Toward Biofabrication of Resorbable Implants Consisting of a Calcium Phosphate Cement and Fibrin-A Characterization In Vitro and In Vivo.

Tilman Ahlfeld,Bernd Stadlinger,Winnie Pradel,Martina Rauner,Paula Korn,Michael Gelinsky,Adrian Franke,Günter Lauer,Richard Frank Richter,Anja Lode

doi:10.3390/ijms22031218

Abstract

Cleft alveolar bone defects can be treated potentially with tissue engineered bone grafts. Herein, we developed novel biphasic bone constructs consisting of two clinically certified materials, a calcium phosphate cement (CPC) and a fibrin gel that were biofabricated using 3D plotting. The fibrin gel was loaded with mesenchymal stromal cells (MSC) derived from bone marrow. Firstly, the degradation of fibrin as well as the behavior of cells in the biphasic system were evaluated in vitro. Fibrin degraded quickly in presence of MSC. Our results showed that the plotted CPC structure acted slightly stabilizing for the fibrin gel. However, with passing time and fibrin degradation, MSC migrated to the CPC surface. Thus, the fibrin gel could be identified as cell delivery system. A pilot study in vivo was conducted in artificial craniofacial defects in Lewis rats. Ongoing bone formation could be evidenced over 12 weeks but the biphasic constructs were not completely osseous integrated. Nevertheless, our results show that the combination of 3D plotted CPC constructs and fibrin as suitable cell delivery system enables the fabrication of novel regenerative implants for the treatment of alveolar bone defects.

Highlights

This means that autologous bone grafting material, for example harvested from the iliac crest, is needed and that the patients have to withstand two operations
In order to tackle the problem of homogenous cell seeding of volumetric calcium phosphate cement (CPC) implants, we investigated in this study whether a cell-laden fibrin hydrogel can infiltrate the pores between plotted CPC strands in order to distribute cells homogeneously within a scaffold structure
The fibrin gel successfully filled up the pores of a cubic-shaped CPC scaffold which had a strand-to-strand distance of 2 mm and outer dimensions of 12 × 12 mm2

Summary

Introduction

Cleft lip and cleft alveolus without and with cleft palate belong to the most common congenital craniofacial anomalies in humans. Their development is caused by a malfunction during tissue fusion in embryologic development of the craniomaxillofacial anatomy. Alveolar clefts are treated by primary and especially by secondary bone grafting before teeth eruption [1] This means that autologous bone grafting material, for example harvested from the iliac crest, is needed and that the patients ( young children) have to withstand two operations. Tissue engineering of bone grafts might be a reasonable alternative for the clinical care of alveolar cleft patients, as it avoids one surgical intervention

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