Martin Lind

Transforming growth factor-β enhances fracture healing in rabbit tibiae

The ability of exogenous Transforming Growth Fac- densitometry. Increased maximal bending strength tor4 (TGF-D) to stimulate bone formation in fracture and callus formation were demonstrated in the healing was investigated. TGF-O was continuously groups receiving TGF-O. TGF-D had no effect on applied in doses of 1 and 10 pg/day for 6 weeks to 2 bending-stiffness, bone mineral content, cortical groups of adult rabbits with unilateral plated midtibial thickness or haversian canal diameter. We conclude osteotomies. A group receiving solvent without TGF- that local application of exogenous TGF-O may O served as control. Fracture healing was evaluated enhance fracture healing in rabbits. by mechanical tests, bone morphometry and bone

Effect of dynamic 3-D culture on proliferation, distribution, and osteogenic differentiation of human mesenchymal stem cells†

Ex vivo engineering of autologous bone tissue as an alternative to bone grafting is a major clinical need. In the present study, we evaluated the effect of 3-D dynamic spinner flask culture on the proliferation, distribution, and differentiation of human mesenchymal stem cells (MSCs). Immortalized human MSCs were cultured on porous 75:25 PLGA scaffolds for up to 3 weeks. Dynamically cultured cell/scaffold constructs demonstrated a 20% increase in DNA content (21 days), enhanced ALP specific activity (7 days and 21 days), a more than tenfold higher Ca2+ content (21 days), and significantly increased transcript levels of early osteogenesis markers (e.g., COL1A1, BMP2, RUNX-2) as compared with static culture. Despite the formation of a dense superficial cell layer, markedly increased cell ingrowth was observed by fluorescence microscopy on day 21. Furthermore, increased extracellular matrix deposition was visualized by scanning electron microscopy after 1 and 3 weeks of dynamic culture. The observed increased ingrowth and osteogenic differentiation of 3-D dynamically cultured human MSCs can be explained by generation of fluid shear stress and enhanced mass transport to the interior of the scaffold mimicking the native microenvironment of bone cells. This study provides evidence for the effectiveness of dynamic culture of human MSCs during the initial phase of ex vivo osteogenesis.

Anterior lumbar interbody fusion with carbon fiber cage loaded with bioceramics and platelet-rich plasma. An experimental study on pigs.

Platelet-rich plasma (PRP) is an autogenous source of growth factor and has been shown to enhance bone healing both in clinical and experimental studies. PRP in combination with porous hydroxyapatite has been shown to increase the bone ingrowth in a bone chamber rat model. The present study investigated whether the combination of beta tricalcium phosphate (β-TCP) and PRP may enhance spinal fusion in a controlled animal study. Ten Danish Landrace pigs were used as a spinal fusion model. Immediately prior to the surgery, 55xa0ml blood was collected from each pig for processing PRP. Three-level anterior lumbar interbody fusion was performed with carbon fiber cages and staples on each pig. Autogenous bone graft, β-TCP, and β-TCP loaded with PRP were randomly assigned to each level. Pigs were killed at the end of the third month. Fusion was evaluated by radiographs, CT scanning, and histomorphometric analysis. All ten pigs survived the surgery. Platelet concentration increased 4.4-fold after processing. Radiograph examination showed 70% (7/10) fusion rate in the autograft level. All the levels with β-TCP+PRP showed partial fusion, while β-TCP alone levels had six partial fusions and four non-fusions (P=0.08). CT evaluation of fusion rate demonstrated fusion in 50% (5/10) of the autograft levels. Only partial fusion was seen at β-TCP levels and β-TCP+PRP levels. Histomorphometric evaluation found no difference between β-TCP and β-TCP+PRP levels on new bone volume, remaining β-TCP particles, and bone marrow and fibrous tissue volume, while the same parameters differ significantly when compared with autogenous bone graft levels. We concluded from our results in pigs that the PRP of the concentration we used did not improve the bone-forming capacity of β-TCP biomaterial in anterior spine fusion. Both β-TCP and β-TCP+PRP had poorer radiological and histological outcomes than that of autograft after 3xa0months.

Can GPS Be Used to Detect Deleterious Progression in Training Volume Among Runners

Abstract Nielsen, RO, Cederholm, P, Buist, I, Sørensen, H, Lind, M, and Rasmussen, S. Can GPS be used to detect deleterious progression in training volume among runners? J Strength Cond Res 27(6): 1471–1478, 2013—There is a need to ascertain if an association exists between excessive progression in weekly volume and development of running-related injuries (RRI). The purpose of this study was to investigate if GPS can be used to detect deleterious progression in weekly training volume among 60 novice runners included in a 10-week prospective study. All participants used GPS to quantify training volume while running. In case of injury, participants attended a clinical examination. The 13 runners who sustained injuries during follow-up had a significantly higher weekly progression in total training volume in the week before the injury origin (86% [95% confidence interval: 12.9–159.9], p = 0.026) compared with other weeks. Although not significant, participants with injuries had an increase in weekly training volume of 31.6% compared with a 22.1% increase among the healthy participants. The error of the GPS measurements in open landscape, forest, and urban area of volume was ⩽6.2%. To conclude, no clinically relevant measurement errors of the GPS devices were found for training volume. Based on this, GPS has a potential to detect errors in training volume, which may be associated with development of RRI. Based on the results from the current study, increases in weekly training progression may become deleterious at a weekly increase above 30%, which is more than the 10% rule currently used as a guideline for correct progression in weekly volume by runners and coaches. Still, no clear evidence for safe progression of weekly volume exists. But it seems likely that some individuals may tolerate weekly progressions around 20–25%, at least for a short period of time.

