Regenerative Medicine: A Review of the Evolution of Autologous Chondrocyte Implantation (ACI) Therapy

Abstract

Articular cartilage is composed of chondrons within a territorial matrix surrounded by a highly organized extracellular matrix comprising collagen II fibrils, proteoglycans, glycosaminoglycans, and non-collagenous proteins. Damaged articular cartilage has a limited potential for healing and untreated defects often progress to osteoarthritis. High hopes have been pinned on regenerative medicine strategies to meet the challenge of preventing progress to late osteoarthritis. One such strategy, autologous chondrocyte implantation (ACI), was first reported in 1994 as a treatment for deep focal articular cartilage defects. ACI has since evolved to become a worldwide well-established surgical technique. For ACI, chondrocytes are harvested from the lesser weight bearing edge of the joint by arthroscopy, their numbers expanded in monolayer culture for at least four weeks, and then re-implanted in the damaged region under a natural or synthetic membrane via an open joint procedure. We consider the evolution of ACI to become an established cell therapy, its current limitations, and on-going strategies to improve its efficacy. The most promising developments involving cells and natural or synthetic biomaterials will be highlighted.

Keywords: articular cartilage; autologous chondrocyte implantation (ACI); cell therapy; chondron; extracellular matrix; regenerative medicine.

Figure 1

The structure of articular cartilage and the underlying subchondral bone. From articular cartilage surface to the bone there are four zones—superficial, middle, deep, and calcified. Within the zones, there are differences in the orientation of the collagen fibers, the arrangement of the chondrocytes, and the distribution of proteoglycans and their associated glycosaminoglycans (GAGs).

Figure 2

A timeline consisting of the significant events allowing the evolution of autologous chondrocyte implantation (ACI) to its current form. MACI—matrix-autologous chondrocyte implantation. Adapted from [23,25,26,27,28].

Figure 3

An overview of first-generation autologous chondrocyte implantation (ACI) in which a biopsy of healthy cartilage was removed arthroscopically. Chondrocytes were expanded in culture. An arthrotomy enabled the surgeon to re-inject the cell suspension under an autologous periosteal patch. Image accredited to Mr. Andrew Biggs, Robert Jones and Agnes Hunt Orthopedic Hospital, Oswestry, Shropshire, UK.

Figure 4

The future direction of cell therapy links together the three fundamental principles of tissue engineering. TGF-β— transforming growth factor-beta, IGF-1— insulin-like growth factor-1, PLLA—poly l-lactic acid.