Engineering Orthopedic Tissue Interfaces

Abstract

While a wide variety of approaches to engineering orthopedic tissues have been proposed, less attention has been paid to the interfaces, the specialized areas that connect two tissues of different biochemical and mechanical properties. The interface tissue plays an important role in transitioning mechanical load between disparate tissues. Thus, the relatively new field of interfacial tissue engineering presents new challenges--to not only consider the regeneration of individual orthopedic tissues, but also to design the biochemical and cellular composition of the linking tissue. Approaches to interfacial tissue engineering may be distinguished based on if the goal is to recreate the interface itself, or generate an entire integrated tissue unit (such as an osteochondral plug). As background for future efforts in engineering orthopedic interfaces, a brief review of the biology and mechanics of each interface (cartilage-bone, ligament-bone, meniscus-bone, and muscle-tendon) is presented, followed by an overview of the state-of-the-art in engineering each tissue, including advances and challenges specific to regenerating the interfaces.

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

“…There are limited studies for multiple tissue regeneration and interfacial tissue integration for functional constructs of neogenic complexes such as ligament bone or cartilage bone. 5,6,25,44 In recent studies, multi-phasic scaffolds or physical gradient constructs have been investigated as vehicles for facilitating multiple tissue formation within a single system, 7,8 as well as bioactive molecule-induced tissue morphogenesis. 9 Various in vitro approaches emphasize the strong potential of geometric control for tissue regeneration and morphogenesis with diverse types of cells.…”

“…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.…”

Three-Dimensional Printed Multiphase Scaffolds for Regeneration of Periodontium Complex

“…Cell-seeded multiphase scaffolds were cultured in 12-well plates for 2 days before in vivo implantation or cultured for 4 weeks in vitro in chemically defined media, a 1:1 mixture of osteo-/odontogenic supplements and fibroblastic differentiation supplements as per our previous methods. 31,34,46 Total 10 samples per group were cultured for in vivo experiments.…”

“…31,34,46 All isolated RNA samples were reverse-transcribed using a kit (Applied Biosystems). For mRNA quantification, real-time quantitative polymerase chain reaction (PCR) with the cDNA samples were performed using ViiAÔ 7 Real-Time PCR System and TaqMan Ò gene expression assays (Applied Biosystems).…”

Multiphase Biodegradable Scaffolds for Tissue Engineering a Tendon-Bone Junction

“…Thus, one of the most immediate challenges facing the field of regenerative medicine is "Interfacial Tissue Engineering" (ITE), which addresses the question of how to generate a multiple tissue junction such as a tendon-bone interface which has integrity, continuity and consists of at least two different yet contiguous types of cells, including tenocytes and osteoblasts [1]. Research to date has taken the approach that it is necessary to use pluripotent stem cells or to co-culture the two dissimilar cell lines either sequentially or together in a single compromised media and under coculture conditions [1,[3][4][5]. This simplistic approach assumes that a tissue junction consists of only two types of cells that join at the interface.…”