The effect of mechanical stability on local vascularization and tissue differentiation in callus healing

Claes, Lutz; Eckert-Hübner, Kerstin; Augat, Peter

doi:10.1016/s0736-0266(02)00044-x

Cited by 239 publications

(162 citation statements)

References 12 publications

Supporting

Mentioning

141

Contrasting

Unclassified

Order By: Relevance

“…The presence of lamellar bone at right angles or perpendicular to the long axis of the bone implies a point of structural weakness not fully strengthened until remodelling the osteons of repair bone along the longitudinal axis (Olerud and Danckwardt-Lilliestrom, 1968;Perren et al, 1969;Schenk and Willenegger, 1967;Shapiro, 1988). Studies of bone defect models in stable environments help to identify the specific effects on repair of the size and stability of the gap (Claes et al, 1997;Perren, 1979) and the effects of mechanical stability on repair bone vascularity (Claes et al, 2002).…”

Section: Direct Bone Repair (Circular Defect)mentioning

confidence: 99%

Bone development and its relation to fracture repair. The role of mesenchymal osteoblasts and surface osteoblasts

Shapiro

2008

eCM

425

345

View full text Add to dashboard Cite

Bone development occurs by two mechanisms: intramembranous bone formation and endochondral bone formation. Bone tissue forms by eventual differentiation of osteoprogenitor cells into either mesenchymal osteoblasts (MOBL), which synthesize woven bone in random orientation, or surface osteoblasts (SOBL), which synthesize bone on surfaces in a well oriented lamellar array. Bone repair uses the same formation patterns as bone development but the specific mechanism of repair is determined by the biomechanical environment provided. Bone synthesis and maintenance are highly dependent on the blood supply of bone and on cell-cell communication via the lacunar-canalicular system. Recent investigations highlight the molecular cascades leading to cell differentiation, the components of the structural proteins such as the various collagens, and tissue vascularization. The patterning of bone matrix from an initial woven to an eventual lamellar orientation is essential for bone to develop its maximum strength. This review demonstrates the repetitive nature of woven to lamellar bone formation as mediated by MOBLs and SOBLs in both normal vertebrate bones and bone repair. Repair, using endochondral, primary, direct and distraction osteogenesis mechanisms, is reviewed along with the associated molecular, vascular, and biophysical features. Introductory concepts and terms Bone formationBone formation is complex but the three-dimensional positioning of cells and matrices is straightforward. As in any discussion of bone formation it is important to keep in mind the distinction between bone as a tissue (bone cells and the mineralized matrix) and bone as an organ (including several tissues such as bone, cartilage, fibrous tissue, marrow and blood vessels). Normal bone develops using only 2 mechanisms: a) Intramembranous bone formation is mediated by the inner periosteal osteogenic layer with bone synthesized initially without the mediation of a cartilage phase. b) Endochondral bone formation describes the synthesis of bone on a mineralized cartilage scaffold after epiphyseal and physeal cartilage have shaped and elongated the developing organ. These mechanisms are also used in fracture and osteotomy repair with the specific mechanism dependent on the mechanical environment provided during repair. With intramembranous bone repair, mesenchymal cells differentiate along a preosteoblast to osteoblast line while endochondral bone repair is characterized by the initial synthesis of cartilage followed by the endochondral sequence of bone formation. The terms intramembranous and endochondral refer to the tissue being replaced, not to the eventual bone synthesized which is the same in both mechanisms. Matrix orientationIn bone tissue formation osteoblasts synthesize and deposit type I collagen, the main protein constituent of bone matrix, in only 2 basic conformations, a) woven and b) lamellar. In woven bone the collagen fibrils are randomly oriented while in lamellar bone they are clustered in parallel arrays. The fibrils in lamellar...

show abstract

Section: Direct Bone Repair (Circular Defect)mentioning

confidence: 99%

Bone development and its relation to fracture repair. The role of mesenchymal osteoblasts and surface osteoblasts

Shapiro

2008

eCM

425

345

View full text Add to dashboard Cite

show abstract

“…A stable environment has long been thought to favor the formation of an intact vascular network (Claes et al, 2002;Glowacki, 1998), and this oxygen-rich environment appears to support the differentiation of skeletal progenitor cells into osteoblasts. One possibility is that a vascular network fails to form around the Mmp9 -/-stabilized fracture or the Mmp9 -/-implant site (Fig.…”

