Preclinical Safety of a 3D-Printed Hydroxyapatite-Demineralized Bone Matrix Scaffold for Spinal Fusion

Abstract

Study Design. Prospective, randomized, controlled preclinical study.Objective. The objective of this study was to compare the host inflammatory response of our previously described hyperelastic, 3D-printed (3DP) hydroxyapatite (HA)-demineralized bone matrix (DBM) composite scaffold to the response elicited with the use of recombinant human bone morphogenetic protein-2 (rhBMP-2) in a preclinical rat posterolateral lumbar fusion model. Summary of Background Data. Our group previously found that this 3D-printed HA-DBM composite material shows promise as a bone graft substitute in a preclinical rodent model, but its safety profile had yet to be assessed. Methods. Sixty female Sprague-Dawley rats underwent bilateral posterolateral intertransverse lumbar spinal fusion using with the following implants: 1) type I absorbable collagen sponge (ACS) alone; 2) 10 mg rhBMP-2/ACS; or 3) the 3DP HA-DBM composite scaffold (n ¼ 20). The host inflammatory response was assessed using magnetic resonance imaging, while the local and circulating cytokine expression levels were evaluated by enzyme-linked immunosorbent assays at subsequent postoperative time points (N ¼ 5/time point). Results. At both 2 and 5 days postoperatively, treatment with the HA-DBM scaffold produced significantly less soft tissue edema at the fusion bed site relative to rhBMP-2-treated animals as quantified on magnetic resonance imaging. At every postoperative time point evaluated, the level of soft tissue edema in HA-DBM-treated animals was comparable to that of the ACS control group. At 2 days postoperatively, serum concentrations of tumor necrosis factor-a and macrophage chemoattractant protein-1 were significantly elevated in the rhBMP-2 treatment group relative to ACS controls, whereas these cytokines were not elevated in the HA-DBM-treated animals. Conclusion. The 3D-printed HA-DBM composite induces a significantly reduced host inflammatory response in a preclinical spinal fusion model relative to rhBMP-2.

Advantages of Using 3D Spheroid Culture Systems in Toxicological and Pharmacological Assessment for Osteogenesis Research

“…Recently, bone studies using 3D culture systems have become instrumental in advancing regenerative medicine. Researchers can engineer tissue constructs using 3D scaffolds and stem cells to offer promising solutions for bone repair and replacement [ 47 , 48 ]. These tissue-engineered constructs can be tailored to match a patient’s anatomy, reduce graft rejection risk, and improve the overall success rate of bone graft implantation.…”

“…It is recognized that 3D bone culture systems can be employed to study the molecular mechanisms underlying osteogenesis, screen drug candidates for bone-related disorders, and develop bone-tissue-engineered constructs for bone repair and regeneration. Additionally, the integration of advanced technologies, such as 3D bioprinting and microfluidics, holds promise for further advancing the field of bone differentiation in 3D culture systems [ 47 , 140 ]. In 3D cultures, the diffusion of nutrients and oxygen is limited as the size of the culture increases [ 141 ].…”

Biomaterials of human source for 3D printing strategies

“…There are several studies following the rationale of having synthetic polymeric support for depositing the natural inks in-between the synthetic filaments (figure 5(a)), providing mechanical support while the matrices undergo reticulation [118,119,242,243]. Other authors mixed PLGA with tissue-specific ECM and HA to act as an ink binder for extrusion printing (figure 5(b)), which demonstrated being a valuable scaffold for spine fusion [239][240][241]. 3D printed PCL was also used to provide different mechanical proprieties to multilayer constructs with human-derived keratin intercalating the PCL layers (figure 5(c)), which demonstrated high dermal regenerative capacity compared with bare PCL controls [147].…”

Customized Additive Manufacturing in Bone Scaffolds—The Gateway to Precise Bone Defect Treatment

“…Materials like demineralized bone matrices and HAP are being utilized due to their inherent growth factors and osteogenic substances [ 139 ]. Composite materials incorporating these elements have shown reduced inflammatory responses and improved fusion results [ 140 , 141 ]. Implants printed with PLA and nHAP can be mechanically tuned, showing great customization potential [ 142 ].…”