Category Archives: Tissue Engineering/Scaffolds

Category applies to the use of polymers towards tissue engineering of a variety of tissues including serving as cell scaffolds or delivery systems for stem-cells/active ingrediants for repairing tissue defects.

PLGA-diol precursor from PolySciTech used in biodegradable polyurethane development

PolySciTech Division of Akina, Inc. (www.polyscitech.com) provides a wide variety of research polymers. This includes PLGA di-alcohol precursors such as HO-PLGA-TEG-PLGA-OH (Polyvivo AK076). The dialcohol units on these polymers can react with isocyanate groups to form urethane linkages. Since the polymer is difunctionalized, it joins into the forming chain of a polyurethane and acts as a chain extender linked di-isocyanates together. Although typical polyurethanes are not biodegradable, the incorporation of PLGA into the polyurethane backbone in this way renders the polymer as a degradable matrix useful for a wide array of applications. Read more about this exciting technology here: Blakney, Anna K., Felix Simonovsky, Ian T. Suydam, Buddy D. Ratner, and Kim A. Woodrow. . “Rapidly Biodegrading PLGA-Polyurethane Fibers for Sustained Release of Physicochemically Diverse Drugs”. ACS Biomaterials Science & Engineering 2016 (http://pubs.acs.org/doi/abs/10.1021/acsbiomaterials.6b00346)

“Abstract: Sustained release of physicochemically diverse drugs from electrospun fibers remains a challenge and precludes the use of fibers in many medical applications. Here we synthesize a new class of polyurethanes with PLGA moieties that degrade faster than polyurethanes based on polycaprolactone. The new polymers, with varying hard to soft segment ratios and fluorobenzene pendant group content, were electrospun into nanofibers and loaded with four topically relevant but physicochemically diverse small molecule drugs. Polymers were characterized using GPC, XPS and 19F NMR. The size and morphology of electrospun fibers were visualized using SEM, and drug/polymer compatibility and drug crystallinity were evaluated using DSC. We measured the in vitro release of physicochemically diverse drugs, and polymer degradation and cytotoxicity of biodegradation products were evaluated in cell culture. We show that these newly synthesized PLGA-based polyurethanes degrade up to 65-80% within four weeks, and are cytocompatible in vitro. The resulting drug-loaded electrospun fibers were amorphous solid dispersions. We found that increasing the hard to soft segment ratio of the polymer enhances the sustained release of positively charged drugs, while increasing the fluorobenzene pendant content caused more rapid release of some drugs. Increasing the hard segment or fluorobenzene pendant content of segmented polyurethanes containing PLGA moieties allows for modulation of physicochemically diverse drug release from electrospun fibers, while maintaining a biologically relevant biodegradation rate.”

Diacrylated biodegradable copolymers for photo-initiated 3D printing available from PolySciTech

PolySciTech division of Akina, Inc (www.polyscitech.com) provides a wide array of biodegradable polymers including vinyl modified block copolymers which can be used as macromers. Examples of this include PLGA-PEG-PLGA-diacrylate, PLA-diacrylate, and others available through our reactive intermediate series (PolyVivo AI***). These polymers can be dissolved in an appropriate solvent or blended in a melt along with an appropriate photo-initiator (Irgacure or other) and 3D printed under illuminated conditions to create a chemically crosslinked structure. This soft-printing technique at low temperature conditions allows for the potential of printing living cells or other biologics directly into the printed matrix.  Historically, researchers have been limited to very few commercially available magromers, such as poly(ethylene glycol) diacrylate, for this application. This macromere prints well but has limited cell interaction and poorly controlled degradability. The use of biodegradable macromers with polyester blocks can allow for more controlled degradability. A recent review article highlights the potential for printing living cells. Read more: Park, Jeong Hun, Jinah Jang, Jung-Seob Lee, and Dong-Woo Cho. “Three-Dimensional Printing of Tissue/Organ Analogues Containing Living Cells.” Annals of biomedical engineering (2016): 1-15. http://link.springer.com/article/10.1007/s10439-016-1611-9

