Polyhydroxyalkanoates: the natural biopolyester for future medical innovations.

Polyhydroxyalkanoates (PHAs) are a family of natural microbial biopolyesters with the same basic chemical structure and diverse side chain groups. Based on their excellent biodegradability, biocompatibility, thermoplastic properties and diversity, PHAs are highly promising medical biomaterials and elements of medical devices for applications in tissue engineering and drug delivery. However, due to the high cost of biotechnological production, most PHAs have yet to be applied in the clinic and have only been studied at laboratory scale. This review focuses on the biosynthesis, diversity, physical properties, biodegradability and biosafety of PHAs. We also discuss optimization strategies for improved microbial production of commercial PHAs via novel synthetic biology tools. Moreover, we also systematically summarize various medical devices based on PHAs and related design approaches for medical applications, including tissue repair and drug delivery. The main degradation product of PHAs, 3-hydroxybutyrate (3HB), is recognized as a new functional molecule for cancer therapy and immune regulation. Although PHAs still account for only a small percentage of medical polymers, up-and-coming novel medical PHA devices will enter the clinical translation stage in the next few years.

A Micro-Ark for Cells: Highly Open Porous Polyhydroxyalkanoate Microspheres as Injectable Scaffolds for Tissue Regeneration.

To avoid large open surgery using scaffold transplants, small-sized cell carriers are employed to repair complexly shaped tissue defects. However, most cell carriers show poor cell adherences and viability. Therefore, polyhydroxyalkanoate (PHA), a natural biopolymer, is used to prepare highly open porous microspheres (OPMs) of 300-360 µm in diameter, combining the advantages of microspheres and scaffolds to serve as injectable carriers harboring proliferating stem cells. In addition to the convenient injection to a defected tissue, and in contrast to poor performances of OPMs made of polylactides (PLA OPMs) and traditional less porous hollow microspheres (PHA HMs), PHA OPMs present suitable surface pores of 10-60 µm and interconnected passages with an average size of 8.8 µm, leading to a high in vitro cell adhesion of 93.4%, continuous proliferation for 10 d and improved differentiation of human bone marrow mesenchymal stem cells (hMSCs). PHA OPMs also support stronger osteoblast-regeneration compared with traditional PHA HMs, PLA OPMs, commercial hyaluronic acid hydrogels, and carrier-free hMSCs in an ectopic bone-formation mouse model. PHA OPMs protect cells against stresses during injection, allowing more living cells to proliferate and migrate to damaged tissues. They function like a micro-Noah's Ark to safely transport cells to a defect tissue.