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Microspheres applied in medical applications experience explosive development in recent years, such as drug release, cell culture, and bone tissue engineering, etc. However, there are still some bottlenecks both in economy and technology lay that cannot be ignored. For instance, microsphere technology has not been used in cell culture widely because of its uneconomical cost; as the core of drug‐loaded microsphere, targeted microsphere technology is still not mature enough. Besides, the common microsphere fabrication methods: microfluidic or emulsion technology is difficult to guarantee high biocompatibility of microsphere due to utilization of photoinitiator, crosslinking agent, surfactant, and other substances. Therefore, gas‐shearing technology has been proposed to solve these above shortcomings successfully. This paper focuses more on heteromorphic microspheres rather than on single microspheres which begins with a minute introduction of microsphere preparation methods: microfluidic, coaxial electrospray, emulsion, and gas‐shearing technology. Then its medical applications: drug release, cell culture, bone tissue engineering, and hemostasis are discussed in detail. The disadvantages of fabrication methods and bottlenecks for medical applications at present are also stated. At the end, perspectives of microsphere development are put forward.

Background Melanin is a skin pigment that gives color to the skin, hair, and eyes. The accumulation or over production of melanin can lead to aesthetic problems as well as serious diseases associated with hyperpigmentation. Skin lightening is described as the procedure of using natural or synthetic products to lighten the skin tone or provide an even skin complexion by reducing the amount of melanin in the skin; therefore, skin lightening products help people to treat their skin problems. Ingredients such as hydroquinone, ascorbic acid, and retinoic acid were used as whitening agents to lighten the skin. However, they have many adverse effects on the skin and body health, such as skin irritation. Aim In this review, firstly, discuss on the directly/indirectly target melanogenesis‐related signal pathways. Secondly, summarize potential natural bioactive ingredients with skin lightening properties from plants, marine organisms, microorganisms. Finally, the remaining problems and future challenges are also discussed. Methods For relevant literature, a literature search was conducted using Google Scholar and Web of Science. Natural bioactive compounds, tyrosinase inhibitors, and other related topics were researched and evaluated. Results Natural products isolated from plant and animal resources are potential active cosmetic candidates for lightening the skin tone and skin whitening and protection against UV irradiation. Natural bioactive ingredients as cosmetic whitening additives have attracted increasingly attention due to their safety and cost effectiveness, with few side effects. Conclusion Although natural active substances have been advocated for use in whitening cosmetics in recent years, there are still many challenges due to the fact that traditional inhibitors are used perennial in cosmetics which cannot be easily changed and the research on natural active substances is still in its infancy. In the future, by improving the extraction technique of natural extracts, it is achieved to give a qualitative and quantitative analysis of the active ingredients of the extracts, to determine the effect of the active components of action, and to find the substances that have the best possible whitening effect in natural organisms.

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