“Abstract: The technical advances of three-dimensional (3D) printing in the field of tissue engineering have enabled the creation of 3D living tissue/organ analogues. Diverse 3D tissue/organ printing techniques with computer-aided systems have been developed and used to dispose living cells together with biomaterials and supporting biochemicals as pre-designed 3D tissue/organ models. Furthermore, recent advances in bio-inks, which are printable hydrogels with living cell encapsulation, have greatly enhanced the versatility of 3D tissue/organ printing. Here, we introduce 3D tissue/organ printing techniques and biomaterials that have been developed and widely used thus far. We also review a variety of applications in an attempt to repair or replace the damaged or defective tissue/organ, and develop the in vitro tissue/organ models. The potential challenges are finally discussed from the technical perspective of 3D tissue/organ printing. Keywords: 3D tissue/organ printing Bio-inks 3D tissue/organ analogues Tissue engineering and regenerative medicine 3D in vitro tissue/organ models.”

PLGA from PolySciTech investigated for in-situ delivery of doxorubicin for treatment of liver cancer

PolySciTech division of Akina, Inc (www.polyscitech.com) provides a wide array of biodegradable block copolymers and polyesters. This includes PLGA (PolyVivo AP031) which has recently been used in a study relating to localized delivery of doxorubicin to a tumor site. There are many advantages to providing localized delivery, especially for chemotherapeutics, as this reduces systemic toxicity to whole body while maintaining a therapeutic concentration directly at the tumor site. One means of doing this is to dissolve a biodegradable polymer (such as PLGA) in a water-miscible, biocompatible organic solvent such as N-methyl-2-pyrrolidinone (NMP) along with the drug to be delivered. When this solution is introduced into the body, the NMP extracts out quickly with the surrounding bodily fluids leaving a solid PLGA form containing the drug. This is referred to as an ‘in-situ implant’ because the solid implant is actually formed inside the body itself. From this point forward, the drug leaches slowly out of the PLGA by diffusion and degradation, providing an extended delivery system which provides drug directly to the local tissues. A major advantage to using this system is direct, local application of the medicine. This is unlike systemic application. The majority of medicine which is administered systemically (for example, a traditional IV injection) never reaches the location of action. Instead, the body’s natural screening mechanisms, remove the drug from the blood by the kidneys and it ends up in the urine, or it is removed by other pathways.  Recently, researchers used in-situ formation technique to deliver PLGA encapsulated doxorubicin to model liver-cancer tumors. Liver cancer is normally resistant to traditional chemotherapy. They found that the tumors had significantly reduced progression after 21 days from this doxorubicin delivery method which holds promise as a treatment method. Read more: Solorio, Luis, Hanping Wu, Christopher Hernandez, Mihika Gangolli, and Agata A. Exner. “Ultrasound-guided intratumoral delivery of doxorubicin from in situ forming implants in a hepatocellular carcinoma model.” Therapeutic Delivery 7, no. 4 (2016): 201-212. http://www.future-science.com/doi/abs/10.4155/tde-2015-0008

“Abstract: Background: Hepatocellular carcinomas are frequently nonresponsive to systemically delivered drugs. Local delivery provides an alternative to systemic administration, maximizing the dose delivered to the tumor, achieving sustained elevated concentrations of the drug, while minimizing systemic exposure. Results: Ultrasound-guided deposition of doxorubicin (Dox)-eluting in situ forming implants (ISFI) in an orthotopic tumor model significantly lowers systemic drug levels. As much as 60 µg Dox/g tumors were observed 21 days after ISFI injection. Tumors treated with Dox implants also showed a considerable reduction in progression at 21 days. Conclusion: Dox-eluting ISFIs provide a promising platform for the treatment of hepatocellular carcinomas by which drug can be delivered directly into the lesion, bypassing distribution and elimination by the circulatory system.”

