mineralized microspheres showed considerable bone repair potential.

The Performance of Nonwoven PLLA Scaffolds of Different Thickness for Stem Cells Seeding and Implantation.

The 3D reconstruction of 100 μm- and 600 μm-thick fibrous poly-L/L-lactide scaffolds was performed by confocal laser scanning microscopy and supported by scanning electron microscopy and showed that the density of the fibers on the side adjacent to the electrode is higher, which can affect cell diffusion, while the pore size is generally the same. Bone marrow mesenchymal stem cells cultured in a 600 μm-thick scaffold formed colonies and produced conditions for cell differentiation. An in vitro study of stem cells after 7 days revealed that cell proliferation and hepatocyte growth factor release in the 600 μm-thick scaffold were higher than in the 100 μm-thick scaffold. An in vivo study of scaffolds with and without stem cells implanted subcutaneously onto the backs of recipient mice was carried out to test their biodegradation and biocompatibility over a 0–3-week period. The cells seeded onto the 600 μm-thick scaffold promoted significant neovascularization in vivo. After 3 weeks, a significant number of donor cells persisted only on the inside of the 600 μm-thick scaffold. Thus, the use of bulkier matrices allows to prolong the effect of secretion of growth factors by stem cells during implantation. These 600 μm-thick scaffolds could potentially be utilized to repair and regenerate injuries with stem cell co-culture for vascularization of implant.

Synergistic Effect of Reinforced Multiwalled Carbon Nanotubes and Boron Nitride Nanosheet-Based Hybrid Piezoelectric PLLA Scaffold for Efficient Bone Tissue Regeneration.

Electrospun poly(l-lactic acid) nanofibers (PLLANFs) have been receiving considerable attention in bone tissue engineering (BTE) due to their tunable biodegradability and remarkable in vitro and in vivo biocompatibility. However, deterioration in the mechanical strength of PLLANFs during the regeneration process leads to low osteoinductive performances. Additionally, their high hydrophobicity and limited piezoelectric properties have to be addressed concerning BTE. Herein, we report an efficient approach for fabricating high-performance PLLANF hybrid scaffolds for BTE by reinforcing amphiphilic triblock copolymer pluronic F-127 (PL)-functionalized nanofillers (PL-functionalized carboxylated multiwalled carbon nanotubes (PL-cMWCNTs) and PL-functionalized exfoliated boron nitride nanosheets (PL-EBN)). The synergistic reinforcement effect from one-dimensional (1D) electrically conducting PL-cMWCNTs and two-dimensional (2D) piezoelectric PL-EBN was remarkable in PLLANFs, and the obtained PL-Hybrid (PL-cMWCNTs + PL-EBN) reinforced scaffolds have outperformed the mechanical strength, wettability, and piezoelectric performances of pristine PLLANFs. Consequently, in vitro biocompatibility results reveal the enhanced proliferation of MC3T3-E1 cells on PL-Hybrid nanofiber scaffolds. Furthermore, the ALP activity, ARS staining, and comparable osteogenic gene expression results demonstrated significant osteogenic differentiation of MC3T3-E1 cells on PL-Hybrid nanofiber scaffolds than on the pristine PLLANF scaffold. Thus, the reported approach for constructing high-performance piezoelectric biodegradable scaffolds for BTE by the synergistic effect of PL-cMWCNTs and PL-EBN holds great promise in tissue engineering applications.

The effect of blending poly (l-lactic acid) on in vivo performance of 3D-printed poly(l-lactide-co-caprolactone)/PLLA scaffolds.

