The role of peptides in bone healing and regeneration: A systematic review

Background: Bone tissue engineering and the research surrounding peptides has expanded significantly over the last few decades. Several peptides have been shown to support and stimulate the bone healing response and have been proposed as therapeutic vehicles for clinical use. The aim of this comprehensive review is to present the clinical and experimental studies analysing the potential role of peptides for bone healing and bone regeneration. Methods: A systematic review according to PRISMA guidelines was conducted. Articles presenting peptides capable of exerting an upregulatory effect on osteoprogenitor cells and bone healing were included in the study. Results: Based on the available literature, a significant amount of experimental in vitro and in vivo evidence exists. Several peptides were found to upregulate the bone healing response in experimental models and could act as potential candidates for future clinical applications. However, from the available peptides that reached the level of clinical trials, the presented results are limited. Conclusion: Further research is desirable to shed more light into the processes governing the osteoprogenitor cellular responses. With further advances in the field of biomimetic materials and scaffolds, new treatment modalities for bone repair will emerge

Surgical Site Infection Following Intramedullary Nailing of Subtrochanteric Femoral Fractures

Aim: To investigate the incidence, risk factors and pathogenic micro-organisms causing superficial and deep infection in subtrochanteric femoral fractures managed with an intramedullary nail. Materials and Methods: Following institutional board approval, all consecutive patients presenting with a subtrochanteric fracture were retrospectively identified, over an 8-year period. Basic demographics, fracture characteristics, fracture union, revision operation, mortality and other complications were reported and analysed. Variables deemed statistically significant (p-value < 0.05) were then included into a revised adjusted model of logistic regression analysis, where we reported on the odds ratio (OR). Results: The overall incidence of infection was 6.4% (n = 36/561; superficial: 3.7%; deep: 2.7%). Associations with deep infection included: non-union (OR 9.29 (2.56–3.38)), the presence of an open fracture (OR 4.23 (3.18–5.61)), the need for massive transfusion (OR 1.42 (2.39–8.39)), post-operative transfusion (OR 1.40 (1.10–1.79)) and prolonged length of stay (OR 1.04 (1.02–1.06)). The Commonest causes of superficial infection were Staphylococcus aureus (28.5%), enteric flora (23.8%) and mixed flora (23.8%); whereas coliforms (60%) and Staphylococcus aureus (26.7%) were the commonest micro-organisms isolated in deep infection. Polymicrobial infection was identified in 38.5% and 80% of superficial and deep infections, respectively. Conclusion: Causative micro-organisms identified in both superficial and deep infection were similar to those reported in post-traumatic osteomyelitis. In an attempt to minimise infection, the treating clinician should focus on modifiable risk factors with adequate patient optimisation, prompt surgical treatment, adequate antibiotic coverage and wound care when treating patients with subtrochanteric femur fracture

Subtrochanteric fracture non-unions: development of a risk scoring system for predicting non-unions and biological characterisation of the non-union tissue

The aim of this thesis was three-fold. Firstly, to investigate the characteristics of patients presenting with subtrochanteric fractures treated with intra-medullary fixation and describe their outcomes, with a special reference to the development of non-union; secondly, to identify risk factors predisposing to non-union and to develop a scoring system that could predict the development of this complication; thirdly, to analyse the biological and molecular profile of fracture non-union tissue. Between January 2009 and December 2016 (eight years), 545 consecutive patients (561 fractures) were treated for proximal femoral fractures extending into the subtrochanteric area, fulfilling the inclusion criteria. Their management and outcomes were reported, with subgroup analysis identifying associations for developing common complications (including non-union; infection; effect of open reduction / osteoporosis / bisphosphonates; atypical fractures; type of nail used; transfusion requirements; presence of a ‘weekend effect’, medical complications and mortality). Regression analysis identified several factors associated with an increased risk non-union (deep infection; self-dynamisation; presence of an atypical fracture; diabetes; and malreduction, as demonstrated by a lateral cortex fracture gap size and varus malalignment), with another factor (moderate comminution) being associated with a decreased risk. Based on these findings, a risk scoring system for predicting non-unions was developed. Additionally, open reduction of subtrochanteric fractures was not associated with an increased risk of deep infection and non-union. The use of cerclage wiring however was found to be associated with a decreased incidence of non-union without an increase in complications. Regarding the laboratory part, following ethics committee approval, ten patients undergoing revision surgery as part of their treatment for atrophic non-union were recruited. Functional assays and gene analysis were performed on the isolated osteoprogenitor cells to elucidate their biological and molecular profile. Comparing the samples’ gene expression at baseline, three genes were found to be over-expressed in non-union tissue mesenchymal stem cells (MSCs) (ICAM1, MMP10 and GLI1), whilst another four genes were under-expressed (EGF, IGF2, MMP8 and COL14A1). Comparing non-union versus bone MSCs following osteogenic stimulation (i.e. osteoblastic differentiation), only IGF2 and EGF were significantly under-expressed in non-union MSCs

Development and Validation of a Post-Operative Non-Union Risk Score for Subtrochanteric Femur Fractures

Background: Our objective was to develop and validate a predictive model for non-union following a subtrochanteric fracture of the femur. Methods: Following institutional board approval, 316 consecutive patients presenting to our institution (84 non-unions) who fulfilled the inclusion criteria were retrospectively identified. To identify potential unadjusted associations with progression to non-union, simple logistic regression models were used, followed by a revised adjusted model of multiple logistic regression. Results: Having established the risk factors for non-union, the coefficients were used to produce a risk score for predicting non-union. To identify the high-risk patients in the early post-operative period, self-dynamisation was excluded. The revised scoring system was the sum of the following: diabetes (6); deep wound infection (35); simple or severe comminution (13); presence of an atypical fracture (14); lateral cortex gap size ≥5 mm (11), varus malreduction (5–10 degrees) (9); varus malreduction (>10 degrees) (20). On the ROC (receiver operating characteristic) curve, the area under the curve (0.790) demonstrated very good discriminatory capability of the scoring system, with good calibration (Hosmer–Lemeshow test; p = 0.291). Moreover, 5-fold cross validation confirmed good fit of the model and internal validity (accuracy 0.806; Kappa 0.416). The cut-point determined by Youden’s formula was calculated as 18. Conclusion: This study demonstrates that the risk of non-union can be reliably estimated in patients presenting with a subtrochanteric fracture, from the immediate post-operative period. The resulting non-union risk score can be used not only to identify the high-risk patients early, offering them appropriate consultation and in some cases surgical intervention, but also informs surgeons of the modifiable surgery related factors that contribute to this risk