Akina launches NanoMyP Polymblend product

In addition to in-house generated materials, PolySciTech division of Akina, Inc. (www.polyscitech.com) also distributes research products for a variety of applications.  Our most recent product launch is PolymBlend from NanoMyP of which Akina is the USA distributor. PolymBlend is optimized for electrospinning applications to form a non-woven mesh. Due to its unique properties, it has high tensile strength and alcohol units available along the polymer backbone allowing for chemical modifications. Find out more at our site https://akinainc.com/polyscitech/products/polymblend/index.php You can read more about this product’s research usage in a recent publication from the University of Granada here Orriach-Fernández, F. J., A. L. Medina-Castillo, J. E. Díaz-Gómez, A. Muñoz de la Peña, J. F. Fernández-Sánchez, and A. Fernández-Gutiérrez. “A sensing microfibre mat produced by electrospinning for the turn-on luminescence determination of Hg 2+ in water samples.” Sensors and Actuators B: Chemical 195 (2014): 8-14. (http://www.sciencedirect.com/science/article/pii/S0925400514000197)

“Abstract: A novel turn-on fluorescent microfibre mat with high selectivity towards Hg2+ has been prepared for determining and quantifying Hg2+ in water samples. It is based on the use of electrospinning for encapsulating a spirocyclic Rhodamine 6G phenyl-thiosemicarbazide derivative (called FC1) into polymeric microfibres and the well-known spirolactam (non fluorescent) to ring opened amine (fluorescent) equilibrium of Rhodamine derivatives as recognition mechanism. The fluorescence intensity was proportional to Hg2+ concentration in a linear range from 0.4 to 4.0 μM with a detection limit (S/N = 3) of 0.1 μM. Keywords: Optical sensor; Hg2+; Water analysis; Electrospinning; Rhodamine derivative”

PCL-PEG electrospun mesh investigated for scaffold treatment of damaged periodontal ligament

PolySciTech Division of Akina, Inc. (www.polyscitech.com) provides a wide array of block copolymers including PCL-PEG copolymers. One means of processing these polymers is using electrospinning. Electrospinning is a manufacturing technique based on applying a highly charged polymer solution onto a grounded metal collector. When this is done under the right conditions the polymer forms into an open mesh similar to woven fabric but with no particular weave pattern hence it is sometimes refered to as ‘non-woven.’ All the empty spaces in the micron scale work well for cell-permeation and so this is a popular technique for generating a tissue scaffold to help with guided tissue regeneration (GTR). The drawback to this technique is that the scaffold is somewhat generic and does not typically serve for regrowth of tissue which has a particular orientation to it. For example, the periodontal ligament tissue, which connects the jaw-bone to the root surface of teeth must be formed in a particular arrangement for it to hold everything in place the way it should. Recently, researchers electrospun PCL-PEG-PCL triblock polymer into sheets and then compressed together with a chitosan based ‘glue’ to form a tissue scaffold. This scaffold worked well to regenerate this oriented tissue both in-vitro and in vivo. Read more: Jiang, Wenlu, Long Li, Ding Zhang, Shishu Huang, Zheng Jing, Yeke Wu, Zhihe Zhao, Lixing Zhao, and Shaobing Zhou. “Incorporation of aligned PCL–PEG nanofibers into porous chitosan scaffolds improved the orientation of collagen fibers in regenerated periodontium.” Acta biomaterialia 25 (2015): 240-252. http://www.sciencedirect.com/science/article/pii/S1742706115300210

“Abstract: The periodontal ligament (PDL) is a group of highly aligned and organized connective tissue fibers that intervenes between the root surface and the alveolar bone. The unique architecture is essential for the specific physiological functionalities of periodontium. The regeneration of periodontium has been extensively studied by researchers, but very few of them pay attention to the alignment of PDL fibers as well as its functionalities. In this study, we fabricated a three-dimensional multilayered scaffold by embedding highly aligned biodegradable poly (ε-caprolactone)-poly(ethylene glycol) (PCE) copolymer electrospun nanofibrous mats into porous chitosan (CHI) to provide topographic cues and guide the oriented regeneration of periodontal tissue. In vitro, compared with random group and porous control, aligned nanofibers embedded scaffold could guide oriented arrangement and elongation of cells with promoted infiltration, viability and increased periodontal ligament-related genes expression. In vivo, aligned nanofibers embedded scaffold showed more organized arrangement of regenerated PDL nearly perpendicular against the root surface with more extensive formation of mature collagen fibers than random group and porous control. Moreover, higher expression level of periostin and more significant formation of tooth-supporting mineralized tissue were presented in the regenerated periodontium of aligned scaffold group. Incorporation of aligned PCE nanofibers into porous CHI proved to be applicable for oriented regeneration of periodontium, which might be further utilized in regeneration of a wide variety of human tissues with a specialized direction. Statement of Significance: The regeneration of periodontium has been extensively studied by researchers, but very few of them give attention to the alignment of periodontal ligament (PDL) fibers as well as its functionalities. The key issue is to provide guidance to the orientation of cells with aligned arrangement of collagen fibers perpendicular against the root surface. This study aimed to promote oriented regeneration of periodontium by structural mimicking of scaffolds. The in vitro and in vivo performances of the scaffolds were further evaluated to test the topographic-guiding and periodontium healing potentials. We also think our research may provide ideas in regeneration of a wide variety of human tissues with a specialized direction. Keywords: Periodontal tissue engineering; Biomimetics; Electrospun scaffold; Oriented regeneration; Periodontal ligament”

