Evaluating the usage of human placental tissue-derived xenograft in a surgically induced murine fracture model.

Abstract

Impaired bone fracture healing can lead to chronic pain, loss of function, or life-long complications which can lead to limb-amputation. This study evaluated the effectiveness of human placental tissue-derived xenograft preparations (Connective Tissue Matrix, [CTM Biomedical®]) in promoting bone healing and reducing post-fracture pain behaviors using a preclinical, surgically induced, murine fracture model. CTM is thought to contain structural proteins and growth factors important for fracture healing. An intramedullary nail was used to stabilize the femur, and a mid-shaft femoral fracture was induced in 12-week-old male C57BL/6 J mice. Mice were divided into four groups (Saline Control, CTM Membrane, CTM Paste, and CTM Membrane + Paste). Complete blood count (CBC) and pain behavioral assessments were performed weekly. Modified radiographic union for tibial fracture (mRUST) scoring was used to assess healing from bi-weekly X-rays. Mice were euthanized 23 days post-fracture (dpf), and femurs were collected for μCT analysis and biomechanical or histomorphometric analyses. No significant changes in CBC were observed in any group. Compared to Saline Control, CTM Membrane (p = 0.002) and CTM Membrane + Paste (p = 0.04) treated groups exhibited a reduced pain score 4 dpf (grimace scores). μCT and histomorphometry showed that CTM Membrane + Paste group had significantly higher callus area (p = 0.01) and % bone (p = 0.001) compared to Saline Controls. mRUST scores, endomucin staining, and biomechanical outcomes between groups were not different. Preclinical findings suggest that CTM Membrane + Paste exhibits potential in enhancing bone healing. CTM products also do not increase pain behaviors in the surgical fracture model.