Development of a hoffa’s fat pad on chip
Carolina Serrano Larrea (TNW-DBE), Thanh Le (TNW-DBE) , Bram Zoetebier (TNW-DBE), Marcel Karperien (TNW-DBE)
Abstract
The Hoffa’s fat pad (HFP) within the knee joint is a pivotal yet often overlooked component crucial for joint stability and cushioning against mechanical forces. However, replicating its complex dynamics in controlled in vitro environments presents significant challenges. This study addresses this gap by introducing a novel Fat Pad-on-Chip (FPoC) platform, leveraging Organ-on-Chip (OoC) technology to emulate the dynamic characteristics of the HFP faithfully.
The study focuses on developing on-chip adipose tissue constructs using a tunable hybrid hydrogel matrix composed of Hyaluronic Acid (HA), Dextran (Dex), and Gelatin (Gel), in conjunction with an immortalized mesenchymal stem cell line (hMSC-hTERT).
Hydrogels with varying stiffness were synthesized to mimic the mechanical properties of the native HFP across different physiological conditions, with particular attention to achieving storage moduli analogous to those of adipose tissue. Subsequent encapsulation of hMSC-hTERT cells within these hydrogel formulations demonstrated high cell viability, proliferation, and adipogenic differentiation potential. Moreover, the FPoC design incorporates microscale mechanical actuators to simulate the dynamic environment of the fat pad, enhancing the physiological fidelity of the FPoC, and offering a promising avenue for studying adipose tissue behavior during joint movement compared to conventional static in vitro models. Furthermore, validation experiments are currently underway, including evaluating cell compression, adipocyte differentiation, and lipid metabolism within the microfluidic chip under static and actuated conditions.
Overall, this technology holds considerable promise for advancing our comprehension of the role of the fat pad in degenerative joint disorders, potentially leading to novel therapeutic interventions and improved patient outcomes.