PLLA from PolySciTech used for bone scaffold application research

PolySciTech division of Akina, Inc (www.polyscitech.com) provides a wide array of biodegradable polymers including poly(L)lactide (PLLA). This is a highly crystalline and mechanically strong polymer which has good properties for load-bearing applications such as bone scaffolds. Recently, researchers combined PLLA from Polyscitech with hydroxyapatite to form a conventional bone-scaffold and tested against a novel N-methyldiethanolamine/poly(1,8-octanediol citrate) based scaffold. Read more: Tang, Jiajun, Jinshan Guo, Zhen Li, Cheng Yang, Denghui Xie, Jian Chen, Shengfa Li et al. “A fast degradable citrate-based bone scaffold promotes spinal fusion.” Journal of Materials Chemistry B 3, no. 27 (2015): 5569-5576. http://pubs.rsc.org/en/content/articlehtml/2015/tb/c5tb00607d

“Abstract: It is well known that high rates of fusion failure and pseudoarthrosis development (5–35%) are concomitant in spinal fusion surgery, which was ascribed to the shortage of suitable materials for bone regeneration. Citrate was recently recognized to play an indispensable role in enhancing osteoconductivity and osteoinductivity, and promoting bone formation. To address the material challenges in spinal fusion surgery, we have synthesized mechanically robust and fast degrading citrate-based polymers by incorporating N-methyldiethanolamine (MDEA) into clickable poly(1,8-octanediol citrates) (POC-click), referred to as POC-M-click. The obtained POC-M-click were fabricated into POC-M-click–HA matchstick scaffolds by forming composites with hydroxyapatite (HA) for interbody spinal fusion in a rabbit model. Spinal fusion was analyzed by radiography, manual palpation, biomechanical testing, and histological evaluation. At 4 and 8 weeks post surgery, POC-M-click–HA scaffolds showed optimal degradation rates that facilitated faster new bone formation and higher spinal fusion rates (11.2 ± 3.7, 80 ± 4.5 at week 4 and 8, respectively) than the poly(L-lactic acid)–HA (PLLA–HA) control group (9.3 ± 2.4 and 71.1 ± 4.4) (p < 0.05). The POC-M-click–HA scaffold-fused vertebrates possessed a maximum load and stiffness of 880.8 ± 14.5 N and 843.2 ± 22.4 N mm−1, respectively, which were also much higher than those of the PLLA–HA group (maximum: 712.0 ± 37.5 N, stiffness: 622.5 ± 28.4 N mm−1, p < 0.05). Overall, the results suggest that POC-M-click–HA scaffolds could potentially serve as promising bone grafts for spinal fusion applications.”

