Department of Orthopaedic Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California.
SeaSpine Holdings, Carlsbad, California.
J Bone Joint Surg Am. 2020 Dec 16;102(24):e135. doi: 10.2106/JBJS.20.00330.
Despite the extensive use of cellular bone matrices (CBMs) in spine surgery, there is little evidence to support the contribution of cells within CBMs to bone formation. The objective of this study was to determine the contribution of cells to spinal fusion by direct comparisons among viable CBMs, devitalized CBMs, and cell-free demineralized bone matrix (DBM).
Three commercially available grafts were tested: a CBM containing particulate DBM (CBM-particulate), a CBM containing DBM fibers (CBM-fiber), and a cell-free product with DBM fibers only (DBM-fiber). CBMs were used in viable states (CBM-particulatev and CBM-fiberv) and devitalized (lyophilized) states (CBM-particulated and CBM-fiberd), resulting in 5 groups. Viable cell counts and bone morphogenetic protein-2 (BMP-2) content on enzyme-linked immunosorbent assay (ELISA) within each graft material were measured. A single-level posterolateral lumbar fusion was performed on 45 athymic rats with 3 lots of each product implanted into 9 animals per group. After 6 weeks, fusion was assessed using manual palpation, micro-computed tomography (μ-CT), and histological analysis.
The 2 groups with viable cells were comparable with respect to cell counts, and pairwise comparisons showed no significant differences in BMP-2 content across the 5 groups. Manual palpation demonstrated fusion rates of 9 of 9 in the DBM-fiber specimens, 9 of 9 in the CBM-fiberd specimens, 8 of 9 in the CBM-fiberv specimens, and 0 of 9 in both CBM-particulate groups. The μ-CT maturity grade was significantly higher in the DBM-fiber group (2.78 ± 0.55) compared with the other groups (p < 0.0001), while none of the CBM-particulate samples demonstrated intertransverse fusion in qualitative assessments. The viable and devitalized samples in each CBM group were comparable with regard to fusion rates, bone volume fraction, μ-CT maturity grade, and histological features.
The cellular component of 2 commercially available CBMs yielded no additional benefits in terms of spinal fusion. Meanwhile, the groups with a fiber-based DBM demonstrated significantly higher fusion outcomes compared with the CBM groups with particulate DBM, indicating that the DBM component is probably the key determinant of fusion.
Data from the current study demonstrate that cells yielded no additional benefit in spinal fusion and emphasize the need for well-designed clinical studies on cellular graft materials.
尽管细胞骨基质（CBMs）在脊柱手术中被广泛应用，但几乎没有证据表明 CBM 中的细胞对骨形成有贡献。本研究的目的是通过对活 CBMs、失活 CBMs 和无细胞脱矿骨基质（DBM）进行直接比较，来确定细胞对脊柱融合的贡献。
测试了三种市售移植物：一种含有颗粒状 DBM 的 CBM（CBM-particulate）、一种含有 DBM 纤维的 CBM（CBM-fiber）和一种仅含 DBM 纤维的无细胞产品（DBM-fiber）。CBM 以活的状态（CBM-particulatev 和 CBM-fiberv）和失活（冻干）状态（CBM-particulated 和 CBM-fiberd）使用，共 5 组。测量每个移植物材料中的活细胞计数和酶联免疫吸附试验（ELISA）中的骨形态发生蛋白-2（BMP-2）含量。在 45 只无胸腺大鼠中进行了单节段后路腰椎融合术，每组 9 只动物分别植入 3 批每种产品。6 周后，通过手动触诊、微计算机断层扫描（μ-CT）和组织学分析评估融合情况。
2 组具有活细胞的组在细胞计数方面具有可比性，并且两两比较显示 5 组之间的 BMP-2 含量没有显著差异。手动触诊显示 DBM-fiber 标本的融合率为 9/9，CBM-fiberd 标本的融合率为 9/9，CBM-fiberv 标本的融合率为 8/9，而 CBM-particulate 两组的融合率均为 0/9。与其他组相比，DBM-fiber 组的 μ-CT 成熟度等级明显更高（2.78±0.55）（p<0.0001），而定性评估中没有任何 CBM-particulate 样本显示横突间融合。每个 CBM 组中的活细胞和失活细胞在融合率、骨体积分数、μ-CT 成熟度等级和组织学特征方面具有可比性。
两种市售 CBMs 的细胞成分在脊柱融合方面没有带来额外的益处。同时，具有纤维状 DBM 的组与具有颗粒状 DBM 的 CBM 组相比，融合结果明显更高，表明 DBM 成分可能是融合的关键决定因素。
当前研究的数据表明，细胞在脊柱融合中没有带来额外的益处，并强调需要对细胞移植物材料进行精心设计的临床研究。
