Novel microhydroxyapatite particles in a collagen scaffold: a bioactive bone void filler?

BACKGROUND: Treatment of segmental bone loss remains a major challenge in orthopaedic surgery. Traditional techniques (eg, autograft) and newer techniques (eg, recombinant human bone morphogenetic protein-2 [rhBMP-2]) have well-established performance limitations and safety concerns respectively. Consequently there is an unmet need for osteoinductive bone graft substitutes that may eliminate or reduce the use of rhBMP-2. QUESTIONS/PURPOSES: Using an established rabbit radius osteotomy defect model with positive (autogenous bone graft) and negative (empty sham) control groups, we asked: (1) whether a collagen-glycosaminoglycan scaffold alone can heal the defect, (2) whether the addition of hydroxyapatite particles to the collagen scaffold promote faster healing, and (3) whether the collagen-glycosaminoglycan and collagen-hydroxyapatite scaffolds are able to promote faster healing (by carrying a low dose rhBMP-2). METHODS: A 15-mm transosseous radius defect in 4-month-old skeletally mature New Zealand White rabbits were treated with either collagen-hydroxyapatite or collagen-glycosaminoglycan scaffolds with and without rhBMP-2. Autogenous bone graft served as a positive control. Time-series radiographs at four intervals and postmortem micro-CT and histological analysis at 16 weeks were performed. Qualitative histological analysis of postmortem explants, and qualitative and volumetric 3-D analysis of standard radiographs and micro-CT scans enabled direct comparison of healing between test groups. RESULTS: Six weeks after implantation the collagen-glycosaminoglycan group had callus occupying greater than ½ the defect, whereas the sham (empty) control defect was still empty and the autogenous bone graft defect was completely filled with unremodeled bone. At 6 weeks, the collagen-hydroxyapatite scaffold groups showed greater defect filling with dense callus compared with the collagen-glycosaminoglycan controls. At 16 weeks, the autogenous bone graft groups showed evidence of early-stage medullary canal formation beginning at the proximal and distal defect borders. The collagen-glycosaminoglycan and collagen-glycosaminoglycan-rhBMP-2 groups had nearly complete medullary canal formation and anatomic healing at 16 weeks. However, collagen-hydroxyapatite-rhBMP-2 scaffolds showed the best levels of healing, exhibiting a dense callus which completely filled the defect. CONCLUSIONS: The collagen-hydroxyapatite scaffold showed comparable healing to the current gold standard of autogenous bone graft. It also performed comparably to collagen-glycosaminoglycan-rhBMP-2, a representative commercial device in current clinical use, but without the cost and safety concerns. CLINICAL RELEVANCE: The collagen-glycosaminoglycan scaffold may be suitable for a low load-bearing defect. The collagen-hydroxyapatite scaffold may be suitable for a load-bearing defect. The rhBMP-2 containing collagen-glycosaminoglycan and collagen-hydroxyapatite scaffolds may be suitable for established nonunion defects.

A guide to preprinting for early-career researchers.

The use of preprints, research manuscripts shared publicly before completing the traditional peer-review process, is becoming a more common practice among life science researchers. Early-career researchers (ECRs) benefit from posting preprints as they are shareable, citable, and prove productivity. However, preprinting a manuscript involves a discussion among all co-authors, and ECRs are often not the decision-makers. Therefore, ECRs may find themselves in situations where they are interested in depositing a preprint but are unsure how to approach their co-authors or advisor about preprinting. Leveraging our own experiences as ECRs, and feedback from the research community, we have constructed a guide for ECRs who are considering preprinting to enable them to take ownership over the process and to raise awareness about preprinting options. We hope that this guide helps ECRs to initiate conversations about preprinting with co-authors and encourage them to preprint their future research.

The effect of physiological cyclic stretch on the cell morphology, cell orientation and protein expression of endothelial cells.

In vivo, endothelial cells are constantly exposed to pulsatile shear and tensile stresses. The main aim of this study was to design and build a physiological simulator, which reproduced homogenous strain profiles of the tensile strain experienced in vivo, and to investigate the effect of this cyclic tensile strain on the cell morphology, cell orientation and protein expression of endothelial cells. The biological response of human umbilical vein endothelial cells to a uniaxial cyclic stretch, in this newly developed simulator, was examined experimentally using immunohistostaining and confocal imaging and it was found that the cells elongated and oriented at 58.9 degrees +/- 4.5 degrees . This value was compared to a mathematical model where it was revealed that endothelial cells would orient at an angle of 60 degrees . This model also revealed that endothelial cells have an axial strain threshold value of 1.8% when exposed to a 10% cyclic strain at 1 Hz for 3 h. Cells cultured under conditions of cyclic strain showed increased ICAM-1 immunostaining when compared to static cells whereas, a marked decrease in the levels of VCAM-1 receptor staining was also observed. Haemodynamic stresses can modulate the endothelial cell adhesion response in vivo thus, taken together; this data validates the bioreactor as replicating the physiological environment.