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.

keywords

ARTICULAR-CARTILAGE; HYALURONIC-ACID; INTRAARTICULAR INJECTION; CHEMISTRY; HYDROGEL; KNEE; OSTEOARTHRITIS; REGENERATION; IMPLANTATION; TECHNOLOGIES

subject category

Engineering; Science & Technology - Other Topics; Materials Science

authors

Sousa, MP; Passos, CT; Fürsatz, M; Lee, H; Patrício, SG; Mano, JF; Nürnberger, S

Groups

G5 - Biomimetic, Biological and Living Materials

Projects

Desenvolvimento de uma membrana periodontal multicamada composta por blocos inovativos a base de polimeros de origem marinha e enzima para regeneracao guiada de osso que possui mineralizacao enzimatica controlada. (MIMETIc)

Metodologias eficientes para a conjugação de polissacarídeos naturais com péptidos para obtenção de membranas multifuncionais para regeneração periodontal. (COP2P)

Dispositivos Supramoleculares Auto-Regulados baseados na Complementaridade dos Pares de Base do ADN: Uma Tecnologia Biomimética e com Reconheciemnto Molecular para Isolar Células Específicas para Aplicações Biomédicas (SUPRASORT)

Collaboratory for Emerging Technologies, CoLab (EMERGING TECHNOLOGIES)

CICECO - Aveiro Institute of Materials (UIDB/50011/2020)

CICECO - Aveiro Institute of Materials (UIDP/50011/2020)

acknowledgements

This work was financed by national funds (OE) through FCT, Fundacao para a Ciencia e a Tecnologia, I.P., in the scope of the following projects: MIMETIc'' (PTDC/BTM-MAT/31210/2017) and "COP2P" (PTDC/QUI-QOR/30771/2017), both also supported by the Operational Programme Competitiveness and Internationalization (POCI-01-0145-FEDER-031210 and POCI-01-0145-FEDER-030771), in its FEDER component, and "SUPRASORT" (PTDC/QUI-OUT/30658/2017), also supported by CENTRO 2020, Center Portugal Regional Operational Programme (CENTRO-01-0145-FEDER-030658) in the component FEDER. This work was also developed within the scope of the project CICECO - Aveiro Institute of Materials (UIDB/50011/2020, UIDP/50011/2020 & LA/P/006/2020), financed by national funds through the FCT/MEC (PIDDAC). M.P.S and S.G.P. gratefully acknowledge FCT for the Ph.D. grant (SFRH/BD/97606/2013) and for the individual contract (2020.00366.CEECIND), respectively. The authors acknowledge Evercyte (Evercyte, Vienna, Austria, Cat# CHS-001-005) by kindly providing ASC/TERT1 cells.