Pore size directs bone marrow stromal cell fate and tissue regeneration in nanofibrous macroporous scaffolds by mediating vascularization

Abstract

In the U.S., 30% of adults suffer joint pain, most commonly in the knee, which severely limits mobility and is often attributed to injury of cartilage and underlying bone in the joint. Current treatment methods such as microfracture result in less resilient fibrocartilage with eventual failure; autografting can cause donor site morbidity and poor integration. To overcome drawbacks in treatment, tissue engineers can design cell-instructive biomimetic scaffolds using biocompatible materials as alternate therapies for osteochondral defects. Nanofibrous poly (L-lactic acid) (PLLA) scaffolds of uniform, spherical, interconnected and well-defined pore sizes that are fabricated using a thermally-induced phase separation and sugar porogen template method create an extracellular matrix-like environment which facilitates cell adhesion and proliferation. Herein we report that chondrogenesis and endochondral ossification of rabbit and human bone marrow stromal cells (BMSCs) can be controlled by scaffold pore architecture, particularly pore size. Small-pore scaffolds support enhanced chondrogenic differentiation in vitro and cartilage formation in vivo compared to large-pore scaffolds. Endochondral ossification is prevented in scaffolds with very small pore sizes; pore interconnectivity is critical to promote capillary ingrowth for mature bone formation. These results provide a novel strategy to control tissue regenerative processes by tunable architecture of macroporous nanofibrous scaffolds.

3D printing of shape memory poly(d,l‐lactide‐co‐trimethylene carbonate) by direct ink writing for shape‐changing structures

“…. Besides, large pore size has the advantage of benefiting infiltration and permeability of blood and nutrition into the fabric, promoting its vascularization . Furthermore, higher porosity ratio corresponds to higher specific surface, which could improve the interaction between the fabric and the physiological environment.…”

Effect of the nano/microscale structure of biomaterial scaffolds on bone regeneration

“…7 The advantages of pores have been described in the numerous studies; they allow for osteoblasts migration and proliferation, the transport of nutrients and waste, 7,107,108 and vascularization. 109 Hence, well-interconnected pore structures could facilitate cell infiltration and the transportion of nutrient and nutritions and waste. 110 Usually, scaffolds must be post-processed after their initial fabrication to develop a porous structure.…”

Designing Microgels for Cell Culture and Controlled Assembly of Tissue Microenvironments

“…[24] This aligns with a growing body of literature demonstrating that microenvironmental structure and porosity can have significant effects on cell function and phenotypic changes in 3D scaffolds. [145][146][147][148][149] The facile nature of controlling scaffold porosity in microgel assembled scaffolds makes them ideal candidates to further explore these effects.…”