<b>UTILITY AND EFFICACY OF HUMAN TISSUE XENOGRAFT IN BONE HEALING</b>
Creators: name: Ganguly, Upasana
Publisher: name: Purdue University Graduate School
Year: 2025
Subjects: classificationCode: 320216
subject: Orthopaedics

description: Connective Tissue Matrix (CTM) allografts are structural implants intended to supplement or replace damaged or inadequate tissues. Generated from human amnion, chorion, and umbilical elements, these allografts contain structural proteins as well as tissue-specific and –agnostic growth factors. In these studies, we examined the efficacy of CTM allografts to improve bone healing and whether CTM alters injury-associated pain behaviors in a pre-clinical animal model.The study involved two surgery models: a surgically induced femoral fracture model and a segmental bone defect (SBD) model. In the femoral fracture model, 12-week-old male C57BL/6J mice were divided into four groups: Saline Control, CTM Membrane, CTM Paste, and CTM Membrane + Paste. For the SBD model, the same age strain of male mice was divided into five groups: Saline Control, BMP-2, CTM Paste, CTM Membrane, and CTM Membrane + Paste.Complete blood count analysis demonstrated no significant alterations in blood cell numbers due to CTM treatments in the femoral fracture model. Despite the presence of various pro-inflammatory cytokines and growth factors in CTM, treated mice showed no significant increase in pain-associated behaviors post-fracture. Bioluminescence imaging demonstrated a significant reduction in inflammation for the CTM Membrane + Paste group on day 14 post-surgery. µCT analysis indicated significant improvement in the mineralized callus area for the CTM Membrane + Paste group when compared to all the other groups in the surgically induced femoral fracture model. Histomorphometric analysis further supported these findings, revealing an increased bone percentage in the callus area for CTM Membrane + Paste group compared to Saline controls in the surgical fracture model. However, biomechanical testing indicated no significant differences between Saline Control and the CTM treated groups. Interestingly, an increasing trend was observed in stiffness and toughness for the CTM Membrane group.Surgical fracture, being a simpler model of fracture, and heal without intervention with time. Hence, that led us to test our hypothesis that CTM products can promote bone healing in a more difficult model, of SBD mice. Long-term evaluations at 13 weeks for the SBD model showed that the BMP-2 group significantly increased the callus area compared to saline controls, with increasing trends observed in CTM-treated groups. Biomechanical testing demonstrated an increasing trend in the ultimate torque in all the groups when compared to Saline Control.Overall, the CTM Membrane + Paste group demonstrated promising potential in enhancing bone healing and reducing inflammation in the surgical fracture model, without triggering additional pain behaviors. The findings from the SBD model revealed that CTM Membrane + Paste has similar impact on bone healing, as observed in the surgical fracture model. Specifically, having a larger callus area as compared to Saline Control group and a significantly higher bone volume / tissue volume (BV/TV) percentage compared to all the other groups. These preclinical findings suggest that CTM allografts may promote fracture repair, providing rationale for further investigations, including a randomized controlled trial for human fractures in weightbearing bones.