Human Whole Blood Interactions with Craniomaxillofacial Reconstruction Materials: Exploring In Vitro the Role of Blood Cascades and Leukocytes in Early Healing Events

Author:

Lopes Viviana R.12ORCID,Birgersson Ulrik34ORCID,Manivel Vivek Anand5ORCID,Hulsart-Billström Gry2ORCID,Gallinetti Sara6,Aparicio Conrado78ORCID,Hong Jaan5ORCID

Affiliation:

1. OssDsign AB, SE-754 50 Uppsala, Sweden

2. Department of Medicinal Chemistry, Translational Imaging, Uppsala University, SE-751 83 Uppsala, Sweden

3. Department of Clinical Science, Intervention and Technology, Division of Imaging and Technology, Karolinska Institute, SE-141 52 Huddinge, Sweden

4. Department of Clinical Neuroscience, Neurosurgical Section, Karolinska University Hospital, SE-171 77 Stockholm, Sweden

5. Rudbeck Laboratory, Department of Immunology, Genetics and Pathology (IGP), Uppsala University, SE-751 85 Uppsala, Sweden

6. Department of Engineering Sciences, Applied Materials Science Section, Uppsala University, SE-751 03 Uppsala, Sweden

7. Faculty of Odontology, UIC Barcelona-International University of Catalonia, 08195 Barcelona, Spain

8. IBEC—Institute for Bioengineering of Catalonia, 08028 Barcelona, Spain

Abstract

The present study investigated early interactions between three alloplastic materials (calcium phosphate (CaP), titanium alloy (Ti), and polyetheretherketone (PEEK) with human whole blood using an established in vitro slide chamber model. After 60 min of contact with blood, coagulation (thrombin–antithrombin complexes, TAT) was initiated on all test materials (Ti > PEEK > CaP), with a significant increase only for Ti. All materials showed increased contact activation, with the KK–AT complex significantly increasing for CaP (p < 0.001), Ti (p < 0.01), and PEEK (p < 0.01) while only CaP demonstrated a notable rise in KK-C1INH production (p < 0.01). The complement system had significant activation across all materials, with CaP (p < 0.0001, p < 0.0001) generating the most pronounced levels of C3a and sC5b-9, followed by Ti (p < 0.001, p < 0.001) and lastly, PEEK (p < 0.001, p < 0.01). This activation correlated with leukocyte stimulation, particularly myeloperoxidase release. Consequently, the complement system may assume a more significant role in the early stages post implantation in response to CaP materials than previously recognized. Activation of the complement system and the inevitable activation of leukocytes might provide a more favorable environment for tissue remodeling and repair than has been traditionally acknowledged. While these findings are limited to the early blood response, complement and leukocyte activation suggest improved healing outcomes, which may impact long-term clinical outcomes.

Publisher

MDPI AG

Subject

Biomedical Engineering,Biomaterials

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