Protein-spatiotemporal partition releasing gradient porous scaffolds and anti-inflammatory and antioxidant regulation remodel tissue engineered anisotropic meniscus

Meniscus is a wedge-shaped fibrocartilaginous tissue,playing important roles in maintaining joint stability and function.Meniscus injuries are difficult to heal and frequently progress into structural breakdown,which then leads to osteoarthritis.Regeneration of heterogeneous tissue engineering meniscus(TEM)continues to be a scientific and translational challenge.The morphology,tissue architecture,mechanical strength,and functional applications of the cultivated TEMs have not been able to meet clinical needs,which may due to the negligent attention on the importance of microenvironment in vitro and in vivo.Herein,we combined the 3D(three-dimensional)-printed gradient porous scaffolds,spatiotemporal partition release of growth factors,and anti-inflammatory and anti-oxidant microenvironment regulation of Ac2-26 peptide to prepare a versatile meniscus composite scaffold with heterogeneous bionic structures,excellent biomechanical properties and anti-inflammatory and anti-oxidant effects.By observing the results of cell activity and differentiation,and biomechanics under anti-inflammatory and anti-oxidant microenvironments in vitro,we explored the effects of anti-inflammatory and anti-oxidant microenvironments on construction of regional and functional heterogeneous TEM via the growth process regulation,with a view to cultivating a high-quality of TEM from bench to bedside.

3D cell-printing of gradient multi-tissue interfaces for rotator cuff regeneration

Owing to the prevalence of rotator cuff(RC)injuries and suboptimal healing outcome,rapid and functional regeneration of the tendon-bone interface(TBI)after RC repair continues to be a major clinical challenge.Given the essential role of the RC in shoulder movement,the engineering of biomimetic multi-tissue constructs presents an opportunity for complex TBI reconstruction after RC repair.Here,we propose a gradient cell-laden multi-tissue construct combined with compositional gradient TBI-specific bioinks via 3D cell-printing technology.In vitro studies demonstrated the capability of a gradient scaffold system in zone-specific inducibility and multi-tissue formation mimicking TBI.The regenerative performance of the gradient scaffold on RC regeneration was determined using a rat RC repair model.In particular,we adopted nondestructive,consecutive,and tissue-targeted near-infrared fluorescence imaging to visualize the direct anatomical change and the intricate RC regeneration progression in real time in vivo.Furthermore,the 3D cell-printed implant promotes effective restoration of shoulder locomotion function and accelerates TBI healing in vivo.In summary,this study identifies the therapeutic contribution of cell-printed constructs towards functional RC regeneration,demonstrating the translational potential of biomimetic gradient constructs for the clinical repair of multi-tissue interfaces.

Articular cartilage and osteochondral tissue engineering techniques:Recent advances and challenges

In spite of the considerable achievements in the field of regenerative medicine in the past several decades,osteochondral defect regeneration remains a challenging issue among diseases in the musculoskeletal system because of the spatial complexity of osteochondral units in composition,structure and functions.In order to repair the hierarchical tissue involving different layers of articular cartilage,cartilage-bone interface and subchondral bone,traditional clinical treatments including palliative and reparative methods have showed certain improvement in pain relief and defect filling.It is the development of tissue engineering that has provided more promising results in regenerating neo-tissues with comparable compositional,structural and functional characteristics to the native osteochondral tissues.Here in this review,some basic knowledge of the osteochondral units including the anatomical structure and composition,the defect classification and clinical treatments will be first introduced.Then we will highlight the recent progress in osteochondral tissue engineering from perspectives of scaffold design,cell encapsulation and signaling factor incorporation including bioreactor application.Clinical products for osteochondral defect repair will be analyzed and summarized later.Moreover,we will discuss the current obstacles and future directions to regenerate the damaged osteochondral tissues.