Optimizing Delivery of Therapeutic Growth Factors for Bone and Cartilage Regeneration

Abstract

Bone- and cartilage-related diseases, such as osteoporosis and osteoarthritis, affect millions of people worldwide, impairing their quality of life and increasing mortality. Osteoporosis significantly increases the bone fracture risk of the spine, hip, and wrist. For successful fracture treatment and to facilitate proper healing in the most complicated cases, one of the most promising methods is to deliver a therapeutic protein to accelerate bone regeneration. Similarly, in the setting of osteoarthritis, where degraded cartilage does not regenerate, therapeutic proteins hold great promise to promote new cartilage formation. For both osteoporosis and osteoarthritis treatments, targeted delivery of therapeutic growth factors, with the aid of hydrogels, to bone and cartilage is a key to advance the field of regenerative medicine. In this review article, we propose five important aspects of therapeutic growth factor delivery for bone and cartilage regeneration: (1) protection of protein growth factors from physical and enzymatic degradation, (2) targeted growth factor delivery, (3) controlling GF release kinetics, (4) long-term stability of regenerated tissues, and (5) osteoimmunomodulatory effects of therapeutic growth factors and carriers/scaffolds.

Methods to accelerate fracture healing – a narrative review from a clinical perspective

“…Pharmacologic interventions can either be applied systemically or directly to the fracture site (injection or intraoperative application) ( 82 , 83 ). Local drug delivery by injecting a medication into the fracture gap could be an option for conservative treatment or for application when delayed healing occurs following surgery.…”

Harnessing the potential of hydrogels for advanced therapeutic applications: current achievements and future directions

“…Consequently, the development of hydrogel systems capable of maintaining the bioactivity of growth factors and facilitating sustained release offers an optimal delivery mechanism. 565 , 566 Owing to the charged nature of many protein-based growth factors, it enables the exploitation of electrostatic interactions with hydrogels to extend the release duration of growth factors. Notably, heparin-based hydrogels, characterized by their significant anionic charge and diverse sulfation patterns, present a compelling approach for the delivery of various growth factors such as fibroblast growth factors (FGFs), hepatocyte growth factors (HGFs), endothelial growth factors (EGFs), and platelet-derived growth factors (PDGFs).…”