Natural biopolyester microspheres with diverse structures and surface topologies as micro-devices for biomedical applications

Based on their excellent biocompatibility and adjustable biodegradability, the two natural polyesters polylactic acid (PLA) and polyhydroxyalkanoates (PHAs) have been widely used in medical engineering and regenerative medicine. Different types of natural biopolyester microspheres (NBPMs) composed of PLA, PHAs and their derivatives have been designed and used in diverse micro-devices in the last few decades, offering promise for diverse biomedical applications. In addition to biocompatibility and biodegradability, the structure and surface topology of NBPMs also affects in vitro and in vivo cell behaviors such as proliferation, metabolism and differentiation, which are often neglected. In this review, we summarized the preparation methods and properties of diverse NBPMs, including solid, hollow, open porous, and nanofibrous structures, as well as smooth, golf-ball-like, wrinkled, convex, rough and Janus surface topologies, respectively. Moreover, the advantages and limitations of NBPMs for medical applications are analyzed, including tissue engineering (e.g., regeneration of bone, cartilage, liver, tooth, myocardium, and skin), cell engineering for in vitro 3D cell culture, transportation, and cryopreservation, as well as different drug-release models. Finally, we discuss possible future applications of NBPMs with novel, more complex surface structures in light of current trends in biomedicine.