The repair of large cranial defects with bone is a major clinical challenge that necessitates novel materials and engineering solutions. Three-dimensionally (3D) printed bioceramic (BioCer) implants consisting of additively manufactured titanium frames enveloped with CaP BioCer or titanium control implants with similar designs were implanted in the ovine skull and at s.c. sites and retrieved after 12 and 3 mo, respectively. Samples were collected for morphological, ultrastructural, and compositional analyses using histology, electron microscopy, and Raman spectroscopy. Here, we show that BioCer implants provide osteoinductive and microarchitectural cues that promote in situ bone regeneration at locations distant from existing host bone, whereas bone regeneration with inert titanium implants was confined to ingrowth from the defect boundaries. The BioCer implant promoted bone regeneration at nonosseous sites, and bone bonding to the implant was demonstrated at the ultrastructural level. BioCer transformed to carbonated apatite in vivo, and the regenerated bone displayed a molecular composition indistinguishable from that of native bone. Proof-of-principle that this approach may represent a shift from mere reconstruction to in situ regeneration was provided by a retrieved human specimen, showing that the BioCer was transformed into well-vascularized osteonal bone, with a morphology, ultrastructure, and composition similar to those of native human skull bone.

用骨头修复大颅骨缺损是一项重大的临床挑战，需要新颖的材料和工程解决方案。将三维（3D）打印的生物陶瓷（BioCer）植入物植入绵羊头骨和sc部位，将其分别包裹在CaP BioCer或钛仿制植入物中，并以类似的设计将其包埋在CaP BioCer或钛对照植入物中，并分别在12 mo和3 mo后取回。使用组织学，电子显微镜和拉曼光谱对样品进行形态，超微结构和组成分析。在这里，我们表明，BioCer植入物提供了骨诱导和微体系结构线索，可促进在距现有宿主骨较远的位置进行原位骨再生，而惰性钛植入物的骨再生仅限于从缺损边界向内生长。BioCer植入物促进了非骨部位的骨再生，并在超微结构水平上证明了骨与植入物的结合。BioCer在体内转化为碳酸磷灰石，并且再生的骨骼显示出与天然骨骼无法区分的分子组成。原理证明，这种方法可能代表了从单纯重建到原位再生的转变，这是由取回的人类标本提供的，表明BioCer已被转化为血管良好的骨质骨，其形态，超微结构和组成类似于天然人类头骨的那些。再生后的骨骼显示出与天然骨骼无法区分的分子组成。原理证明，这种方法可能代表了从单纯重建到原位再生的转变，这是由取回的人类标本提供的，表明BioCer已被转化为血管良好的骨质骨，其形态，超微结构和组成类似于天然人类头骨的那些。再生后的骨骼显示出与天然骨骼无法区分的分子组成。原理证明，这种方法可能代表了从单纯重建到原位再生的转变，这是由取回的人类标本提供的，表明BioCer已被转化为血管良好的骨质骨，其形态，超微结构和组成类似于天然人类头骨的那些。