Injectable Hyaluronic Acid Hydrogel Containing Platelet Derivatives for Synovial Fluid Viscosupplementation and Growth Factors Delivery

Abstract

Osteoarthritisis a highly prevalent musculoskeletal disorder characterized by degradation of cartilage and synovial fluid (SF). Platelet derivatives as platelet‐rich plasma (PRP) and platelet lysate have great potential in the treatment of osteoarthritis because they contain biologically active substances including growth factors (GFs). Rapid release of GFs and their short biological half‐life are factors that can limit the therapeutic impact of PRP therapy. Herein, the first work that describes hydrogels based on polyaldehyde derivative of hyaluronic acid (HA‐OX) as carriers of platelet derivatives for in situ applications is presented, which can be a possible solution to the problem. HA‐OX hydrogels containing 50% (w/w) of PRP or platelet lysate can be injected using a syringe due to low viscosity(<10 Pa s) and injection force (<20 N), and reach elastic modulus up to 2000 Pa. Insulin‐like GF‐1 and Platelet‐derived GF‐AB release from HA‐OX hydrogels (mesh size 297–406 nm) by Fickian and non‐Fickian diffusion respectively. The released PRP GFs maintain their ability to induce cell proliferation (87%–92%). Based on the obtained results, the unique concept of a new material that can restore viscoelastic properties of SF and at the same time gradually deliver GFs from platelet derivatives is designed.

Hydrogels for ameliorating osteoarthritis: Mechanical modulation, anti‐inflammation, and regeneration

“…Drugs-laden hydrogel Dex-laden OP-PEG-HY hydrogel [64] Dynamic hydrazone linkages � pH-sensitive � Suitable viscoelastic properties � Self-healing � Sustained release (28 days) � Radical and inflammation inhabitation � Osteogenic activities � Poor degradability � Limited protein adsorption CLX@Lipo@HA hydrogel [27] Non-covalent interaction Schiff base linkages HA/PRP/BM hydrogel [65] Schiff base linkages � Self-healing � pH-responsive release � ROS elimination � Chondrocyte proliferation promotion � Poor mechanical properties � Fast degradation � Limited cell attachment G3@nCe/GelMA hydrogel [66] Electrostatic interactions � Enhanced mechanical properties � Biodegradation � ROS elimination � MSCs proliferation and adhesion � Osteogenic activity � Introduction of photoinitiators � Cytotoxicity PRP-loaded hydrogel HA-OX hydrogel contains PRP [67] Covalent crosslinking by POA (ii-iv) The relative expression of pro-inflammatory markers (IL-6, IL-1β) and anti-inflammatory (TGF-β) genes on MC3T3-E1 cells at 7, 14, and 21 days after treatment. OM (positive control), GM (untreated cells).…”

“…[27] Copyright 2022, KeAi Communications Co. (c) Representative image of 3T3 cells cultured for 72 h with samples of media from HA-OX hydrogels (after 3 h) containing 50% (w/w) of NS (i), 50% (w/w) of PRP (ii); RLU of media sampling from different 3T3 cells cultivation system at 72 h. Reproduced with permission. [67] Copyright 2023, Wiley. [112] Copyright 2022, Wiley.…”

“…Meanwhile, Velebny et al. proposed an injectable HA hydrogel containing PRP for synovial fluid viscosupplementation and GF delivery [67] . To avoid rapid clearance and short half‐life of cytokines, the strategy that incorporating PRP into hydrogels was practiced to prolong the retention time of PRP and improve the efficiency of treatment.…”

“…(b) Cumulative release of IGF‐1 (i) and PDGF‐AB (ii) from HA‐OX hydrogels containing PRP with different mesh sizes (ξ). (c) Representative image of 3T3 cells cultured for 72 h with samples of media from HA‐OX hydrogels (after 3 h) containing 50% (w/w) of NS (i), 50% (w/w) of PRP (ii); RLU of media sampling from different 3T3 cells cultivation system at 72 h. Reproduced with permission [67] . Copyright 2023, Wiley.…”