Tissue Engineering Strategies for the Regeneration of Orthopedic Interfaces

Abstract

A major focus in the field of orthopaedic tissue engineering is the development of tissue engineered bone and soft tissue grafts with biomimetic functionality to allow for their translation to the clinical setting. One of the most significant challenges of this endeavor is promoting the biological fixation of these grafts with each other as well as the implant site. Such fixation requires strategic biomimicry to be incorporated into the scaffold design in order to re-establish the critical structure-function relationship of the native soft tissue-to-bone interface. The integration of distinct tissue types (e.g. bone and soft tissues such as cartilage, ligaments, or tendons), requires a multi-phased or stratified scaffold with distinct yet continuous tissue regions accompanied by a gradient of mechanical properties that mimics that of the multi-tissue transition between bone and soft tissues. This review discusses tissue engineering strategies for regenerating common tissue-to-tissue interfaces (ligament-to-bone, tendon-to-bone or cartilage-to-bone), and the strategic biomimicry implemented in stratified scaffold design for multi-tissue regeneration. Potential challenges and future directions in this emerging field will also be presented. It is anticipated that interface tissue engineering will enable integrative soft tissue repair, and will be instrumental for the development of complex musculoskeletal tissue systems with biomimetic complexity and functionality.

Three-Dimensional Printed Multiphase Scaffolds for Regeneration of Periodontium Complex

“…Previous periodontal tissues regeneration models have primarily adopted the approach of staggering multiple layers of biomaterials. 26,[49][50][51] Although staggering of multiple biomaterial sheets is convenient for cell seeding, potential delamination of multiple layers is a concern. The present work takes advantage of our existing approach 33 of continuous 3D printing to construct a seamless biomaterial scaffold and yet with different region-specific pore/channel sizes that are specifically designed for integrated regeneration of multiple periodontal tissues.…”

Image-Based, Fiber Guiding Scaffolds: A Platform for Regenerating Tissue Interfaces

“…1,2 Although regenerative medicine holds promise as a prominent future therapeutic strategy, only a limited number of studies have achieved success in multipletissue regeneration and functional interfacial tissue integration, as evident in ligament-bone or cartilage-bone complexes. [3][4][5][6] To overcome these therapeutic difficulties, multi-phasic scaffolds or physical gradient constructs have been designed and used for multiple tissue formation within a single system 7,8 as well as for bioactive molecule-induced tissue morphogenesis and regeneration. 9 Various in vitro approaches highlight the importance of geometric control on tissue regeneration/ morphogenesis using a variety of cell types, [10][11][12] but geometric influences on spatiotemporal tissue regeneration and functional healing have had limited assessment in vivo.…”

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

“…194 Current design challenges for engineering biomimetic gradients are caused mostly by a question of scale, as it is not an easy task to mimic the micro-and nanoscale gradients reported at tissueto-tissue interfaces, such as the osteochondral one. 195 The application of dual-delivery systems for cartilage regeneration has also been under intensive investigation. Bian et al…”