Abstract
The demand for injectable Dermal Filler has undergone significant growth with the rapid development of the beauty industry. Poly(lactic acid) (PLA) as a benefit of excellent biocompatibility and long-term promotion of collagen regeneration has been favored as a commonly used filler. However, the effects of chirality and particle size of PLA on the efficacy of dermal filler have not been studied. In this study, we prepared three kinds of microspheres (MSs) consisting of poly(d-lactic acid) (PDLA MS), poly(l-lactic acid) (PLLA MS), or meso-PLA (PDLLA MS) at 5, 10 and 20 μm to reveal the different biological functions as dermal filler. Following intradermal injection into guinea pig, it was found that PLLA MS induced the slightest inflammation, and the level of pro-inflammatory cytokine IL-1β induced by PLLA MS is only 0.3 or 0.7-fold of that induced by PDLA or PDLLA MS, respectively. More importantly, PLLA MS significantly stimulated the regeneration of collagen, which was 1.4 or 1.1 times higher than those stimulated by PDLA MS or PDLLA MS, respectively. The size of PLA MSs did not affect the levels of inflammation and collagen regeneration. The results confirmed the superiority of PLLA as a dermal filler.
Graphical abstract
The chirality of matrix materials and size always affect the properties of polymer microspheres. In this study, the chiral poly(lactic acid) (PLA) microspheres with different sizes were prepared to reveal the biological functions as Dermal Fillers. The poly(l-lactic acid) Microsphere (PLLA MS) were demonstrated to exhibit the slightest inflammatory reaction and the most significant efficacy of promoting the regeneration of skin tissue collagen, while the size did not affect the functions, indicating PLLA MS are promising dermal fillers for clinical application.
During the last decades, people have tried to delay the aging of the skin and keep it healthy in various ways. The usual methods are deep cleaning, moisturization, and sun protection, etc. Facial rejuvenation is also regulated by exercise and diet. However, in most cases, these methods failed to efficiently repair the skin or eliminate wrinkles . Therefore, in order to achieve the purpose of facial rejuvenation, modern plastic and aesthetic surgery have been applied to restore tissue defects or change the overall appearance . In 19th century, paraffin was used as facial filler for the first time in skin repair, but this undegradable material caused embolism, granuloma, and many other complications and was finally abandoned as skin filler . In 1981, collagen was officially approved by the United States Food and Drug Administration (FDA) as an injectable skin filler in the plastic and aesthetic surgery field . In 2003, the emergence of hyaluronic acid filler brought a turning point for filler industry, and has guided a new direction for the development of biocompatible and permanent filler since then . At present, there are many kinds of fillers on the market, mainly including fat, collagen, hyaluronic acid, calcium hydroxyapatite, etc. The problem is that traditional Injectable Dermal Fillers are rapidly metabolized after injection, and therefore they can only perform a temporary repairing effect and require repeated injection. In the meantime, it may increase the risk of inflammation and other adverse effects because of the poor biocompatibility. It is still a big challenge to develop dermal fillers with better properties.
Poly(lactic acid) (PLA) is a biocompatible material with excellent mechanical strength, easy processability, and good biodegradability. For these reasons, PLA has been widely used in tissue engineering, drug delivery, surgical sutures, and orthopedic repair material. In 2004, poly(l-lactic acid) (PLLA) was approved by the FDA for correction of facial fat atrophy associated with human immuno-deficiency virus (HIV) infection. It was because lactic acid derived from the degradation of PLLA can stimulate collagen formation, which is an important component of skin tissue. It could supplement collagen that gradually loses with age, improve skin quality, and fill the dermatolysis and skin sag. The curative effect of collagen filling can last for two years. Unlike the previous dermal filler, PLLA has been favored in the beauty industry in recent years. PLA is classified into poly(d-lactic acid) (PDLA), PLLA, racemic PLA, and meso-PLA (PDLLA) . The chiral of material has an influential effect on the biological propety. For example, Sarasua et al. explored the effect on cell proliferation by co-culturing the L929 mouse fibroblasts and keratinocytes with PLLA and PDLA scaffold. Interestingly, the results were totally different for different cell lines. L929 mouse fibroblasts proliferated better in PLLA than proliferated in PDLA, but keratinocytes proliferated better in PDLA. Wang et al. prepared three different chiral injectable methoxy poly(ethylene glycol)−polyalanine (mPEG–PA) thermosensitive hydrogels, which were injected under the skin of rats to observe inflammation. Studies showed that dextral polyalanine thermogel can induce a controllable level of inflammatory response. It is generally believed that the biocompatibility of l-lactic acid is better because of the lactic acid in organism is l-lactic acid. In the past, most of the biological applications were based on PLLA, and there were few studies on the application of PDLA and PDLLA in Biomedical Materials.
In order to explore the biological functions of different chiral PLA materials as fillers, we prepared chiral PLA microspheres with different particle sizes by emulsion-solvent evaporation method, and injected them into the back skin of guinea pigs to observe the skin inflammation and collagen regeneration. The results of tissue sections after 30 days showed that PDLA microsphere (PDLA MS) cause high-grade inflammation and worst collagen regeneration. PDLLA microsphere (PDLLA MS) produced low-grade inflammation, and better effect of stimulating collagen regeneration. In contrast, PLLA microsphere (PLLA MS) produced the least inflammatory reaction in the skin, and the best effect of stimulating collagen regeneration. Moreover, it degraded slowly which could maintain the effect of promoting collagen regeneration for a long time. At the same time, the particle size did not affect the function of the microsphere. In conclusion, all experimental results show that PLLA MS performance is the best as a dermal filler.
Edit by Chris
Rimless Industry Co.,Ltd.