Abstract

Additive manufacturing is a key technology required to realize the production of a personalized bone substitute that exactly meets a patient’s need and fills a patient-specific bone defect. Additive manufacturing can optimize the inner architecture of the scaffold for osteoconduction, allowing fast and reliable defect bridging by promoting rapid growth of new bone tissue into the scaffold. The role of scaffold microporosity/nanoarchitecture in osteoconduction remains elusive. To elucidate this relationship, we produced lithography-based osteoconductive scaffolds from tricalcium phosphate (TCP) with identical macro- and microarchitecture, but varied their nanoarchitecture/microporosity by ranging maximum sintering temperatures from 1000 °C to 1200 °C. After characterization of the different scaffolds’ microporosity, compression strength, and nanoarchitecture, we performed in vivo studies that showed that ingrowth of bone as an indicator of osteoconduction significantly decreased with decreasing microporosity. Moreover, at the 1200 °C peak sinter temperature and lowest microporosity, osteoclastic degradation of the material was inhibited. Thus, even for wide-open porous TCP-based scaffolds, a high degree of microporosity appears to be essential for optimal osteoconduction and creeping substitution, which can prevent non-unions, the major complication during bone regeneration procedures.

Highlights

  • Osteoconduction is defined as a process of ingrowth of sprouting capillaries, perivascular tissue, and osteoprogenitor cells from a bony bed into the 3D structure of a porous implant used as a cue to guide bridging of a defect in bony tissue [3]

  • The low mechanical challenge posed in the cranium is an advantage for testing diverse micro- and nanoarchitectures, since it allows for testing without the need for costly fracture fixation devices, which is indispensable in long bone defect treatments

  • This is in keeping with our results on osteoconduction and bone regeneration, since we detected no significant difference in these parameters when comparing scaffolds sintered at 1100 ◦C with a microporosity of 22% and a grain size of 1.2 μm with those sintered at 1200 ◦C with a microporosity of 1% and a grain size of 3.1 μm

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Summary

Introduction

Osteoconduction is defined as a process of ingrowth of sprouting capillaries, perivascular tissue, and osteoprogenitor cells from a bony bed into the 3D structure of a porous implant (from Cornell and Lane [1,2]) used as a cue to guide bridging of a defect in bony tissue [3]. Observations of osteoconduction were based on transplantation of autologous bone. The initial approaches to define the ideal osteoconductive microarchitecture were undertaken in the 1990s, utilizing scaffolds with randomly distributed pores and channel-based microarchitectures to mimic autologous bone. Based on those findings, pore diameters of 0.3–0.5 mm have long been falsely regarded as optimal for osteoconduction [4,5]. Scaffolds with pore diameters of up to 0.5 mm and beyond 1.5 mm were found to be far less osteoconductive, in that they displayed substantially decelerated defect bridging, which is an indirect measure of osteoconduction [6]. Cranial defects are clinically highly relevant in congenital anomalies, trauma, stroke, aneurysms, and cancer [13]

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