^{In VivoModels for the Evaluation of the Osteogenic Potency of Bone Substitutes Seeded with Mesenchymal Stem Cells of Human Origin: A Concise Review}

Abstract

Research concerning bone substitutes is one of the most challenging fields in orthopedic research and has a high clinical relevance, especially since the currently available bone substitutes are limited in their osteostimulative capabilities. In vitro models for the evaluation of the properties of bone substitutes allow the use of human mesenchymal stem cells (hMSCs) seeded onto scaffolds, but suffer from the lack of a physiological environment for those cells. Most in vivo models include the use of non-hMSC and are therefore lacking in clinical relevance. To overcome these issues, in vivo models were created that allow the evaluation of hMSC-seeded bone substitutes, combining the advantages of the use of human cells with the physiological conditions of an organism in vivo. In brief, models usually aim for bone formation in immunocompromised rodents. The subcutaneous implantation of scaffolds is most widely performed, showing low complication rates along with good results, but suffering from inferior vascularization of the implants and the absence of the realistic structural and mechanical conditions of bone. Orthotopic implantation, for example in calvarian or long bone defects, provides the most appropriate surrounding for hMSC-seeded scaffolds. However, parallel host-induced bone formation is a major limitation. This review summarizes in vivo models for the evaluation of the osteogenic potency of bone substitutes seeded with mesenchymal stem cells of human origin.

Combining advantages: Direct correlation of two‐dimensional microcomputed tomography datasets onto histomorphometric slides to quantify three‐dimensional bone volume in scaffolds

“…To prove our method, we used data acquired by a well‐established model for in vivo analysis of bone substitutes . By addition of BMP‐7 to ß‐TCP‐scaffolds, bone formation within the scaffold can be enhanced as demonstrated previously .…”

“…In this case, relative bone volume was nonsignificantly smaller than the percentage bone amount in 2D mCT evaluation and histomorphometry. This may be caused by the selection of “optimal” locations of a scaffold in cutting for histomorphometry preparation, as well as the assumption that due to the mechanical conditions of the in vivo model we used, bone formation most likely takes place in the porous center of the scaffold and not on the boundaries, which are less influenced by mechanical stress …”

“…What can be detected in histomorphometry is a calcified, osteoid‐like structure defined as precursor of bone tissue around the scaffold material . The missing clear anatomical correlates of calcified tissue in scaffolds make a direct identification of the respective region of interest (ROI) in mCT difficult, because these structures cannot be clearly identified by their morphological correlates as would be possible in actual bone …”

Gelatin‐coating increases in‐vivo bone formation capacity of three‐dimensional 45S5‐bioactive glass‐based crystalline scaffolds

“…Synthetic bone substitutes are frequently used for several applications in orthopaedic surgery (Giannoudis, Dinopoulos, & Tsiridis, ). The most common bone scaffold materials are calcium phosphate ceramics, such as tricalcium phosphates or hydroxyapatites (Janicki & Schmidmaier, ; Westhauser, Senger, Reible, & Moghaddam, ). However, these materials show some limitations regarding biological properties, such as limited stimulation of bone formation within the scaffold structure, that are mostly linked to morphological characteristics such as porosity or surface area (Cao & Hench, ; Janicki & Schmidmaier, ).…”

“…In addition, the effect of gelatin surface coating on both osteogenic properties and mechanical features has not been investigated previously. In this study, uncoated (Group A) and gelatin‐coated (Group B) 3D BG‐based scaffolds obtained from S. agaricina as a template, seeded with human bone marrow‐derived MSCs (hBMSC), are evaluated concerning osteogenic properties using an established in vivo model (Westhauser, Senger, et al, ). Bone formation is quantified by non‐invasive micro‐computed tomography (mCT) evaluation and assessed both quantitatively and qualitatively by histomorphometry (Westhauser, Senger, et al, ; Westhauser, Weis, et al, ).…”