Injury to the articular surface, when left untreated, can lead to early onset of osteoarthritis. Repair technology such as Autologous Chondrocyte Transplantation (ACT) is among the first examples of Tissue Engineering (TE) but encounters several drawbacks, i.a. variability in tissue quality, costs and complex logistics. In both ACT and Autologous osteochondral grafting, cartilage is harvested from the joint and thus adverse effects to joint homeostasis must be considered. We recently developed a novel method to generate chondrogenic tissue in vivo: the in situ incubator (ISI). ISI involves creating a space between bone and periosteum, this space is filled by a biogel to generate extra-articular cartilage and thereby differs radically from current Tissue Engineering techniques. In preliminary studies, we found that by simply altering the environment of the ISI, e.g. by induction of hypoxia by local delivery of Suramin, cartilage generation is favored (Fig. 1). An ex vivo model has been optimized in which a whole graft of undifferentiated periosteum is embedded in agarose and stimulated to chondrogenesis. This model enables us to study environmental factors (growth factors, cytokines, oxygen and pharmaceutics etc.) needed to further evaluate this novel technology of de novo cartilage formation using the ISI and to shed light on what biogel characteristics favorably direct the ISI toward chondrogenesis. The overall aim is to improve our understanding what conditions influence succesrate, quality and quantity of cartilage generated in the ISI and to uncover the full therapeutic potential of the "in situ incubator" concept for tissue engineering of cartilage.
Figure:
(A) Extra-articular cartilage (ec) located distally from the rabbit knee (k).
(B) The total amount of extra-articular cartilage formed is approx. 1 cm in diameter. Note 2 grafts of 3 mm in diameter were cored out.
(C-F) Safarin-O stained sections of tissue formed in the In Situ Incubator.
(C) Cartilage formation after injection with HA + liposomes.
(D) Aspecific tissue reaction after injection with agarose/PRP. Note that no cartilage is formed
(E) Cartilage formation after injection with agarose only. The gap indicated by * is probably caused during harvest of the extra-articular cartilage.
(F) Is an enlargement of the box in (E).
Original magnification (C) 25X; (D) 100X; (E) 50X; (F) 200X
Research group
Dr. L.W. van Rhijn, projectleader
Dr. J.W. Voncken
Prof.Dr. R.G.T. Geesink
P. Deckers
N. Guldemond
V.P. Shastri (Vanderbilt, Nashville, TN)
Post-doctoral fellows
Dr. T.J.M. Welting
PhD Students
E.J.P. Jansen
P.J. Emans
F. Spaapen
Technicians
D.A.M. Surtel
A. Cremers
G. M. Wetzels
Students
N. Wijnands
D. v Iersel