ORTHOPEDIC INTERFACE TISSUE ENGINEERING: BUILDING THE BRIDGE TO INTEGRATED MUSCULOSKELETAL TISSUE SYSTEMS - Advanced Biomaterials: Fundamentals, Processing, and Applications - page 580

controlled matrix heterogeneity minimizes the formation of stress concentrations,
enabling the transfer of complex loads between two distinct types of tissue
(Benjamin, Evans, and Copp 1986; Woo et al. 1983). Current soft tissue recon-
struction methods utilizing autologous or allogeneic grafts unfortunately fail to
preserve or reform the native soft tissue-to-bone insertion, and the absence of
this critical interface compromises graft function and long-term clinical outcome.
Moreover, tissue engineered grafts for soft tissue repair or regeneration also face
similar challenges in graft-to-bone integration.
For interface tissue engineering, it is essential to devise rational strategies
aimed at regenerating the soft tissue-to-bone interface, and subsequently apply-
ing these tissue engineering strategies to design integrative fi xation devices
capable of promoting the biological fi xation of soft tissue grafts to bone. Using
the anterior cruciate ligament (ACL) as a model system, strategies for the regen-
eration of a biomimetic interface between ACL reconstruction grafts and sub-
chondral bone have been formulated (Lu and Jiang 2006). The ACL is the primary
knee joint stabilizer and inserts into bone through a characteristic fi brocartilage
interface, with controlled spatial variations in cell type and matrix composition
(Benjamin, Evans, Rao, Findlay, and Pemberton 1991; Benjamin, Evans, and Copp
1986; Cooper and Misol 1970; Messner 1997; Niyibizi, Visconti, Kavalkovich,
and Woo 1995; Niyibizi, Sagarrigo, Gibson, and Kavalkovich 1996; Petersen and
Tillmann 1999; Sagarriga, Kavalkovich, Wu, and Niyibizi 1996; Thomopoulos,
Williams, Gimbel J.A., Favata, and Soslowsky 2003; Wang, Mitroo, Chen, Lu, and
Doty 2006 ; Wei and Messner 1996 ). The ACL - to - bone junction consists of three
distinct tissue regions: ligament, fi brocartilage, and bone (Figure 17.1).

(a) (b) (c)

Figure 17.1. Multi-tissue Matrix Organization at the Ligament-to-Bone Insertion. A) The
anterior cruciate ligament (ACL) connects the femur and tibia through two insertion sites
(anterior view). B) The multi-tissue organization of the ACL-to-bone insertion, transiting from
the ACL to the fi brocartilage (FC) region, and then to the bone region (Modifi ed Goldner's Masson
Trichrome). C) The fi brocartilage interface is further divided into the non-mineralized fi bro-
cartilage (NFC) and mineralized fi brocartilage (MFC) zones (von Kossa).