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Biomedical Applications of Polylactide (PLA) and its Copolymers

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A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: closed (30 September 2017) | Viewed by 54989

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Special Issue Editors

Prof. Dr. Gaetano Giammona

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Laboratory of Biocompatible Polymers, Department of “Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche” (STEBICEF), University of Palermo, Via Archirafi, 32, 90123 Palermo, Italy
Interests: synthesis and physicochemical characterization of biocompatible polymers; innovative drug delivery systems; drug and gene delivery; hydrogels; three-dimensional scaffolds; tissue engineering; regenerative medicine; targeted release; lipid-based drug delivery systems; theranostic systems
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Prof. Dr. Emanuela Fabiola Craparo

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Laboratory of Biocompatible Polymers, Department of “Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche” (STEBICEF), University of Palermo, Via Archirafi 32, 90123 Palermo, Italy
Interests: functionalization and purification of biopolymers; controlled drug release; active targeting; micro- and nanoparticles; polymeric micelles; lipid-based nanostructured systems; polycations; gene therapy; imaging
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The special Issue “Biomedical Applications of Polylactide (PLA) and its Copolymers” will be focused on current experimental research on the use of PLA, blended or functionalized with other biopolymers, for potential biomedical applications such as in the production of cell or drug delivery systems, applicable in controlled and/or targeted drug release, and in the fabrication of bioresorbable scaffolds for tissue engineering in regenerative medicine. Currently, PLA is already approved by the Food and Drug Administration (FDA) as a component in a wide range of biomedical and pharmaceutical products. This favorable approval arises from its excellent properties, such as biocompatibility, biodegradability and tunable mechanical and physicochemical properties, whereby it can be appropriately processed and engineered to allow a desired biomedical application.

Prof. Dr. Gaetano Giammona
Dr. Emanuela Fabiola Craparo
Guest Editors

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Keywords

PLA-based copolymers
PLA blends
Innovative drug delivery systems
Cell delivery
Scaffolds
Targeted delivery
Regenerative medicine
Tissue engineering

Published Papers (10 papers)

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Editorial

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2 pages, 145 KiB

Open AccessEditorial

Biomedical Applications of Polylactide (PLA) and Its Copolymers

by Gaetano Giammona and Emanuela Fabiola Craparo

Molecules 2018, 23(4), 980; https://doi.org/10.3390/molecules23040980 - 23 Apr 2018

Cited by 20 | Viewed by 3864

Abstract

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(This article belongs to the Special Issue Biomedical Applications of Polylactide (PLA) and its Copolymers)

Research

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11381 KiB

Open AccessArticle

Evaluation of Poly(Lactic-co-glycolic) Acid Alone or in Combination with Hydroxyapatite on Human-Periosteal Cells Bone Differentiation and in Sinus Lift Treatment

by Gabriele Ceccarelli, Rossella Presta, Saturnino Marco Lupi, Nefele Giarratana, Nora Bloise, Laura Benedetti, Maria Gabriella Cusella De Angelis and Ruggero Rodriguez y Baena

Molecules 2017, 22(12), 2109; https://doi.org/10.3390/molecules22122109 - 02 Dec 2017

Cited by 16 | Viewed by 4446

Abstract

Most recent advances in tissue engineering in the fields of oral surgery and dentistry have aimed to restore hard and soft tissues. Further improvement of these therapies may involve more biological approaches and the use of dental tissue stem cells in combination with inorganic/organic scaffolds. In this study, we analyzed the osteoconductivity of two different inorganic scaffolds based on poly (lactic-co-glycolic) acid alone (PLGA-Fisiograft) or in combination with hydroxyapatite (PLGA/HA-Alos) in comparison with an organic material based on equine collagen (PARASORB Sombrero) both in vitro and in vivo. We developed a simple in vitro model in which periosteum-derived stem cells were grown in contact with chips of these scaffolds to mimic bone mineralization. The viability of cells and material osteoconductivity were evaluated by osteogenic gene expression and histological analyses at different time points. In addition, the capacity of scaffolds to improve bone healing in sinus lift was examined. Our results demonstrated that the osteoconductivity of PLGA/HA-Alos and the efficacy of scaffolds in promoting bone healing in the sinus lift were increased. Thus, new clinical approaches in sinus lift follow-up should be considered to elucidate the clinical potential of these two PLGA-based materials in dentistry. Full article

(This article belongs to the Special Issue Biomedical Applications of Polylactide (PLA) and its Copolymers)

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5322 KiB

Open AccessArticle

Biological Properties of Low-Toxicity PLGA and PLGA/PHB Fibrous Nanocomposite Implants for Osseous Tissue Regeneration. Part I: Evaluation of Potential Biotoxicity

by Izabella Krucińska, Bogusława Żywicka, Agnieszka Komisarczyk, Maria Szymonowicz, Stanisława Kowalska, Ewa Zaczyńska, Marcin Struszczyk, Anna Czarny, Piotr Jadczyk, Barbara Umińska-Wasiluk, Zbigniew Rybak and Marek Kowalczuk