Blending poly (l-lactic acid, PLLA) with poly (l-lactide-co-caprolactone, PLCL) is an effective strategy for developing new PLCL/PLLA blend based biomaterials. However, the effect of PLLA on in vivo performance of PLCL/PLLA blends is unclear yet. To address this issue, in this study, the effect of PLLA on in vivo biodegradability and biocompatibility of 3D-printed scaffolds of PLCL/PLLA blend was investigated. Three kinds of different 3D-printed PLCL/PLLA scaffolds using different blends with different mass ratios of the polymers, were prepared and implanted subcutaneously. The shrinkage and tissue responses were monitored by ultrasonography after the implantation. 2months post-operation, the in vivo performances of the scaffolds were investigated histologically. All scaffolds showed good biocompatibility and allowed fast tissues ingrowth, however PLCL50/PLLA50 scaffold with the highest PLLA ratio induced the thickest the fibrous capsule surrounding the scaffolds and highest inflammatory scores. Furthermore, it was found that the fine porous structures of all scaffolds were well maintained, indicating the 3D-printed scaffolds were degraded through a surface erosion but not bulk erosion way. However, different scaffolds showed different shrinkage and degradation ratios, and PLCL50/PLLA50 scaffold resulted in a significant shrinkage, while PLCL90/PLLA10 scaffold showed the better structural stability. Therefore, PLLA at blending different ratio had different effects on the in vivo performance of 3D-printed PLCL/PLLA scaffolds. Particularly, PLCL/PLLA scaffolds blending with low ratio of PLLA, such as PLCL90/PLLA10 scaffold showed better application potential in tissue engineering. Our findings provide a new insight on the rational design, constrcution and application of the 3D-printed PLCL/PLLA scaffolds.

Surface modification of PLLA scaffolds via reactive magnetron sputtering in mixtures of nitrogen with noble gases for higher cell adhesion and proliferation

Despite the widespread use of bioresorbable electrospun poly-L-lactic acid scaffolds in tissue engineering, a significant drawback is the high hydrophobicity of their surface. A proper solution for this problem is the surface modification with titanium oxynitride coatings using reactive magnetron sputtering. However, this method is characterized by a low deposition rate and the difficult selection of suitable working parameters. A feasible solution to this problem is the addition of a noble gas to the working gas nitrogen, which increases the deposition rate and thus the coating thicknesses, even with gentle magnetron sputtering process parameters. In this study, the results of surface modification of poly-L-lactic acid scaffolds using direct current reactive magnetron sputtering of a titanium target in the presence of a mixture of the working gas nitrogen with one of the following noble gases: helium, neon, argon, krypton, and xenon. Due to this modification, depending on the composition of the gas mixture, a thin nitrogen-containing titanium coating forms on the scaffold surface, represented by titanium oxide and titanium oxynitrides of different stoichiometry. At the same time, the modification process does not significantly affect the morphology, crystallinity and molecular conformation of the poly-L-lactic acid scaffold backbones, while an increase in the surface wettability is observed. Another biomedical important effect of this surface modification is an observed increase in the adhesion and proliferative activity of fibroblast culture applied to the investigated poly-L-lactic acid scaffold samples. The poly-L-lactic acid scaffold samples surface-modified via direct current reactive magnetron sputtering of a titanium target in a mixture of the working gas nitrogen and the noble gas argon shows the highest number of adhered fibroblasts.

Melt-Electrowritten Poly(L-lactic acid)- and Bioglass-Reinforced biomimetic hydrogel for bone regeneration

High-precision poly(L-lactic acid) (PLLA) scaffold fabricated by melt electrowriting (MEW) as a bone substitute was investigated, however, the inherent fragility and the low bioactivity of the scaffold impede its clinical application. In this context, a biomimetic reinforced composite scaffold combining the MEW PLLA lattice with gelatin/genipin/bioglass hydrogel is firstly proposed. Incorporating with 1 wt% bioglass, the composite scaffold shows excellent interconnectivity, high storage modulus (121.3 kPa, 1.3 times of gelatin/genipin) and improved storage modulus (422.3 kPa). Moreover, this reinforced scaffold displays elevated in vitro osteoinduction/conduction capability, high amount of bone tissue formation and a prime Ca/P ratio of 1.69 (as compared with natural bone with Ca/P ratio of 1.67). The mechanisms of the enhanced mechanical properties and the variation of bone formation ability of various scaffolds are elucidated by a potential model. This study gives insights into some potential innovative strategies for using MEW PLLA scaffold to achieve unprecedented results in bone regeneration.

