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.

Hybrid Bioprinting of Chondrogenically Induced Human Mesenchymal Stem Cell Spheroids

“…Nowadays, articular cartilage defects are already being treated with cell-based regenerative therapies, such as autologous chondrocyte implantation (ACI). This two-step surgical procedure includes the isolation of autologous articular chondrocytes from a non-weight bearing region, the in vitro expansion and the reinjection into the defect site (Davies and Kuiper, 2019). Another commonly used approach is Matrixassisted ACI (MACI) which is an ex vivo engineered hybrid construct, where isolated autologous chondrocytes are seeded onto a biomaterial, a bovine-derived type I/III collagen scaffold, before implantation in the defect (Foldager et al, 2012;Basad et al, 2015).…”

Optimization of immunohistochemical detection of collagen type II in osteochondral sections by comparing decalcification and antigen retrieval agent combinations

“…As masking of epitope due to tissue processing hinders antibody binding, it is important to use the correct combination of decalcifying agent and antigen retrieval method. Collagen type II is the major constituent of extracellular matrix seen in articular cartilage and therefore is an optimal assessment parameter during immunocyto‐histochemical analysis (Roberts et al, ; Davies and Kuiper, ). We analyzed five different approaches to antigen retrieval using heat, enzymes and a combination of enzymes to finally assess collagen II staining.…”

Pathomechanisms of Posttraumatic Osteoarthritis: Chondrocyte Behavior and Fate in a Precarious Environment

“…Due to the still limited lifespan of the prosthetic devices and an increased risk for a revision surgery in younger patients [167], arthroplasty is often not appropriate for PTOA patients, which have an approximately 10-year earlier need for joint replacement as compared to other OA patients [80], emphasizing the urgent need for novel treatment strategies. Despite of the growing trend in regenerative medicine, including cell-based approaches, such as autologous-chondrocyte implantation (ACI) [168], injections of MSC or MCS-derived exosomes [169,170], as well as tissue engineering, combining cells, biomimetic matrices and bioactive components [171][172][173][174], this review will primarily focus on current pharmacological approaches allowing modulation of chondrocyte's behavior and fate.…”