Molecules 2017, 22(12), 2092; https://doi.org/10.3390/molecules22122092 - 29 Nov 2017

Cited by 19 | Viewed by 4291

Abstract

In response to the demand for new implant materials characterized by high biocompatibility and bioresorption, two prototypes of fibrous nanocomposite implants for osseous tissue regeneration made of a newly developed blend of poly(l-lactide-co-glycolide) (PLGA) and syntheticpoly([R,S]-3-hydroxybutyrate), PLGA/PHB, have been developed and fabricated. Afibre-forming copolymer of glycolide and l-lactide (PLGA) was obtained by a unique method of synthesis carried out in blocksusing Zr(AcAc)₄ as an initiator. The prototypes of the implants are composed of three layers of PLGA or PLGA/PHB, nonwoven fabrics with a pore structure designed to provide the best conditions for the cell proliferation. The bioactivity of the proposed implants has been imparted by introducing a hydroxyapatite material and IGF1, a growth factor. The developed prototypes of implants have been subjected to a set of in vitro and in vivobiocompatibility tests: in vitro cytotoxic effect, in vitro genotoxicity and systemic toxicity. Rabbitsshowed no signs of negative reactionafter implantation of the experimental implant prototypes. Full article

(This article belongs to the Special Issue Biomedical Applications of Polylactide (PLA) and its Copolymers)

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9849 KiB

Open AccessArticle

Biological Properties of Low-Toxic PLGA and PLGA/PHB Fibrous Nanocomposite Scaffolds for Osseous Tissue Regeneration. Evaluation of Potential Bioactivity

by Boguslawa Żywicka, Izabella Krucińska, Jerzy Garcarek, Maria Szymonowicz, Agnieszka Komisarczyk and Zbigniew Rybak

Molecules 2017, 22(11), 1852; https://doi.org/10.3390/molecules22111852 - 28 Oct 2017

Cited by 10 | Viewed by 4090

Abstract

Abstracts: The aim of the study was to evaluate the biocompatibility and bioactivity of two new prototype implants for bone tissue regeneration made from biodegradable fibrous materials. The first is a newly developed poly(l-lactide-co-glycolide), (PLGA), and the second is a blend of PLGA with synthetic poly([R,S]-3-hydroxybutyrate) (PLGA/PHB). The implant prototypes comprise PLGA or PLGA/PHB nonwoven fabrics with designed pore structures to create the best conditions for cell proliferation. The bioactivity of the proposed implants was enhanced by introducing a hydroxyapatite material and a biologically active agent, namely, growth factor IGF1, encapsulated in calcium alginate microspheres. To assess the biocompatibility and bioactivity, allergenic tests and an assessment of the local reaction of bone tissue after implantation were performed. Comparative studies of local tissue response after implantation into trochanters for a period of 12 months were performed on New Zealand rabbits. Based on the results of the in vivo evaluation of the allergenic effects and the local tissue reaction 12 months after implantation, it was concluded that the two implant prototypes, PLGA + IGF1 and PLGA/PHB + IGF1, were characterized by high biocompatibility with the soft and bone tissues of the tested animals. Full article

(This article belongs to the Special Issue Biomedical Applications of Polylactide (PLA) and its Copolymers)

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3049 KiB

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Margination of Fluorescent Polylactic Acid–Polyaspartamide based Nanoparticles in Microcapillaries In Vitro: the Effect of Hematocrit and Pressure

by Emanuela Fabiola Craparo, Rosa D’Apolito, Gaetano Giammona, Gennara Cavallaro and Giovanna Tomaiuolo

Molecules 2017, 22(11), 1845; https://doi.org/10.3390/molecules22111845 - 28 Oct 2017

Cited by 4 | Viewed by 4013

Abstract

The last decade has seen the emergence of vascular-targeted drug delivery systems as a promising approach for the treatment of many diseases, such as cardiovascular diseases and cancer. In this field, one of the major challenges is carrier margination propensity (i.e., particle migration from blood flow to vessel walls); indeed, binding of these particles to targeted cells and tissues is only possible if there is direct carrier–wall interaction. Here, a microfluidic system mimicking the hydrodynamic conditions of human microcirculation in vitro is used to investigate the effect of red blood cells (RBCs) on a carrier margination in relation to RBC concentration (hematocrit) and pressure drop. As model drug carriers, fluorescent polymeric nanoparticles (FNPs) were chosen, which were obtained by using as starting material a pegylated polylactic acid–polyaspartamide copolymer. The latter was synthesized by derivatization of α,β-poly(N-2-hydroxyethyl)-d,l-aspartamide (PHEA) with Rhodamine (RhB), polylactic acid (PLA) and then poly(ethyleneglycol) (PEG) chains. It was found that the carrier concentration near the wall increases with increasing pressure drop, independently of RBC concentration, and that the tendency for FNP margination decreases with increasing hematocrit. This work highlights the importance of taking into account RBC–drug carrier interactions and physiological conditions in microcirculation when planning a drug delivery strategy based on systemically administered carriers. Full article

