Biomimetic Stratified Scaffold Design for Ligament-to-Bone Interface Tissue Engineering

Abstract

The emphasis in the field of orthopaedic tissue engineering is on imparting biomimetic functionality to tissue engineered bone or soft tissue grafts and enabling their translation to the clinic. A significant challenge in achieving extended graft functionality is engineering the biological fixation of these grafts with each other as well as with the host environment. Biological fixation will require re-establishment of the structure-function relationship inherent at the native soft tissue-to-bone interface on these tissue engineered grafts. To this end, strategic biomimicry must be incorporated into advanced scaffold design. To facilitate integration between distinct tissue types (e.g., bone with soft tissues such as cartilage, ligament, or tendon), a stratified or multi-phasic scaffold with distinct yet continuous tissue regions is required to pre-engineer the interface between bone and soft tissues. Using the ACL-to-bone interface as a model system, this review outlines the strategies for stratified scaffold design for interface tissue engineering, focusing on identifying the relevant design parameters derived from an understanding of the structure-function relationship inherent at the soft-to-hard tissue interface. The design approach centers on first addressing the challenge of soft tissue-to-bone integration ex vivo, and then subsequently focusing on the relatively less difficult task of bone-to-bone integration in vivo. In addition, we will review stratified scaffold design aimed at exercising spatial control over heterotypic cellular interactions, which are critical for facilitating the formation and maintenance of distinct yet continuous multi-tissue regions. Finally, potential challenges and future directions in this emerging area of advanced scaffold design will be discussed.

Mechanical design criteria for intervertebral disc tissue engineering

“…Our discussion thus far has been limited to the NP and AF; however, the cartilaginous endplate plays an important role in nutrient supply and waste removal and forms the interface between the disc and vertebral body. Engineering an interface between two disparate tissues is indeed a complicated problem, and one which is being studied in other tissues (Lu and Spalazzi, 2009; Spalazzi et al, 2006; Yang and Temenoff, 2009) as well as the disc (Hamilton et al, 2006). Upon successful engineering of the disc, it will be important to develop a functional interface with which the construct can be implanted into the disc space without risk of dislocation.…”

Osteochondral interface regeneration of the rabbit knee with macroscopic gradients of bioactive signals

“…Simply, the interface is where two tissue types adjoin. Most approaches directly targeting tissue engineering of interfaces have been stratified in nature, with multiple discrete layers of differing physical or chemical properties 1–15. The approach of using continuously graded 3D designs for interface tissue engineering, as opposed to stratified designs, is gaining attention 16…”

“…Most approaches directly targeting tissue engineering of interfaces have been stratified in nature, with multiple discrete layers of differing physical or chemical properties. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15] The approach of using continuously graded 3D designs for interface tissue engineering, as opposed to stratified designs, is gaining attention. 16 Many groups 4,[16][17][18][19] have compiled comprehensive reviews on state of the art applications for incorporating continuous gradients in tissue engineering, illustrating numerous current and potential strategies for interfacial tissue engineering.…”

Controlled Release Strategies for Bone, Cartilage, and Osteochondral Engineering—Part II: Challenges on the Evolution from Single to Multiple Bioactive Factor Delivery

“…Aberrant inflammation has been implicated as a significant factor in bone injuries that fail to heal; thus, tight control over this process must be tailored. 184 An obvious interesting approach for a multiple delivery system is the regeneration of orthopedic interfaces, such as ligament-to-bone, 185,186 tendon-to-bone, 187 and cartilage-tobone. 188 Many approaches have been used to fabricate scaffolds for osteochondral application by changing material composition, mechanical properties, and architecture between the chondrogenic and osteogenic layers.…”