Browsing by Author "Beucken, Jeroen J.J.P. van den"

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    Repair of complex ovine segmental mandibulectomy utilizing customized tissue engineered bony flaps
    (Public Library of Science, 2023) Watson, Emma; Pearce, Hannah A.; Hogan, Katie J.; Dijk, Natasja W.M. van; Smoak, Mollie M.; Barrios, Sergio; Smith, Brandon T.; Tatara, Alexander M.; Woernley, Timothy C.; Shum, Jonathan; Pearl, Craig B.; Melville, James C.; Ho, Tang; Hanna, Issa A.; Demian, Nagi; Beucken, Jeroen J.J.P. van den; Jansen, John A.; Wong, Mark E.; Mikos, Antonios G.
    Craniofacial defects require a treatment approach that provides both robust tissues to withstand the forces of mastication and high geometric fidelity that allows restoration of facial architecture. When the surrounding soft tissue is compromised either through lack of quantity (insufficient soft tissue to enclose a graft) or quality (insufficient vascularity or inducible cells), a vascularized construct is needed for reconstruction. Tissue engineering using customized 3D printed bioreactors enables the generation of mechanically robust, vascularized bony tissues of the desired geometry. While this approach has been shown to be effective when utilized for reconstruction of non-load bearing ovine angular defects and partial segmental defects, the two-stage approach to mandibular reconstruction requires testing in a large, load-bearing defect. In this study, 5 sheep underwent bioreactor implantation and the creation of a load-bearing mandibular defect. Two bioreactor geometries were tested: a larger complex bioreactor with a central groove, and a smaller rectangular bioreactor that were filled with a mix of xenograft and autograft (initial bone volume/total volume BV/TV of 31.8 ± 1.6%). At transfer, the tissues generated within large and small bioreactors were composed of a mix of lamellar and woven bone and had BV/TV of 55.3 ± 2.6% and 59.2 ± 6.3%, respectively. After transfer of the large bioreactors to the mandibular defect, the bioreactor tissues continued to remodel, reaching a final BV/TV of 64.5 ± 6.2%. Despite recalcitrant infections, viable osteoblasts were seen within the transferred tissues to the mandibular site at the end of the study, suggesting that a vascularized customized bony flap is a potentially effective reconstructive strategy when combined with an optimal stabilization strategy and local antibiotic delivery prior to development of a deep-seated infection.
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    Tunable calcium phosphate cement formulations for predictable local release of doxycycline
    (Elsevier, 2023) Liu, Qian; Lodoso-Torrecilla, Irene; Gunnewiek, Raquel Klein; Harhangi, Harry R.; Mikos, Antonios G.; van Niftrik, Laura; Jansen, John A.; Chen, Lili; Beucken, Jeroen J.J.P. van den
    Background Osteomyelitis is a bacterial infection, which leads to bone loss. Local treatment focuses on elimination of bacteria, which is preferable for simultaneous management of the bone defect after sequestrectomy and bone reconstruction in one-stage treatment of osteomyelitis. Calcium phosphate cements (CPCs) have attracted increased attention as bone substitute material because of their injectability and in situ self-setting properties, which allow for minimally invasive surgical procedures and local drug delivery. Methods We herein established a system to achieve different release profiles of the antibiotic drug doxycycline from CPC by finetuning their formulation. These CPC formulations were generated via facile addition of hydrolytically degrading PLGA particles, varying doses of doxycycline, and addition of the lubricant CMC. Results The CPC formulations exhibited appropriate handling properties in terms of injectability and setting time. Furthermore, doxycycline release profiles showed an adequate burst release followed by a cumulative release of up to 100% over a period of 8 weeks. Importantly, the released doxycycline retained its antibacterial activity against Staphylococcus aureus, the major pathogen causing osteomyelitis. Using an in vivo implantation model, antibacterial efficacy was demonstrated by a rapid decrease of inoculated S. aureus at the CPC surface and within surrounding tissues. Conclusions Our data show the versatility of the CPC system toward local antibacterial therapy, extending its application beyond bone substitution.