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

IF 3.6 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Bone Pub Date : 2025-07-24 DOI:10.1016/j.bone.2025.117599

Upasana Ganguly , Tyler J. Margetts , Will Varner Anou , Murad K. Nazzal , Reginald S. Parker , Hanyu Xia , Ashlyn J. Morris , Abdullahi Warsame , Sarah L. Mostardo , Kuldeep Yadav , Rachel J. Blosser , Istvan Gergely , Aamir Tucker , Sonali J. Karnik , Jiliang Li , David L. Waning , Amy Creecy , Jill C. Fehrenbacher , Melissa A. Kacena

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引用次数: 0

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.

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评估人类胎盘组织来源的异种移植物在手术诱导的小鼠骨折模型中的应用。

骨折愈合受损可导致慢性疼痛、功能丧失或终身并发症，这些并发症可导致截肢。本研究通过临床前、手术诱导的小鼠骨折模型，评估了人类胎盘组织来源的异种移植制剂（结缔组织基质，[CTM Biomedical®]）在促进骨愈合和减少骨折后疼痛行为方面的有效性。CTM被认为含有对骨折愈合很重要的结构蛋白和生长因子。采用髓内钉固定股骨，并在12周龄雄性C57BL/6 J小鼠中诱导股骨中轴骨折。小鼠分为生理盐水对照组、中药膜组、中药膏组、中药膜+膏组。每周进行全血细胞计数（CBC）和疼痛行为评估。改良胫骨骨折x线愈合（mRUST）评分用于评估两周x线的愈合情况。小鼠骨折后（dpf） 23 d安乐死，收集股骨进行μCT分析和生物力学或组织形态学分析。各组CBC均未见明显变化。与生理盐水对照组相比，CTM膜治疗组（p = 0.002）和CTM膜+膏治疗组（p = 0.04）疼痛评分降低4 dpf（鬼脸评分）。μCT和组织形态学分析结果显示，与生理盐水对照组相比，CTM膜+膏组的骨痂面积（p = 0.01）和骨% （p = 0.001）显著增加。各组间mRUST评分、内膜蛋白染色和生物力学结果均无差异。临床前研究结果提示CTM膜+膏具有促进骨愈合的潜力。CTM产品在手术骨折模型中也不会增加疼痛行为。

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来源期刊

Bone 医学-内分泌学与代谢

CiteScore

8.90

自引率

4.90%

发文量

264

审稿时长

30 days

期刊介绍： BONE is an interdisciplinary forum for the rapid publication of original articles and reviews on basic, translational, and clinical aspects of bone and mineral metabolism. The Journal also encourages submissions related to interactions of bone with other organ systems, including cartilage, endocrine, muscle, fat, neural, vascular, gastrointestinal, hematopoietic, and immune systems. Particular attention is placed on the application of experimental studies to clinical practice.