Repair of Osteochondral Lesions - Engineered Bone: Tissue Engineering Intelligence Unit - page 168

technique. 18 However, due to the limited availability of donor tissue and the induced morbid-
ity at the donor site, the recommended size limit of the damaged area is only about 2 cm 2 .
Fresh Osteochondral Allograft
The technique, used in cases of unconfined, extensive cartilage defects, consists in trans-
plantation of osteochondral tissue from compatible donors (Fig. 1D). Clinical results indicate
successful treatment of large unipolar osteochondral defects, although an unloading period of
1 year after surgery is required. 19 The procedure strongly depends on the access to osteochon-
dral grafts from a sufficient number of donors, in order to minimise size mismatch between
donor and recipient, and is therefore limited to few specialised centers.
Autologous Chondrocyte Implantation
Autologous chondrocyte implantation (ACI) consists in harvesting healthy articular carti-
lage from a minor weight bearing area of the knee joint. Chondrocytes are enzymatically iso-
lated, expanded in monolayer culture and then reinjected under an autologous periosteal flap,
which covers the cartilage defect (Fig. 1B). The results of a pilot clinical study 20 were judged as
good to excellent in 14/16 patients with isolated femoral condyle lesions (up to 6.5 cm 2 in
size). As a consequence, patients began to request this new technique and several companies
started offering the service of in vitro expansion of autologous chondrocytes. Peterson et al 21
reported the clinical, arthroscopic and histological results obtained for the first 101 patients
that were treated with ACI. Reported outcomes suggest some level of repair and improved
symptoms (good to excellent results for 92% of isolated lesions and for 67% of multiple le-
sions), although the lack of comparative groups and of validated assessment methods is a noted
weakness.
The accumulation of clinical experience is in contrast with the understanding of the prin-
ciples of the repair process. Only recently, biopsy samples from the graft site, harvested up to
30 months after surgery, indicated an initial formation of fibrocartilaginous tissue, which pro-
gressively remodelled and where newly synthesised type II collagen accumulated. 22 However,
biopsies were only taken in the center of the repaired defect, and therefore critical evaluation of
graft integration could not be made.
From a surgical standpoint, the main limitation of ACI is related to the mechanism of graft
fixation. It was shown that the periosteal flap delaminates regardless of the postoperative reha-
bilitation protocol, and therefore the control over the fate of the injected cells is poor. 23 This
problem becomes even more relevant when large osteochondral defects are to be treated. In
order to improve ACI, some industrial groups have introduced cell delivery systems based on
membranes (e.g., Verigen) or three-dimensional scaffolds (e.g., Fidia Advanced Biopolymer).
The surgical procedure results easier and provides a higher level of control over graft fixation;
however, the clinical outcome of such procedures has yet to be properly assessed.
Novel Tissue Engineering Strategies
Stimulation of Repair by Bioactive Factors
The integrity of articular cartilage relies on a fine-tuned local release of hormones, growth
factors and cytokines produced by chondrocytes themselves. By interacting with each other,
these factors control important chondrocyte functions, including cell division, matrix synthe-
sis and degradation. Since cartilage is not vascularised, the autocrine/paracrine network is the
main, if not the only, warrant of the tissue homeostasis. When articular cartilage is injured, this
equilibrium becomes unbalanced. Chondrocytes respond to injury by proliferating and in-
creasing the synthesis of matrix molecules at the edge of the lesion. However, this response is
transient and very soon ceases possibly due to a lack of sustained supply of factors. 9
Molecular therapy, by contrast to the cell-based therapy already used in clinic, is a new
emerging field to repair cartilage damage. The introduction of functional proteins (e.g., growth
factors, signalling molecules, transcription factors and other effectors) at the site of the defect