A biomaterial with a channel-like pore architecture induces endochondral healing of bone defects

A Petersen,K Schmidt-Bleek,S Geissler,A Ellinghaus,G N Duda,A Woloszyk,A Princ,G Korus,I Heschel,H Leemhuis,S Schreivogel,A Klaumünzer,A Herrera

doi:10.1038/s41467-018-06504-7

Abstract

Biomaterials developed to treat bone defects have classically focused on bone healing via direct, intramembranous ossification. In contrast, most bones in our body develop from a cartilage template via a second pathway called endochondral ossification. The unsolved clinical challenge to regenerate large bone defects has brought endochondral ossification into discussion as an alternative approach for bone healing. However, a biomaterial strategy for the regeneration of large bone defects via endochondral ossification is missing. Here we report on a biomaterial with a channel-like pore architecture to control cell recruitment and tissue patterning in the early phase of healing. In consequence of extracellular matrix alignment, CD146+ progenitor cell accumulation and restrained vascularization, a highly organized endochondral ossification process is induced in rats. Our findings demonstrate that a pure biomaterial approach has the potential to recapitulate a developmental bone growth process for bone healing. This might motivate future strategies for biomaterial-based tissue regeneration.

Highlights

Biomaterials developed to treat bone defects have classically focused on bone healing via direct, intramembranous ossification
To gain information about the structural organization of the extracellular matrix (ECM), we first characterized the appearance of collagen fibers in criticalsize segmental bone defects in rats via second harmonic imaging (SHI) in the absence of any biomaterial
We speculated that the specific ECM pattern that initially develops in critical-size segmental bone defects functions as a physical barrier that hinders endochondral bone regeneration

Summary

Introduction

Biomaterials developed to treat bone defects have classically focused on bone healing via direct, intramembranous ossification. Our findings demonstrate that a pure biomaterial approach has the potential to recapitulate a developmental bone growth process for bone healing This might motivate future strategies for biomaterial-based tissue regeneration. We were able to show that a biomaterial, engineered to provide mechanical properties similar to the natural ECM together with a unique channel-like macroporous architecture, enabled a structurally guided EO process across the bone defect. This was achieved by a consistent, material-controlled realignment of collagen fibers across the bone defect associated with enhanced progenitor cell recruitment. In light of translational applications such an approach is highly desirable, as it omits the need for growth factor or cell delivery[33]

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Results

Conclusion