Section: Mmp9 Mediates An Angiogenic Switch During Bone Regenerationmentioning

confidence: 99%

Altered fracture repair in the absence of MMP9

et al. 2003

View full text Add to dashboard Cite

Non-stabilized and stabilized fracturesMmp9 -/-mice [3-to 5-month old; 30-35 grams (g)] and their wildtype littermates were anesthetized with an intraperitoneal injection of 2% Avertin (0.015 ml/g body weight). Closed, standardized non- The regeneration of adult skeletal tissues requires the timely recruitment of skeletal progenitor cells to an injury site, the differentiation of these cells into bone or cartilage, and the re-establishment of a vascular network to maintain cell viability. Disturbances in any of these cellular events can have a detrimental effect on the process of skeletal repair. Although fracture repair has been compared with fetal skeletal development, the extent to which the reparative process actually recapitulates the fetal program remains uncertain. Here, we provide the first genetic evidence that matrix metalloproteinase 9 (MMP9) regulates crucial events during adult fracture repair. We demonstrate that MMP9 mediates vascular invasion of the hypertrophic cartilage callus, and that Mmp9 -/-mice have non-unions and delayed unions of their fractures caused by persistent cartilage at the injury site. This MMP9-dependent delay in skeletal healing is not due to a lack of vascular endothelial growth factor (VEGF) or VEGF receptor expression, but may instead be due to the lack of VEGF bioavailability in the mutant because recombinant VEGF can rescue Mmp9 -/-non-unions. We also found that Mmp9 -/-mice generate a large cartilage callus even when fractured bones are stabilized, which implicates MMP9 in the regulation of chondrogenic and osteogenic cell differentiation during early stages of repair. In conclusion, the resemblance between Mmp9 -/-fetal skeletal defects and those that emerge during Mmp9 -/-adult repair offer the strongest evidence to date that similar mechanisms are employed to achieve bone formation, regardless of age.

show abstract

“…17 Structural stability is considered as a crucial factor for bone healing. 45,46 Biomechanical studies have already suggested that plate fixation provides significant structural stability in itself, 47 and through this stability, the normal process of fracture healing continues without restrictions. Therefore, it is questionable whether bone grafts are needed for structural stability.…”

Section: Discussionmentioning

confidence: 99%

Is Bone Grafting Necessary in the Treatment of Malunited Distal Radius Fractures?

et al. 2015

View full text Add to dashboard Cite

Background?Open wedge osteotomy with bone grafting and plate fixation is the standard procedure for the correction of malunited distal radius fractures. Bone grafts are used to increase structural stability and to enhance new bone formation. However, bone grafts are also associated with donor site morbidity, delayed union at bone?graft interfaces, size mismatch between graft and osteotomy defect, and additional operation time. Purpose?The goal of this study was to assess bone healing and secondary fracture displacement in the treatment of malunited distal radius fractures without the use of bone grafting. Methods?Between January 1993 and December 2013, 132 corrective osteotomies and plate fixations without bone grafting were performed for malunited distal radius fractures. The minimum follow-up time was 12 months. Primary study outcomes were time to complete bone healing and secondary fracture displacement. Preoperative and postoperative radiographs during follow-up were compared with each other, as well as with radiographs of the uninjured side. Results?All 132 osteotomies healed. In two cases (1.5%), healing took more than 4 months, but reinterventions were not necessary. No cases of secondary fracture displacement or hardware failure were observed. Significant improvements in all radiographic parameters were shown after corrective osteotomy and plate fixation. Conclusion?This study shows that bone grafts are not required for bone healing and prevention of secondary fracture displacement after corrective osteotomy and plate fixation of malunited distal radius fractures. Level of evidence?Therapeutic, level IV, case series with no comparison group

show abstract

The effect of mechanical stability on local vascularization and tissue differentiation in callus healing

Cited by 239 publications

References 12 publications

Bone development and its relation to fracture repair. The role of mesenchymal osteoblasts and surface osteoblasts

Bone development and its relation to fracture repair. The role of mesenchymal osteoblasts and surface osteoblasts

Altered fracture repair in the absence of MMP9

Is Bone Grafting Necessary in the Treatment of Malunited Distal Radius Fractures?

Contact Info

Product

Resources

About