Patterned Mussel-Inspired Freestanding Membranes as Efficient Delivery Device of Therapeutic Stem Cells for Cartilage Repair

Abstract

Articular cartilage injuries are currently one of the world's top health concerns owing to its limited capacity of self-renewal, thus raising to the economic burden in the healthcare system. Cell implantation strategies resorting to a suitable delivery platform hold a great promising approach to increase cell retention to be further supplied in a sufficient amount to the cartilage defects. So far, macromolecular engineering toolboxes for designing cell-carrier devices with on-demand cell delivery efficiency are rarely reported. Herein, anisotropically patterned mussel-inspired membranes, comprising oppositely charged marine-origin biopolymers (e.g., chitosan and alginate) combined in a multilayered fashion with catechol-functionalized hyaluronic acid (DOPA-HA), through electrostatically driven layer-by-layer (LbL) assembly approach, are developed. The seamless combination of nanotopography and catechol molecular cues in one single platform significantly augments ASC/TERT1 adhesion at the patterned DOPA-HA membrane surface. These highest cell density membranes are further applied onto human chondral discs ex vivo models to evaluate their capability to act as cell delivery vehicles. Results show the successful cell migration and retention at cartilage surface, wherein they spread to inhabit both superficial empty lacunae and furrows. Therefore, the present study supplies an important strategy for designing cell delivery vehicles to be applied on cell-based therapies.