3D tumor spheroids more accurate model for cancer research than conventional 2D

In addition to polymer products, Akina, Inc. also offers thermogelling matrices for growth of cells in 3-dimensional structures under the brand-name 3DCellMaker (www.3dcellmaker.com). 3D tumor models present many advantages over 2D models in that they accurately represent in-vivo cancer conditions such as microenvironment parameters and cell-cell interactions. This makes these models more reliable in terms of predicting whether a therapeutic strategy will actually be effective in the clinic. Read more: Fitzgerald, Kathleen A., Meenakshi Malhotra, Caroline M. Curtin, Fergal J. O’Brien, and Caitriona M. O’Driscoll. “Life in 3D is never flat: 3D models to optimise drug delivery.” Journal of Controlled Release 215 (2015): 39-54. http://www.sciencedirect.com/science/article/pii/S016836591530033X

“Abstract: The development of safe, effective and patient-acceptable drug products is an expensive and lengthy process and the risk of failure at different stages of the development life-cycle is high. Improved biopharmaceutical tools which are robust, easy to use and accurately predict the in vivo response are urgently required to help address these issues. In this review the advantages and challenges of in vitro 3D versus 2D cell culture models will be discussed in terms of evaluating new drug products at the pre-clinical development stage. Examples of models with a 3D architecture including scaffolds, cell-derived matrices, multicellular spheroids and biochips will be described. The ability to simulate the microenvironment of tumours and vital organs including the liver, kidney, heart and intestine which have major impact on drug absorption, distribution, metabolism and toxicity will be evaluated. Examples of the application of 3D models including a role in formulation development, pharmacokinetic profiling and toxicity testing will be critically assessed. Although utilisation of 3D cell culture models in the field of drug delivery is still in its infancy, the area is attracting high levels of interest and is likely to become a significant in vitro tool to assist in drug product development thus reducing the requirement for unnecessary animal studies. Keywords: 3D cell culture; In vitro biopharmaceutical tool; Drug delivery; Biomaterials; The 3 Rs”

PolySciTech PLGA used for development of nanofiber diameter measurement tool

PolySciTech (www.polyscitech.com) provides a wide array of biodegradable polymers including poly(lactide-co-glycolide).  Recently PolySciTech PLGA (AP082) was dissolved 25% w/v in hexafluoroisopropanol and electrospun through a 25Ga needle to form reference fibers used in the development of a nanofiber measurement tool. Read more: Hotaling, Nathan A., Kapil Bharti, Haydn Kriel, and Carl G. Simon. “DiameterJ: A Validated Open Source Nanofiber Diameter Measurement Tool.” Biomaterials (2015). http://www.sciencedirect.com/science/article/pii/S0142961215004652

“Abstract: Despite the growing use of nanofiber scaffolds for tissue engineering applications, there is not a validated, readily available, free solution for rapid, automated analysis of nanofiber diameter from scanning electron microscope (SEM) micrographs. Thus, the goal of this study was to create a user friendly ImageJ/FIJI plugin that would analyze SEM micrographs of nanofibers to determine nanofiber diameter on a desktop computer within 60 seconds. Additional design goals included 1) compatibility with a variety of existing segmentation algorithms, and 2) an open source code to enable further improvement of the plugin. Using existing algorithms for centerline determination, Euclidean distance transforms and a novel pixel transformation technique, a plugin called “DiameterJ” was created for ImageJ/FIJI. The plugin was validated using 1) digital synthetic images of white lines on a black background and 2) SEM images of nominally monodispersed steel wires of known diameters. DiameterJ analyzed SEM micrographs in 20 seconds, produced diameters not statistically different from known values, was over 10-times closer to known diameter values than other open source software, provided hundreds of times the sampling of manual measurement, and was hundreds of times faster than manual assessment of nanofiber diameter. DiameterJ enables users to rapidly and thoroughly determine the structural features of nanofiber scaffolds and could potentially allow new insights to be formed into fiber diameter distribution and cell response. Keywords: ImageJ; image analysis; FIJI; scaffold; morphology; structure”

PEG-PLA used to create porous film to encourage cellular growth

PolySciTech (www.polyscitech.com) provides a wide array of PEG-PLA block copolymers. Recently these types of polymers were utilized in order to generate honey-comb shaped films using a templating technique. It was found that these surfaces could support the growth of GFP-U87 cells indicating that these polymers can be a suitable matrix for cell growth. Read more: Yao, Bingjian, Qingzeng Zhu, Linli Yao, and Jingcheng Hao. “Fabrication of honeycomb-structured poly (ethylene glycol)-block-poly (lactic acid) porous films and biomedical applications for cell growth.” Applied Surface Science (2015). http://www.sciencedirect.com/science/article/pii/S0169433215002093

