PLGA in Tissue Engineering
The inability to deliver bioactive agents locally in a transient but sustained manner is one of the challenges on the development of bio-functionalized scaffolds for tissue engineering (TE) and regenerative medicine. The mode of release is especially relevant when the bioactive agent is a growth factor (GF), because the dose and the spatiotemporal release of such agents at the site of injury are crucial to achieve a successful outcome. Strategies that combine scaffolds and drug delivery systems have the potential to provide more effective tissue regeneration relative to current therapies. Nanoparticles (NPs) can protect the bioactive agents, control its profile, decrease the occurrence and severity of side effects and deliver the bioactive agent to the target cells maximizing its effect.
Tissue Engineering strategies based on the combination of bioactive agent-loaded NPs and scaffolds has remarkably grown in recent years, leading to significant advances in the field of Tissue Engineering and Regenerative Medicine. Controlled release of bioactive agents from biodegradable scaffolds can enhance the ef- ficacy of TE approaches.
To date, poly-lactic-co-glycolic-acid (PLGA) is the most well known and widely appliedpolymer in controlled release systems. This synthetic polymer has found great success as a base material for biomedical applications due to its: (i) biocompatibility; (ii) tailored biodegradation rate (depending on the molecular weight and copolymer ratio); (iii) approval for clinical use in humans by the U.S. Food and Drug Administration (FDA); (iv) potential to modify surface properties to provide better interaction with biological materials.PLGA has been used to release a wide range of small molecule drugs, peptides, and proteins, including fertility regulating hormones, growth hormones, steroid hormones,anti-inflammatory drugs, cytokines, chemotherapeutics, antibiotics, narcotic antagonists,insulin, and vaccines [1-10].
Tissue engineering scaffold systems have takenadvantage of embedding loaded PLGA micro& nano particles to enhance release rates of importantactive agents such as growth factors from the scaffolds to the cells[11-17].
Scaffolds containing NPs loaded with bioactive agents can be used for their local delivery, enabling site-specific pharmacological effects such as the induction of cell proliferation and differentiation, and, consequently, neo-tissue formation.
- Tang, L., et al., Immunosuppressive Activity of Size-Controlled PEG-PLGA Nanoparticles Containing Encapsulated Cyclosporine A. J Transplant, 2012. 2012: p. 896141.
- Haddadi, A., et al., Delivery of rapamycin by PLGA nanoparticles enhances its suppressive activity on dendritic cells. J Biomed Mater Res A, 2008. 84(4): p. 885-98.
- Hiremath, J., et al., Entrapment of H1N1 Influenza Virus Derived Conserved Peptides in PLGA Nanoparticles Enhances T Cell Response and Vaccine Efficacy in Pigs. PLoS One, 2016. 11(4): p. e0151922.
- Acharya, S. and S.K. Sahoo, PLGA nanoparticles containing various anticancer agents and tumour delivery by EPR effect. Adv Drug Deliv Rev, 2011. 63(3): p. 170-83.
- Garinot, M., et al., PEGylated PLGA-based nanoparticles targeting M cells for oral vaccination. J Control Release, 2007. 120(3): p. 195-204.
- Santos, D.M., et al., Towards development of novel immunization strategies against leishmaniasis using PLGA nanoparticles loaded with kinetoplastid membrane protein-11. Int J Nanomedicine, 2012. 7: p. 2115-27.
- Tong, G.F., N. Qin, and L.W. Sun, Development and evaluation of Desvenlafaxine loaded PLGA-chitosan nanoparticles for brain delivery. Saudi Pharm J, 2017. 25(6): p. 844-851.
- Han, M.J., Biodegradable membranes for the controlled release of progesterone. 1. Characterization of membrane morphologies coagulated from PLGA/progesterone/DMF solutions. Journal of applied polymer science, 2000. 75(1): p. 60-67.
- Malathi, S., et al., Novel PLGA-based nanoparticles for the oral delivery of insulin. Int J Nanomedicine, 2015. 10: p. 2207-18.
- Aggarwal, S., S. Yadav, and S. Gupta, EGFR targeted PLGA nanoparticles using gemcitabine for treatment of pancreatic cancer. J Biomed Nanotechnol, 2011. 7(1): p. 137-8.
- Yuan, Y., et al., Modification of porous PLGA microspheres by poly-l-lysine for use as tissue engineering scaffolds. Colloids Surf B Biointerfaces, 2017. 161: p. 162-168.
- Fahimipour, F., et al., 3D printed TCP-based scaffold incorporating VEGF-loaded PLGA microspheres for craniofacial tissue engineering. Dent Mater, 2017. 33(11): p. 1205-1216.
- Zhang, H.X., et al., Biocompatibility and osteogenesis of calcium phosphate composite scaffolds containing simvastatin-loaded PLGA microspheres for bone tissue engineering. J Biomed Mater Res A, 2015. 103(10): p. 3250-8.
- Wenk, E., et al., Microporous silk fibroin scaffolds embedding PLGA microparticles for controlled growth factor delivery in tissue engineering. Biomaterials, 2009. 30(13): p. 2571-81.
- Ortega-Oller, I., et al., Bone Regeneration from PLGA Micro-Nanoparticles. Biomed Res Int, 2015. 2015: p. 415289.
- Nandagiri, V.K., et al., Incorporation of PLGA nanoparticles into porous chitosan-gelatin scaffolds: influence on the physical properties and cell behavior. J Mech Behav Biomed Mater, 2011. 4(7): p. 1318-27.
- Habraken, W.J., et al., PLGA microsphere/calcium phosphate cement composites for tissue engineering: in vitro release and degradation characteristics. J Biomater Sci Polym Ed, 2008. 19(9): p. 1171-88.