A systematic review of preclinical in vivo testing of 3D printed porous Ti6Al4V for orthopedic applications, part I: Animal models and bone ingrowth outcome measures

Abstract

For Ti6Al4V orthopedic and spinal implants, osseointegration is often achieved using complex porous geometries created via additive manufacturing (AM). While AM porous titanium (pTi) has shown clinical success, concerns regarding metallic implants have spurred interest in alternative AM biomaterials for osseointegration. Insights regarding the evaluation of these new materials may be supported by better understanding the role of preclinical testing for AM pTi. We therefore asked: (a) What animal models have been most commonly used to evaluate AM porous Ti6Al4V for orthopedic bone ingrowth; (b) What were the primary reported quantitative outcome measures for these models; and (c) What were the bone ingrowth outcomes associated with the most frequently used models? We performed a systematic literature search and identified 58 articles meeting our inclusion criteria. We found that AM pTi was evaluated most often using rabbit and sheep femoral condyle defect (FCD) models. Additional ingrowth models including transcortical and segmental defects, spinal fusions, and calvarial defects were also used with various animals based on the study goals. Quantitative outcome measures determined via histomorphometry including ''bone ingrowth'' (range: 3.92–53.4% for rabbit/sheep FCD) and bone‐implant contact (range: 9.9–59.7% for rabbit/sheep FCD) were the most common. Studies also used 3D imaging to report outcomes such as bone volume fraction (BV/TV, range: 4.4–61.1% for rabbit/sheep FCD), and push‐out testing for outcomes such as maximum removal force (range: 46.6–3092 N for rabbit/sheep FCD). Though there were many commonalities among the study methods, we also found significant heterogeneity in the outcome terms and definitions. The considerable diversity in testing and reporting may no longer be necessary considering the reported success of AM pTi across all model types and the ample literature supporting the rabbit and sheep as suitable small and large animal models, respectively. Ultimately, more standardized animal models and reporting of bone ingrowth for porous AM materials will be useful for future studies.

Bone marrow stromal cells are sensitive to discrete surface alterations in build and post‐build modifications of bioinspired Ti6Al4V 3D‐printed in vitro testing constructs

“…All constructs induce the differentiation of MSCs into osteoblasts over 7 days and that local factor production of MSCs cultured on these Ti6Al4V constructs responds as a result of either build parameters, post‐processing methods, or the combination. These results demonstrate similar robustness in response that correlate well with small and large animal models using M3P implants possessing open‐cell structures 64–66 . Interestingly, Standard build and “50 μm Hatch” with post‐processing by HIP, GB + AE both alter cellular response of MSCs to produce osteogenic local factors in greater concentrations than the other treatments.…”

“…These results demonstrate similar robustness in response that correlate well with small and large animal models using M3P implants possessing open-cell structures. [64][65][66] Interestingly, Standard build and Whereas here, the larger struts create more planar-like surfaces for cells to attach and respond because there may be a lower aspect ratio created by the thicker parts, similar to that of work evaluating cell response to defined fiber diameters.…”

A pH-neutral bioactive glass coated 3D-printed porous Ti6Al4V scaffold with enhanced osseointegration

“…The axial force-displacement curve of the Ti-PSC group was steeper than that of the Ti group at 4 weeks and 8 weeks, that is, to produce the same axial displacement of implant, the needed axial force of the Ti-PSC group was greater. This also indicates that the scaffolds of the Ti-PSC group had greater fixation strength of scaffold and bone, which was a compositive index of osteogenesis, bone in-growth, and osseointegration, and was also an objective expression of the implant stability 39,40 . Therefore, the PSC-coated 3D-printed Ti6Al4Vporous implant is expected to improve the stability of the implant in clinical practice and has a good prospect for clinical application.…”

In vivo study of dual functionalized mussel-derived bioactive peptides promoting 3D-printed porous Ti6Al4V scaffolds for repair of rabbit femoral defects

“…Recently, an emerging metal rapid prototyping technology, Electron Beam Melting (EBM), can realize the fine control of pore parameters and the preparation of porous metal materials with complex shapes. 6 The previous research of the research group showed that different pore size or porosity not only determines that the mechanical properties of the material can match the mechanical properties of the host bone tissue, 7 but also the rough inner and outer surfaces of the porous structure also affect the bone formation at the bone-implant interface. 8,9 When designing the scaffold, the Ti6Al4V scaffold with a pore size of 600 μm was selected, which not only has sufficient mechanical strength, but also promotes bone cell adhesion, proliferation and early differentiation at the same time.…”