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

Abstract

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.

Recent Advances in Bioplastics: Application and Biodegradation

“…George Guo-Qiang Chen's group observed that 3-hydroxybutyrate (3HB) monomers leaking after hydrolysis of implanted PHB promoted calcium deposition and alkaline phosphatase in murine osteoblasts [198]. Wei and colleagues used PHA as porous microparticles as an injectable scaffold for hMSC delivery [199]. These hMSC differentiated in vivo in a mouse model and gave rise to ectopic bone formation.…”

An In Situ Reversible Heterodimeric Nanoswitch Controlled by Metal‐Ion–Ligand Coordination Regulates the Mechanosensing and Differentiation of Stem Cells

“…Small‐molecule‐based in situ reversible heterodimeric nanoswitching offers cytocompatible and minimally invasive control to regulate reversible cell adhesion and release on implanted materials. We subcutaneously implanted (BP‐AuNP)‐grafted substrate into mice and injected hMSCs onto substrate ( Figure A).…”

Advanced Bottom‐Up Engineering of Living Architectures

“…Red channel: dead; green channel: live cells. Reproduced with permission . Copyright 2018, Wiley‐VCH.…”

“…Adding to these technologies, open porous microparticle platforms have also received a significant focus for 3D microtissues assembly owing to their improved gases/nutrients and waste metabolites exchange with the surrounding microenvironment. Recently microporous particles technology was advanced with the fabrication of highly open porous polyhydroxyalkanoate (PHA) microspheres (OPMs; 300–360 µm in diameter, Figure B), which are able to harbor stem cells in their interconnected network while also assuring a higher cell viability and continuous proliferation in comparison to their less porous counterparts …”