“Abstract: A series of poly(ethylene glycol)-block-poly(lactic acid) (PEG-PLA) copolymers with a hydrophobic PLA block of different molecular weights and a fixed length hydrophilic PEG were synthesized successfully and charaterized. These amphiphilic block copolymers were used to fabricate honeycomb-structured porous films using the breath figure (BF) templating technique. The surface topology and composition of the highly ordered pattern film were further characterized by scanning electron microscopy (SEM), atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS) and fluorescence microscopy. The results indicated that the PEG-to-PLA block molecular weight ratio influenced the BF film surface topology. The film with the best ordered pores was obtained with a PEG-to-PLA ratio of 2.0 × 103: 3.0 × 104. The self-organization of the hydrophilic PEG chains within the pores was confirmed by XPS and fluorescence labeled PEG. A model is proposed to elucidate the stabilization process of the amphiphilic PEG-PLA aggregated architecture on the water droplet-based templates. In addition, GFP-U87 cell viability has been investigated by MTS test and the cell morphology on the honeycomb-structured PEG-PLA porous film has been evaluated using phase-contrast microscope. This porous film is shown to be suitable as a matrix for cell growth. Highlights: Honeycomb-structured PEG-PLA porous films were fabricated. The organization of pores depends on molecular weight ratio of PEG-to-PLA block. The pores in the film were internally decorated with a layer of PEG. The honeycomb-structured PEG-PLA film was suitable as a substrate for cell growth. Keywords: Poly(ethylene glycol)-block-poly(lactic acid) (PEG-PLA); Breath figure; Honeycomb-structured film; Migration; Cell growth”

Bingjian, 2015 honeycomb cell PEG-PLA

PolySciTech PLGA used for microsphere delivery of mesenchymal stem cells in treatment of heart attack

PolySciTech (www.polyscitech.com) provides a wide array of PLGA products. Recently PLGA purchased from PolySciTech was utilized to develop PLGA-PEG microparticles which were subsequently loaded with stem cells and investigated for use in treatment of tissue damage resultant from animal model induced heart attack. Read more: Lee, Young Sook, Kwang Suk Lim, Jung-Eun Oh, Arum Yun, Wan Seok Joo, Hyun Soo Kim, Chae-Ok Yun, and Sung Wan Kim. “Development of porous PLGA/PEI< sub> 1.8 k</sub> biodegradable microspheres for the delivery of mesenchymal stem cells (MSCs).” Journal of Controlled Release (2015). http://www.sciencedirect.com/science/article/pii/S016836591500005X

“Abstract: Multipotent mesenchymal stem cells (MSCs) promise a therapeutic alternative for many debilitating and incurable diseases. However, one of the major limitations for the therapeutic application of human MSC (hMSC) is the lengthy ex vivo expansion time for preparing a sufficient amount of cells due to the low engraftment rate after transplantation. To solve this conundrum, a porous biodegradable polymeric microsphere was investigated as a potential scaffold for the delivery of MSCs. The modified water/oil/water (W1/O/W2) double emulsion solvent evaporation method was used for the construction of porous microspheres. PEI1.8k was blended with poly(lactic-co-glycolic acid) (PLGA) to enhance electrostatic cellular attachment to the microspheres. The porous PLGA/PEI1.8k (PPP) particles demonstrated an average particle size of 290 μm and an average pore size of 14.3 μm, providing a micro-carrier for the MSC delivery. PPP particles allowed for better attachment of rMSCs than non-porous PLGA/PEI1.8k (NPP) particles and non-porous (NP) and porous PLGA (PP) microspheres. rMSC successfully grew on the PPP particles for 2 weeks in vitro. Next, PPP particles loaded with 3 different amounts of hMSC showed increased in vivo engraftment rates and maintained the stemness characteristics of hMSC compared with hMSCs-alone group in rats 2 weeks after intramyocardial administration. These customized PPP particles for MSC delivery are a biodegradable and injectable scaffold that can be used for clinical applications. Keywords: PLGA; Porous microparticle; Mesenchymal stem cell; Human stem cell; Cell therapy; PEI1.8k”

polyscitech PLGA heart attack treatement