Physical and mechanical properties of PLA, and their functions in widespread applications — A comprehensive review The MIT Faculty has made this article openly available. Please share how this access benefits you. Your story matters. Citation Farah, Shady, et al. “Physical and Mechanical Properties of PLA, and Their Functions in Widespread Applications — A Comprehensive Review.” Advanced Drug Delivery Reviews, vol. 107, Dec. 2016, pp. 367–92. As Published http://dx.doi.org/10.1016/J.ADDR.2016.06.012 Publisher Elsevier BV Version Author's final manuscript Citable link http://hdl.handle.net/1721.1/112940 Terms of Use Creative Commons Attribution-NonCommercial-NoDerivs License Detailed Terms http://creativecommons.org/licenses/by-nc-nd/4.0/ ADR-13025; No of Pages 26 Advanced Drug Delivery Reviews xxx (2016) xxx–xxx Contents lists available at ScienceDirect Advanced Drug Delivery Reviews journal homepage: www.elsevier.com/locate/addr Physical and mechanical properties of PLA, and their functions in widespread applications — A comprehensive review☆ Shady Farah a,b,c, Daniel G. Anderson a,b,c,d,e, Robert Langer a,b,c,d,e,⁎ a David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, MA 02139, USA b Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA c Department of Anesthesiology, Boston Children's Hospital, 300 Longwood Ave, Boston, MA 02115, USA d Institute for Medical Engineering and Science, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA e Harvard-MIT Division of Health Science and Technology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA article info abstract Article history: Poly(lactic acid) (PLA), so far, is the most extensively researched and utilized biodegradable aliphatic polyester in Received 4 June 2016 human history. Due to its merits, PLA is a leading biomaterial for numerous applications in medicine as well as in Received in revised form 16 June 2016 industry replacing conventional petrochemical-based polymers. The main purpose of this review is to elaborate Accepted 17 June 2016 the mechanical and physical properties that affect its stability, processability, degradation, PLA-other polymers Available online xxxx immiscibility, aging and recyclability, and therefore its potential suitability to fulfill specific application requirements. This review also summarizes variations in these properties during PLA processing (i.e. thermal Keywords: Physical and mechanical properties degradation and recyclability), biodegradation, packaging and sterilization, and aging (i.e. weathering and PLA hygrothermal). In addition, we discuss up-to-date strategies for PLA properties improvements including compo- Biodegradable polymers nents and plasticizer blending, nucleation agent addition, and PLA modifications and nanoformulations. Incorpo- Polymer processing rating better understanding of the role of these properties with available improvement strategies is the key for Applications successful utilization of PLA and its copolymers/composites/blends to maximize their fit with worldwide appli- cation needs. © 2016 Elsevier B.V. All rights reserved. Contents 1. Introduction............................................................... 0 2. Propertiesoflacticacid-basedpolymers.................................................. 0 2.1. Physicalproperties........................................................ 0 2.2. Mechanicalproperties....................................................... 0 3. PLApropertyvariationduring....................................................... 0 3.1. Processing,thermaldegradationandrecyclability........................................... 0 3.2. Biodegradation.......................................................... 0 3.3. Packagingandsterilization..................................................... 0 3.4. Aging.............................................................. 0 4. PLApropertiesimprovement....................................................... 0 4.1. Plasticizerandpolymerblending.................................................. 0 4.2. Nucleationagents......................................................... 0 5. PLA'spropertiesfunctionsinapplications.................................................. 0 5.1. Medicalapplication........................................................ 0 5.1.1. Woundmanagementandstentapplications......................................... 0 5.1.2. Drugdeliverysystem-basedPLA.............................................. 0 5.1.3. Orthopedic and fixationdevices.............................................. 0 5.1.4. Tissueengineeringandregenerativemedicine........................................ 