Hybrid electrospun scaffolds based on polylactic acid/ PAMAM dendrimer/gemini surfactant for enhancement of synergistic antibacterial ability for biomedical application

Hybrid electrospun scaffolds based on poly (L-lactic acid) (PLLA)/poly (amidoamine) (PAMAM-G2) dendrimer/gemini surfactant were fabricated for the enhancement of synergistic antibacterial activities. The second generation of poly (amidoamine) (PAMAM-G2) and cationic gemini surfactant were utilized to functionalize the optimum electrospun scaffolds. The gelatination process was utilized to improve the wettability of PLLA scaffolds to extend cell attachment and cell proliferation. PLLA nanofibrous scaffolds were characterized by energy dispersion x-ray, scanning electron microscopy images, mechanical properties, water contact angle, Fourier transform infrared spectroscopy, zeta potential and antibacterial assessment. In vitro cell biocompatibility was evaluated by 3-(4, 5- dimethylthiazoyl-2-yl)-2, 5-diphenyltetrazolium bromide assay and morphology of PC-12 cells cultured on hybrid nanofibrous scaffolds and gelatinized ones. The results indicated that the optimum scaffolds could successfully modify the characteristics of PLLA scaffolds leading to much more appropriate physical and chemical properties. In addition, gelatinized nanofibrous scaffolds reveal more wettability enhancing cell attachment and proliferation. Furthermore, using poly (amidoamine) (PAMAM-G2) and gemini surfactant reveals synergetic antibacterial activity due to the competition between both cationic groups of PAMAM and gemini surfactant. Finally, improved cell adhesion and cell viability on modified scaffolds were confirmed. These favorable properties give a chance for these scaffolds to be used in a wide variety of biomedical applications.

Dual surface modification of poly(L-lactide) scaffold achieved by thermal incorporation of aligned nanofiber and click immobilization of VEGF to enhance endothelialization and blood compatibility

Rapid endothelialization is very important in the development of blood-contact biomaterials because of the inhibitory effects of endothelium in preventing thrombosis and restenosis. In this study, topographical and biochemical cues were generated to accelerate endothelialization on the poly(L-lactide) (PLLA) scaffold via a simple, bio-orthogonal, and biocompatible process. Topographical guidance was incorporated into a PLLA scaffold via thermal attachment of aligned PLLA nanofibers using electrospinning. Vascular endothelial growth factor (VEGF) was covalently immobilized onto the PLLA scaffold by aminolysis and copper-catalyzed azide/alkyne cycloaddition-mediated click chemistry. Various surface analyses confirmed the presence of aligned topography and immobilized VEGF without delamination or leaching. In vitro experiments with human coronary artery endothelial cells revealed that proliferation, CD31 expression, and migration was significantly enhanced on the nanofiber-attached VEGF-immobilized PLLA scaffold. The aligned nanofiber also accommodated the sustained release of heparin, which suppressed the proliferation of human coronary artery smooth muscle cells and platelet activation without affecting surface endothelialization. The heparin-loaded, aligned, nanofiber-attached VEGF-immobilized PLLA scaffold was evidenced to be biocompatible and a promising candidate for blood-contact materials where fast endothelialization and suppressed platelet activation is required.

Enhancing the bioactivity of melt electrowritten PLLA scaffold by convenient, green, and effective hydrophilic surface modification

As an emerging additive manufacturing (AM) technique, melt electrospinning writing (MEW) is used to fabricate three-dimensional (3D) submicron filament-based scaffolds with adjustable pore size and customized structure for bone regeneration. Poly(L-lactic acid) (PLLA) scaffold with excellent biodegradability and biocompatibility is first successfully manufactured using our self-assembled MEW device. However, the ultralow cell affinity and poor bioactivity severely hamper their practical applications in bone tissue engineering. These issues are caused by the severe inherent biologically inert, hydrophobicity as well as the smooth surface of the MEW PLLA filaments. In this study, a green and robust alkaline method is applied to modify the scaffold surface and to improve the bioactivity of the MEW PLLA scaffold. Without deterioration in mechanical property but robust surface hydrophilicity, the optimal MEW PLLA scaffold shows promoted surface roughness, enhanced filament tensile modulus (~ 2 folds of the as-prepared sample), and boosted crystallizability (ultrahigh WAXD intensity). Moreover, after being cultured with KUSA-A1 cells, the 0.5 M NaOH, 2 h treated MEW PLLA scaffold exhibits higher osteoinductive ability and increased immature bone tissue amounts (3 times of controlled scaffold). Thus, the flexible surface functionalization by the specific alkaline treatment was found to be an effective method for the preparation of bioactivated MEW PLLA scaffolds with promoted bone regeneration.