(This article belongs to the Special Issue Biomedical Applications of Polylactide (PLA) and its Copolymers)

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Fabrication of Antimicrobial Peptide-Loaded PLGA/Chitosan Composite Microspheres for Long-Acting Bacterial Resistance

by Yuanyuan Li, Rongwei Na, Xiumei Wang, Huiying Liu, Lingyun Zhao, Xiaodan Sun, Guowu Ma and Fuzhai Cui

Molecules 2017, 22(10), 1637; https://doi.org/10.3390/molecules22101637 - 29 Sep 2017

Cited by 45 | Viewed by 6379

Abstract

An antimicrobial decapeptide, KSL-W (KKVVFWVKFK-CONH₂), which could maintain stable antimicrobial activity in saliva, has therefore been widely used to inhibit biofilm formation on teeth and prevent the growth of oral microorganisms for related infectious diseases treatment. In order to control the release of KSL-W for long-term bacterial resistance, KSL-W-loaded PLGA/chitosan composite microspheres (KSL/PLGA/CS MSs) were prepared by electrospraying and combined crosslinking-emulsion methods. Different formulations of microspheres were characterized as to surface morphology, size distribution, encapsulation efficiency, in vitro drug release, and antimicrobial activity. Antibacterial experiment demonstrated the prolonged antimicrobial and inhibitory effects of KSL/PLGA/CS MSs on oral bacteria. Moreover, the cell proliferation assay proved that the released KSL-W antibacterial dosage had no cytotoxicity to the growth of osteoblast MC3T3-E1. Thus, our study suggested that the KSL-W-loaded PLGA/CS composite microspheres may have potentially therapeutic applications as an effective drug delivery system in the treatment of oral infectious diseases such as periodontitis and periodontitis, and also within bone graft substitutes for alveolar bone augmentation. Full article

(This article belongs to the Special Issue Biomedical Applications of Polylactide (PLA) and its Copolymers)

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3564 KiB

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Preventing Surgical Site Infections Using a Natural, Biodegradable, Antibacterial Coating on Surgical Sutures

by Jochen Reinbold, Ann-Kristin Uhde, Ingrid Müller, Tobias Weindl, Jürgen Geis-Gerstorfer, Christian Schlensak, Hans-Peter Wendel and Stefanie Krajewski

Molecules 2017, 22(9), 1570; https://doi.org/10.3390/molecules22091570 - 19 Sep 2017

Cited by 38 | Viewed by 8474

Abstract

Surgical site infections (SSIs) are one of the most common nosocomial infections, which can result in serious complications after surgical interventions. Foreign materials such as implants or surgical sutures are optimal surfaces for the adherence of bacteria and subsequent colonization and biofilm formation. Due to a significant increase in antibiotic-resistant bacterial strains, naturally occurring agents exhibiting antibacterial properties have great potential in prophylactic therapies. The aim of this study was to develop a coating for surgical sutures consisting of the antibacterial substance totarol, a naturally occurring diterpenoid isolated from Podocarpus totara in combination with poly(lactide-co-glycolide acid) (PLGA) as a biodegradable drug delivery system. Hence, non-absorbable monofilament and multifilament sutures were coated with solutions containing different amounts and ratios of totarol and PLGA, resulting in a smooth, crystalline coating. Using an agar diffusion test (ADT), it became evident that the PLGA/totarol-coated sutures inhibited the growth of Staphylococcus aureus over a period of 15 days. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that the coated sutures were not cytotoxic to murine fibroblasts. Overall, the data indicates that our innovative, biodegradable suture coating has the potential to reduce the risk of SSIs and postoperative biofilm-formation on suture material without adverse effects on tissue. Full article

(This article belongs to the Special Issue Biomedical Applications of Polylactide (PLA) and its Copolymers)

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2192 KiB

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Research on a Nonwoven Fabric Made from Multi-Block Biodegradable Copolymer Based on l-Lactide, Glycolide, and Trimethylene Carbonate with Shape Memory

by Joanna Walczak, Michał Chrzanowski and Izabella Krucińska

Molecules 2017, 22(8), 1325; https://doi.org/10.3390/molecules22081325 - 10 Aug 2017