Superficial Medial Collateral Ligament Anatomic Augmented Repair Versus Anatomic Reconstruction: An In Vitro Biomechanical Analysis

Background: When surgical intervention is required for a grade 3 superficial medial collateral ligament (sMCL) tear, there is no consensus on the optimal surgical treatment. Anatomic augmented repairs and anatomic reconstructions for treatment of grade 3 sMCL tears have not been biomechanically validated or compared. Hypothesis: Anatomic sMCL augmented repairs and anatomic sMCL reconstruction techniques will reproduce equivalent knee kinematics when compared with the intact state, while creating significant improvements in translational and rotational laxity compared with the sMCL sectioned state. Study Design: Controlled laboratory study. Methods: Eighteen match-paired, fresh-frozen cadaveric knees (average age, 52.6 years; range, 40-59 years) were each used to test laxity of an intact sMCL, a deficient sMCL, and either an anatomic augmented repair or an anatomic reconstruction. Knees were biomechanically tested in a 6 degrees of freedom robotic system, which included valgus rotation, internal and external rotation, simulated pivot shift, and coupled anterior drawer with external rotation. Results: Anatomic augmented repairs and anatomic reconstructions had significantly less medial joint gapping than the sectioned state at all tested flexion angles and showed significant reductions in valgus rotation compared with the sectioned state at all flexion angles. No significant differences between the anatomic augmented repair and anatomic reconstruction were found for any test performed. Despite the similar behavior between the 2 reconstruction groups, neither technique was able to reproduce the intact state. Conclusion: Anatomic sMCL augmented repairs and anatomic sMCL reconstructions were not significantly different when tested at time zero. Both the anatomic augmented repair and the anatomic reconstruction were able to improve knee stability and provide less than 2 mm of medial joint gapping at 0° and 20° of flexion. Clinical Significance: These results suggest that both an anatomic sMCL augmented repair and an anatomic sMCL reconstruction improve knee kinematics compared with a deficient sMCL and provide equivalent joint stability.

Effect of local prostaglandin E2 on periosteum and muscle in rabbits.

We assessed the target tissue for the stimulatory effect of prostaglandin E2 (PGE2) on bone formation previously observed during fracture healing. PGE2 was infused into tibial periosteal tissue in the right leg of 7 rabbits and into the anterior tibial muscle in the right leg of 7 other rabbits for 6 weeks. Solvent solution was infused into the left leg. PGE2 infusion at the periosteum caused the formation of primitive woven bone with large amounts of connective tissue; solvent infusion caused small amounts of normal periosteal bone formation. In the neighboring cortical bone, remodeling was increased after PGE2 infusion compared to solvent infusion. In the muscle, PGE2 infusion caused the formation of connective tissue with small amounts of woven bone. Thus, the major effects of PGE2 infusion at the site of the periosteum was the formation of primitive woven bone and in muscles the formation of connective tissue.

KNEES-ACL has superior responsiveness compared to the most commonly used patient-reported outcome measures for anterior cruciate ligament injury

PurposeFor clinical trials, it is essential that measures are sensitive to change. The aim of this study was to conductxa0a head-to-head comparison of responsiveness of four PROMs used to measure outcome after anterior cruciate ligament (ACL) reconstruction. The PROMs comparedxa0were the knee injury osteoarthritis outcome score (KOOS), the international knee documentation committee subjective form (IKDC), the Lysholm score, and the knee numeric-entity evaluation score (KNEES-ACL). We hypothesized that KNEES-ACL would be more responsive than the other PROMs, as KNEES-ACL was created based on patient interviews and validated using Rasch analysis.MethodsOne-hundred and sixty-six consecutive adults completed the four PROMs before and 3, 6, and 12 months after ACL-reconstructive surgery. Responsiveness was calculated as Cohen’s Effect Size and Standardized Response Means. Bootstrapping was used to generate 95% confidence intervals for comparisons of responsiveness across PROMs. Repeated-measures ANOVA was also computed for each PROM.ResultsThe largest effect sizes at 12 months were seen for KNEES-ACLSports-Behaviour (1.35, pu2009<u20090.001) and KNEES-ACLSports-Physical (1.19, pu2009<u20090.001), the smallest for KOOSADL (0.35, pu2009<u20090.001) and KOOSSymptoms (0.39, pu2009<u20090.001). IKDC and Lysholm lay between these with IKDC slightly more responsive. Head-to-head comparisons of similar subscales of KOOS and KNEES-ACL showed substantial differences in effect size in the domains of symptoms (0.69, pu2009<u20090.001), daily activities (0.31, pu2009=u20090.005), and Sports activity (0.63, pu2009=u20090.013) all in favour of KNEES-ACL.ConclusionThese results demonstrate superior responsiveness for KNEES-ACL, which is the only PROM that has been constructed through exhaustive patient feedback and validated for patients with ACL deficiency using the most stringent psychometric methods (Rasch analysis). KNEES-ACL is the most precise and accurate PROM for patients with ACL injury and the most trustworthy instrument for clinicians and clinical researchers.Level of evidenceProspective cohort study, Level II.

Comment to Pecina et al.

I thank Pecina and co-authors for the pertinent comments on gene therapy in cartilage repair in relation to my review paper. Their considerations and in-depth comments to aspects of gene enhanced tissue engineering in cartilage repair is highly relevant and represents the focus of comment on cartilage repair research. I could not provide such in-depth coverage to the subject in my paper due to strict limitations on the length of the paper.