In situ bone regeneration of large cranial defects using synthetic ceramic implants with a tailored composition and design

Author:

Omar OmarORCID,Engstrand ThomasORCID,Kihlström Burenstam Linder LarsORCID,Åberg JonasORCID,Shah Furqan A.ORCID,Palmquist AndersORCID,Birgersson UlrikORCID,Elgali Ibrahim,Pujari-Palmer MichaelORCID,Engqvist HåkanORCID,Thomsen PeterORCID

Abstract

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.

Funder

BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy

Vastra Gotaland Region

Swedish Research Council

Swedish Foundation for Strategic Research

Swedish state under the agreement between the Swedish government and the county councils, the ALF agreement

IngaBritt and Arne Lundberg Foundation

Hjalmar Svensson Foundation

Adlerbertska Foundation

Sylvan Foundation

Area of Advance Materials of Chalmers and GU Biomaterials within the Strategic Research Area initiative launched by the Swedish government

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

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