Cited by 8 | Viewed by 5013

Abstract

The presented paper concerns scientific research on processing a poly(lactide-co-glycolide-co-trimethylene carbonate) copolymer (PLLAGLTMC) with thermally induced shape memory and a transition temperature around human body temperature. The material in the literature called terpolymer was used to produce smart, nonwoven fabric with the melt blowing technique. Bioresorbable and biocompatible terpolymers with shape memory have been investigated for its medical applications, such as cardiovascular stents. There are several research studies on shape memory in polymers, but this phenomenon has not been widely studied in textile products made from shape memory polymers (SMPs). The current research aims to explore the characteristics of the PLLAGLTMC nonwoven fabric in detail and the mechanism of its shape memory behavior. In this study, the nonwoven fabric was subjected to thermo-mechanical, morphological, and shape memory analysis. The thermo-mechanical and structural properties were investigated by means of differential scanning calorimetry, dynamic mechanical analysis, scanning electron microscopic examination, and mercury porosimetry measurements. Eventually, the gathered results confirmed that the nonwoven fabric possessed characteristics that classified it as a smart material with potential applications in medicine. Full article

(This article belongs to the Special Issue Biomedical Applications of Polylactide (PLA) and its Copolymers)

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4068 KiB

Open AccessArticle

Development of Antimicrobial Packaging Film Made from Poly(Lactic Acid) Incorporating Titanium Dioxide and Silver Nanoparticles

by Wenhui Li, Cheng Zhang, Hai Chi, Lin Li, Tianqing Lan, Peng Han, Haiyan Chen and Yuyue Qin

Molecules 2017, 22(7), 1170; https://doi.org/10.3390/molecules22071170 - 13 Jul 2017

Cited by 122 | Viewed by 8963

Abstract

Polylactide (PLA)/nano-TiO₂ and PLA/nano-TiO₂/nano-Ag blends films were prepared by a solvent volatilization method. Compared to pure PLA film, the nano-blend films have low water vapor permeability (WVP) and a poor transparency. With the increase of the NPs in the PLA, the tensile strength (TS) and elastic modulus (EM) decreased, while the elongation at break (ε) increased. SEM analysis indicated a rougher cross-section of the nano-blend films. According to the FTIR analysis, no new chemical bonds were formed in the nano-blend films. By using DSC to examine the crystallization and melting behavior, the result shows that the NPs have no effect on the glass transition (T_g) and melting temperature (T_m), but they caused an increase on the cold crystallization (T_c) and crystallinity (X_c). TGA results show that the addition of nanoparticles significantly improved the thermal stability. The PLA nano-blend films show a good antimicrobial activity against. E. coli and Listeria monocytogenes. Most important, we carried out migration tests, and verified that the release of NPs from the nano-blend films was within the standard limits. Full article

(This article belongs to the Special Issue Biomedical Applications of Polylactide (PLA) and its Copolymers)

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2814 KiB

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Pamidronate-Conjugated Biodegradable Branched Copolyester Carriers: Synthesis and Characterization

by Ewa Oledzka, Dagmara Pachowska, Katarzyna Orłowska, Joanna Kolmas, Agata Drobniewska, Ramona Figat and Marcin Sobczak

Molecules 2017, 22(7), 1063; https://doi.org/10.3390/molecules22071063 - 26 Jun 2017

Cited by 7 | Viewed by 4526

Abstract

The need for development of comprehensive therapeutic systems, (e.g., polymer-apatite composites) as a bone substitute material has previously been highlighted in many scientific reports. The aim of this study was to develop a new multifunctional composite based on hydroxyapatite porous granules doped with selenite ions (SeO₃²⁻) and a biodegradable branched copolymer-bisphosphonate conjugate as a promising bone substitute material for patients with bone tumours or bone metastasis. A series of biodegradable and branched copolymer matrices, adequate for delivery of bisphosphonate in the bone-deficient area were synthesized and physico-chemically and biologically (cyto- and genotoxicity assays) characterized. Branched copolymers were obtained using a hyperbranched bis-MPA polyester-16-hydroxyl initiator and Sn(Oct)₂, a (co)catalyst of the ring-opening polymerization (ROP) of l,l-lactide (LLA) and ε-caprolactone (CL). A new amide bond was formed between the hydroxyl end groups of the synthesized copolymer carriers and an amine group of pamidronate (PAM)—the drug inhibiting bone resorption and osteoclast activity in bone. The dependence of the physico-chemical properties of the copolymer matrices on the kinetic release of PAM from the synthesized branched copolymer conjugate-coated hydroxyapatite granules doped with selenite ions was observed. Moreover, the correlation of these results with the hydrolytic degradation data of the synthesized matrices was evidenced. Therefore, the developed composite porous hydroxyapatite doped with SeO₃²⁻ ions/biodegradable copolymer-PAM conjugate appears most attractive as a bone substitute material for cancer patients. Full article

(This article belongs to the Special Issue Biomedical Applications of Polylactide (PLA) and its Copolymers)

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