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.

Selective laser melting (SLM) is one methodology to realize additive manufacturing and is mainly used to join metal powder in a layer-by-layer manner to produce a solid three-dimensional (3D) object. For bone tissue engineering purposes, scaffolds can readily be designed as 3D data model and realized with titanium known for its excellent osseointegration behavior. The microarchitecture, that is, design with submillimeter features, of additively manufactured scaffolds is in many cases a lattice structure. This study aimed to apply SLM that allows a high degree of microarchitectural freedom to generate lattice structures and to determine the optimal distance between rods and the optimal diameter of rods for osteoconduction (bone ingrowth into scaffolds) and bone regeneration. For the biological readout, diverse SLM-fabricated titanium implants were placed in the calvarium of rabbits and new bone formation and defect bridging were determined after 4 weeks of healing. The results from the middle section of the defects show that with a lattice microarchitecture, the optimal distance between titanium rods is around 0.8 mm and the optimal rod dimension is between 0.3 and 0.4 mm to optimize defect bridging and bone regeneration.