0 ☆ This review is part of the Advanced Drug Delivery Reviews theme issue on “PLA biodegradable polymers”. ⁎ Corresponding author at: David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, MA 02139, USA. E-mail address: [email protected] (R. Langer). http://dx.doi.org/10.1016/j.addr.2016.06.012 0169-409X/© 2016 Elsevier B.V. All rights reserved. Please cite this article as: S. Farah, et al., Physical and mechanical properties of PLA, and their functions in widespread applications — A comprehensive review, Adv. Drug Deliv. Rev. (2016), http://dx.doi.org/10.1016/j.addr.2016.06.012 2 S. Farah et al. / Advanced Drug Delivery Reviews xxx (2016) xxx–xxx 5.1.5. Otherapplications..................................................... 0 5.2. Non-medicalapplication...................................................... 0 6. Summaryandoutlook........................................................... 0 References.................................................................. 0 1. Introduction direct polymerization and ring opening polymerization are the most used production techniques. Fig. 2 shows the main methods for PLA Poly(lactic acid) or polylactide (PLA) is the most extensively synthesis. researched and utilized biodegradable and renewable aliphatic polyes- In comparison to other biopolymers, the production of PLA has nu- ter. PLA has a proven potential either to replace conventional merous advantages [3], including: 1) Eco-friendly — apart from being petrochemical-based polymers for industrial applications or as a leading derived from renewable resources (e.g., corn, wheat, or rice), PLA is bio- biomaterial for numerous applications in medicine [1,2]. degradable, recyclable, and compostable [2,13]. Its production also con- Environmental, economic, and safety challenges have provoked pack- sumes carbon dioxide [14]. 2) Biocompatibility — the most attractive aging scientists and producers to partially substitute petrochemical- aspect of PLA, especially with respect to biomedical applications. A bio- based polymers with biodegradable ones [3]. PLA as a leading candidate, compatible material should not produce toxic or carcinogenic effects in is a thermoplastic, high-strength, high-modulus polymer that can be local tissues. Also, the degradation products should not interfere with made from annually renewable resources to yield different components tissue healing. PLA hydrolyzes to its constituent α-hydroxy acid when for use in either the industrial packaging field or the biocompatible/ implanted in living organisms, including the human body. It is then in- bioabsorbable medical device market. It is easily processable on standard corporated into the tricarboxylic acid cycle and excreted. Moreover, PLA plastic equipment to yield molded parts, film, or fibers [4,5]. degradation products are non-toxic (at a lower composition) making it As a bioabsorbable polymer, PLA, is one of the most promising bio- a natural choice for biomedical applications [15]. The FDA has also polymers due to the fact that the monomers may be produced from approved PLA for direct contacting with biological fluids [16].3)- non-toxic renewable feedstock as well as due to being a naturally occur- Processibility — PLA has better thermal processibility compared ring organic acid [6,7]. Lactic acid (2-hydroxypropionic acid, LA), a PLA to other biopolymers such as poly(hydroxyl alkanoate) (PHA), constituent unit, since it is a chiral molecule, exists as two enantiomers, poly(ethylene glycol) (PEG) and poly(γ-caprolactone) (PCL). It can be L-andD-lactic acid (Fig. 1), PLA has stereoisomers, such as poly(L-lactide) processed by injection molding, film extrusion, blow molding, (PLLA), poly(D-lactide) (PDLA), and poly(DL-lactide) (PDLLA) [1].Lactic thermoforming, fiber spinning, and film forming [17].4)Energy acid can be made by fermentation of sugars obtained from renewable re- savings — PLA requires 25–55% less energy to produce than sources as such sugarcane or corn starch [4]. Therefore, PLA is an eco- petroleum-based polymers and estimations show that this can be fur- friendly product with better features for use in the human body ther reduced to less than 10% in the future [15]. Lower energy use (nontoxicity). PLA is the first commodity polymer produced from annu- makes PLA production potentially advantageous with respect to cost ally renewable resources [8]. It is classified as generally recognized as as well. Although, despite the above positive features, PLA has draw- safe (GRAS) by the United State Food and Drug Administration (FDA) backs as well, which limit its use in certain applications, mainly: and is safe for all food packaging applications