In Vitro Tissue Engineering of
Hyaline Articular Cartilage
For decades, hyaline articular cartilage has been a primary target for tissue engineering efforts due to
the lack of functional regeneration within the joint. In addition to focal defects, systematic problems
such as OA can destroy the entire cartilage surface, resulting in loss of function and persistent pain.
This chapter highlights both the seminal tissue engineering studies focused on hyaline cartilage,
as well as the latest approaches that incorporate bioreactors, bioactive molecules, and specialized
Tissue engineering, in its classical sense, involves the manipulation of a complex interplay
among biomaterials, growth factors, and cell populations [286] to achieve functional improvement or
restoration. Articular cartilage has been a high priority for tissue engineers since it does not naturally
regenerate after injury. Furthermore, the annual health care costs associated with musculoskeletal
diseases and injuries are extremely large, and an effective reparative solution would not only reduce
costs but also improve the quality of life for millions [287]. The average age for patients undergoing
arthroscopy that exhibit cartilage defects in the knee is 43, and, combined with the demographical
data on adolescent cartilage injuries as discussed previously, the need to create a repair tissue that can
last several decades is a major goal [288]. The earliest attempts at cartilage regeneration involved
transplanting either minced cartilage tissue or dissociated chondrocytes [289]. Surgical solutions to
cartilage defects typically include surface abrasion, microfracture, and debridement, which all can
reduce symptoms. However, the repair tissue formed in response to these procedures is fibrocartilage,
which has biomechanical properties that are markedly different from normal cartilage [288]. Fibro-
cartilage does not have the biochemical composition or structural organization to provide proper
mechanical function within the joint environment and will degrade over time because of insufficient
load-bearing capacity [290, 291]. Because of this, current research is striving to produce a tissue
that is hyaline-like in its biochemical composition and mechanical properties. The first section in
this chapter will focus on in vitro tissue engineering approaches. Attempts to tissue engineer within
the in vivo environment will be discussed along with germane immunological considerations, as
presented in the last chapter of this book.
Early on, it was thought that the in vivo environment should contain all the conditions
necessary to effect successful regeneration. That is, the in vivo environment contains the proper
growth factors and mechanical stimuli, delivered in a well-sequenced manner through autocrine and
paracrine signaling, to effect proper healing, the major missing component being metabolically active
chondrocytes at the defect site. Initial efforts at delivering mechanical stimuli in vitro attempted

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