Articular Repair/Regeneration in Healthy and Inflammatory Conditions: From Advanced In Vitro to In Vivo Models

Abstract

The burden of chronic inflammatory diseases of joints and the spine is increasing with population ageing and unhealthy lifestyles. Articular cartilage and intervertebral discs (IVDs) are avascular and aneural tissues with abundant extracellular matrix, low cell density, and reduced regenerative capacity after damage or degeneration. The most advanced in vitro and ex vivo cell-/tissue-/biomaterial-based models and technologies to improve physiological mimicry are discussed, focusing on the impact of inflammation on articular repair/regeneration. In addition, in vivo models, developed to study cartilage and IVD repair/regeneration are addressed. While animal models continue to provide crucial mechanistic and preclinical data, more advanced and robust in vitro/ex vivo cartilage and IVD models, with appropriate extracellular matrix cues and allowing for cellular crosstalk, have seen an exponential growth in the last decade. Due to the complexity of articular microenvironments, adequate in vitro/ex vivo/in vivo models are essential to study the molecular mechanisms underlying articular diseases and develop new therapies for repair/regeneration.

Cartilage-Inspired Hydrogel with Mechanical Adaptability, Controllable Lubrication, and Inflammation Regulation Abilities

“…Cartilage is a key component of the joint system because of its excellent load-bearing and lubrication properties . However, damaged cartilage arising from accident trauma, long-term mechanical overload and pathological osteoarthritis (OA) does not easily self-heal because cartilage is an avascular/aneural tissue. − Failures in load-bearing and joint lubrication will further lead to cartilage degradation and serve OA in turn. Moreover, the amount of reactive oxygen species (ROS) including hydrogen peroxide (H 2 O 2 ), hydroxyl radical (·OH), superoxide anion (O 2 ·– ), is significantly increased, whose overexpression may lead to serve cartilage damage. , Additionally, nitric oxide (NO) is also noted as a prominent biomarker of OA, and its concentration in inflammatory joint fluid maintains at relatively high level .…”

Cartilage tissue healing and regeneration based on biocompatible materials: a systematic review and bibliometric analysis from 1993 to 2022

“…Cartilage is a fundamental type of connective tissue that furnishes vital support and cushioning for the body ( Teixeira et al, 2020 ; Fu et al, 2021 ). It plays an indispensable role in various structures of the body, most notably in joints such as the knee, hip, elbow, shoulder, and ankle, as well as in the spine ( Moutos et al, 2007 ; Teixeira et al, 2020 ).…”

“…Cartilage is a fundamental type of connective tissue that furnishes vital support and cushioning for the body ( Teixeira et al, 2020 ; Fu et al, 2021 ). It plays an indispensable role in various structures of the body, most notably in joints such as the knee, hip, elbow, shoulder, and ankle, as well as in the spine ( Moutos et al, 2007 ; Teixeira et al, 2020 ). Cartilage tissue healing and regeneration is an area of research focused on restoring normal cartilage structure and function, with the main goal of reducing pain, restoring normal joint function and preventing further damage to joint tissues ( Chen et al, 2022 ).…”

Electrospun fibrous membrane reinforced hydrogels with preferable mechanical and tribological performance as cartilage substitutes

“…Unfortunately, the vascular nature of articular cartilage shows that its selfhealing ability is extremely poor, which seriously affects the load-bearing and lubricating ability of articular cartilage. 2,3 In addition, the gradual destruction of the structure and function of cartilage further leads to the degeneration of cartilage and eventually even to the occurrence of osteoarthritis (OA). Therefore, the repair and regeneration of articular cartilage has become one of the main challenges and research hotspots in the field of medicine.…”