Reactive Magnetron Plasma Modification of Electrospun PLLA Scaffolds with Incorporated Chloramphenicol for Controlled Drug Release.

Surface modification with the plasma of the direct current reactive magnetron sputtering has demonstrated its efficacy as a tool for enhancing the biocompatibility of polymeric electrospun scaffolds. Improvement of the surface wettability of materials with water, as well as the formation of active chemical bonds in the near-surface layers, are the main reasons for the described effect. These surface effects are also known to increase the release rate of drugs incorporated in fibers. Herein, we investigated the effect of plasma modification on the chloramphenicol release from electrospun poly (lactic acid) fibrous scaffolds. Scaffolds with high—50 wt./wt.%—drug content were obtained. It was shown that plasma modification leads to an increase in the drug release rate and drug diffusion coefficient, while not deteriorating surface morphology and mechanical properties of scaffolds. The materials’ antibacterial activity was observed to increase in the first day of the experiment, while remaining on the same level as the unmodified group during the next six days. The proposed technique for modifying the surface of scaffolds will be useful for obtaining drug delivery systems with controlled accelerated release, which can expand the possibilities of local applications of antibiotics and other drugs.

Exercise-induced piezoelectric stimulation for cartilage regeneration in rabbits.

More than 32.5 million American adults suffer from osteoarthritis, and current treatments including pain medicines and anti-inflammatory drugs only alleviate symptoms but do not cure the disease. Here, we have demonstrated that a biodegradable piezoelectric poly(L-lactic acid) (PLLA) nanofiber scaffold under applied force or joint load could act as a battery-less electrical stimulator to promote chondrogenesis and cartilage regeneration. The PLLA scaffold under applied force or joint load generated a controllable piezoelectric charge, which promoted extracellular protein adsorption, facilitated cell migration or recruitment, induced endogenous TGF-β via calcium signaling pathway, and improved chondrogenesis and cartilage regeneration both in vitro and in vivo. Rabbits with critical-sized osteochondral defects receiving the piezoelectric scaffold and exercise treatment experienced hyaline-cartilage regeneration and completely healed cartilage with abundant chondrocytes and type II collagen after 1 to 2 months of exercise (2 to 3 months after surgery including 1 month of recovery before exercise), whereas rabbits treated with nonpiezoelectric scaffold and exercise treatment had unfilled defect and limited healing. The approach of combining biodegradable piezoelectric tissue scaffolds with controlled mechanical activation (via physical exercise) may therefore be useful for the treatment of osteoarthritis and is potentially applicable to regenerating other injured tissues.

Design and manufacturing of 3D high-precision micro-fibrous poly (l-lactic acid) scaffold using melt electrowriting technique for bone tissue engineering

The thermally sensitive polymer, poly (l-lactic acid) PLLA, is first printed to a high-resolution object using an advanced 3D printing technology, called melt electrowriting (MEW). The MEW processing conditions are systematically investigated to manufacture PLLA scaffolds with adjustable filament diameter and pore size for the application of bone tissue engineering. To this end, the relationships among the rheological behavior of the molten polymer, the electro-hydrodynamics of the jet, and the processing parameters (applied voltage, collection speed, and flow rate) are illuminated. The scaffold with relatively high deposition accuracy and crystallinity of PLLA is achieved when the printing speed was set slightly above the critical translation speed. The MEW PLLA scaffold with filament diameter of 40 μm and pore size of 200 μm is evaluated with KUSA-A1 cells to prove its in vitro potential. This is a milestone work for MEW since it supplies one of the best strategies to design and manufacture an essential biobased polymer for tissue engineering.