Biomedical polymeric materials are a type of polymeric materials used in artificial organs, tissue engineering and regenerative medicine, in vivo and in vitro diagnostics, pharmaceutical preparations and medical devices. Among them, degradable medical polymer materials can be gradually degraded by specific or non-specific cleavage of molecular chains in the internal environment, and the degradation products can be absorbed by the human body or excreted through metabolic processes. Therefore, this type of material can be automatically eliminated after fulfilling its mission in the body and will not cause any secondary damage to human health. In recent years, it has become a type of biomedical material that has attracted much attention. Aliphatic polyester is a typical type of biodegradable polymer material. Among them, polylactic acid (PLA) is currently one of the most mature industrialized materials with the largest output and the most widely used materials. It has good biocompatibility and biodegradability properties. biodegradability, etc. However, PLA has weak nucleation ability and low crystallization rate under homogeneous conditions. Conventional processing methods can only produce products with low crystallinity or even an amorphous state, resulting in greatly reduced mechanical properties and heat resistance. At the same time, PLA has poor hydrophilicity and degradation. These limitations limit the application of PLA to some extent. Polyglycolic acid (PGA) is currently one of the fastest degrading aliphatic polyester materials and the degradation conditions are mild. It can be degraded to carbon dioxide and water in the natural environment. At the same time, due to its regular structure, its crystallization performance is better than that of PLA, and it has good mechanical properties and gas barrier properties, but it also has shortcomings such as difficulty in processing and insufficient toughness. By copolymerizing lactic acid (LA) and glycolic acid (GA), the advantages of PLA and PGA can be fully exploited and their respective shortcomings compensated for. The resulting PLGA has good degradability, biocompatibility, excellent mechanical properties and heat resistance. Its properties and controlled degradation make it one of the first batches of degradable medical polymer materials to be certified by the US Food and Drug Administration (FDA). It is widely used in areas such as controlled drug release, medical fibre materials and bone tissue engineering scaffolds. PLGA is usually a white solid with a phase transition temperature between 40 and 60°C and is in a glassy state at room temperature. Its molecular chain exhibits strong rigidity and is generally an amorphous or semi-crystalline polymer. Studies have shown that the polymerization method, comonomer ratio and relative molecular mass differences in the synthesis of PLGA will give PLGA different aggregation structures, thereby affecting its hydrophilicity, mechanical strength and biodegradation rate.
Figure 1. SEM imaging of PLGA/Ge scaffolds. (Vázquez N, et al.; 2019)
Degradation properties of PLGA
The degradation of PLGA is mainly hydrolytic degradation, and the process is divided into four stages: (1) Hydration: Water molecules penetrate into the amorphous region and destroy the van der Waals force and hydrogen bonds, resulting in a decrease in the glass transition temperature; (2) Initial degradation: The ester bonds of the polymer main chain break due to hydrolysis, resulting in a decrease in molecular weight and mechanical properties. During this process, the amorphous region degrades first and then extends to the crystalline region; (3) Continuous degradation: The polymer becomes oligomer fragments and the overall mass begins to decrease; (4) Solubilization: The oligomers are further hydrolyzed and become smaller fragments or monomers dissolved in the medium. In general, the degradation properties of PLGA mainly depend on the comonomer ratio, crystallinity, relative molecular weight, pH value, heat treatment conditions, and mechanical load.
Application of PLGA
Among many biodegradable polymer materials, linear aliphatic polyesters are the most widely studied and applied. As biomedical polymer materials, these polymers will eventually degrade and metabolize into carbon dioxide and water in the human body, and will not cause harm to the human body. Therefore, they are widely used in biomedical fields such as drug-controlled release, medical surgical sutures, and bone tissue engineering.
PLGA is widely used as a material for drug delivery systems. By encapsulating drugs in PLGA microspheres, nanoparticles or films, the drug can be slowly released, the stability and bioavailability of the drug can be increased, and the drug release rate can be controlled, thereby improving the therapeutic effect. The mechanism of PLGA drug release control is achieved through the degradation of PLGA. When PLGA is exposed in the body, the penetration of water molecules will cause the degradation of PLGA and form a microporous structure, thereby releasing the drug from the micropores. Studies have found that the rate of controlled release of PLGA drugs is regulated by a variety of factors, such as the chemical structure, relative molecular weight, composition ratio, material shape and preparation method of PLGA. By adjusting these factors, drug delivery for a longer time can be achieved. In addition, by modifying the PLGA structure, the formulation properties of PLGA, such as drug stability, degradability, release characteristics and drug targeting, can be improved. The hydrophilicity of PLGA can be improved by introducing polyethylene glycol (PEG) and polyethylene oxide (PEO). By grafting polyvinyl alcohol (PVA), the degradation mechanism of PLGA can be transformed from bulk erosion to surface erosion, thereby improving the degradation performance of PLGA, and grafting positively charged groups (such as amino groups) to enhance cell adhesion and drug absorption.
Sutures are a special type of thread used to suture wounds during surgery, but traditional sutures often need to be removed after the wound tissue heals, causing secondary damage to the tissue. In the 1970s, absorbable sutures based on PGA were developed, followed by the invention of PLGA sutures, which showed good tensile strength and excellent biocompatibility in wound healing and are gradually replacing traditional gut sutures. In recent years, with the continuous deepening of research, people are no longer satisfied with the single-function PLGA surgical sutures. Researchers have proposed a biodegradable PLGA surgical suture, which is combined with a drug delivery carrier by physical weaving. It can not only maintain its own mechanical properties, but also achieve local and continuous drug release, relieving pain during wound healing.
- Bone Tissue Engineering Scaffold
Bone tissue engineering scaffold is a structure used to repair and regenerate damaged bone tissue. It can provide support and growth environment for new bone cells, and gradually degrade during bone healing, and eventually be replaced by new bone tissue. Tissue engineering scaffolds should have the characteristics of biodegradability, biocompatibility, bioactivity, structural continuity and stability. PLGA bone tissue engineering scaffolds, including electrospun nanofiber scaffolds, 3D printed scaffolds, microspheres/nanoparticles, gels, multiphase scaffolds, etc., are widely used in the field of bone tissue engineering due to their good biological and engineering properties.
References
- Vázquez N, et al.; Influence of the PLGA/gelatin ratio on the physical, chemical and biological properties of electrospun scaffolds for wound dressings. Biomed Mater. 2019, 14(4):045006.
- He Z, et al.; Degradation behavior and biosafety studies of the mPEG-PLGA-PLL copolymer. Phys Chem Chem Phys. 2016, 18(17):11986-99.
