Chakkalakal D A, Strates B S, Mashoof A A, Garvin K L, Novak J R, Fritz E D, Mollner T J, McGuire M H
Orthopedic Research Laboratory, VA Medical Center, Omaha, NE 68105, USA.
Bone. 1999 Sep;25(3):321-32. doi: 10.1016/s8756-3282(99)00167-2.
Bone repair models in animals may be considered relevant to human fracture healing to the extent that the sequence of events in the repair process in the model reflect the human fracture healing sequence. In the present study, the relevance of a recently developed segmental defect model in rat fibula to human fracture healing was investigated by evaluating temporal progression of rigidity of the fibula, mineral content of the repair site, and histological changes. In this model, a surgically created 2-mm-long defect was grafted with a 5-mm-long tubular specimen of demineralized bone matrix (DBM) by inserting it over the cut ends of the fibula. The temporal increase in rigidity of the healing fibula demonstrated a pattern similar to biomechanical healing curves measured in human fracture healing. This pattern was characterized by a short phase of rapidly rising rigidity during weeks 4-7 after surgery, associated with a sharp increase in the mineral content of the repair tissue. This was preceded by a phase of nearly zero rigidity and followed by a phase of slow rate of increase approaching a plateau. Histologically, chondroblastic and osteoblastic blastema originating from extraskeletal and subperiosteal (near fibula-graft junction) regions, infiltrated the DBM graft during the first 2 weeks. The DBM graft assumed the role of a "bridging callus." By weeks 6-8, most of the DBM was converted to new woven and trabecular bone with maximal osteoblastic activity and minimal endochondral ossification. Medullary callus formation started with direct new bone formation adjacent to the cortical and endosteal surfaces in the defect and undifferentiated cells in the center of the defect at 3 weeks. The usual bone repair process in rodents was altered by the presence of the DBM graft to recapitulate the sequential stages of human fracture healing, including the formation of a medullary callus, union with woven and lamellar bone, and recreation of the medullary canal.
动物的骨修复模型在其修复过程中的事件序列反映人类骨折愈合序列的程度上，可被认为与人类骨折愈合相关。在本研究中，通过评估腓骨的硬度随时间的变化、修复部位的矿物质含量以及组织学变化，研究了最近开发的大鼠腓骨节段性缺损模型与人类骨折愈合的相关性。在该模型中，通过将一个5毫米长的脱矿骨基质（DBM）管状标本插入腓骨的断端，对手术造成的2毫米长的缺损进行移植。愈合腓骨硬度随时间的增加呈现出一种模式，类似于在人类骨折愈合中测量到的生物力学愈合曲线。这种模式的特点是在手术后第4至7周有一个硬度快速上升的短阶段，与修复组织矿物质含量的急剧增加相关。在此之前是一个硬度几乎为零的阶段，之后是一个增加速率缓慢并接近平台期的阶段。组织学上，起源于骨骼外和骨膜下（靠近腓骨-移植物交界处）区域的成软骨和成骨胚基在最初2周内浸润DBM移植物。DBM移植物起到了“桥接骨痂”的作用。到第6至8周，大部分DBM转化为新的编织骨和小梁骨，成骨活性最大，软骨内成骨最少。髓内骨痂形成始于3周时在缺损处皮质和骨内膜表面附近直接形成新骨以及缺损中心的未分化细胞。啮齿动物通常的骨修复过程因DBM移植物的存在而改变，以重现人类骨折愈合的连续阶段，包括髓内骨痂的形成、与编织骨和板层骨的愈合以及髓腔的重建。
