William Lu

Activation and promotion of adipose stem cells by tumour necrosis factor‐alpha preconditioning for bone regeneration

There is a major medical need for developing novel and effective approaches for repairing non‐union and critical‐sized bone defects. Although the mechanisms remain to be determined, it is known that inflammation plays a crucial role in initiating bone repair and regeneration. This study investigated the effect of short‐term (3 days) preconditioning with tumor necrosis factor‐alpha (TNF‐α) on proliferation, mobilization, and differentiation of adipose tissue‐derived mesenchymal stem cells (ASCs). We demonstrated that TNF‐α pre‐conditioning increased proliferation, mobilization, and osteogenic differentiation of ASCs and up‐regulated bone morphogenetic protein‐2 (BMP‐2) protein level. BMP‐2 silencing by siRNA partially inhibited osteogenic differentiation of ASCs induced by TNF‐α; BMP‐2 pre‐conditioning also significantly increased osteogenic differentiation of ASCs but the effects were significantly smaller than those observed for TNF‐α preconditioning. Furthermore, TNF‐α treatment promoted extracellular‐signal‐regulated kinases(Erk)1/2 and p38 mitogen‐activated protein kinase (MAPK) signaling pathways, but only Erk1/2 inhibition reduced the BMP‐2 levels and osteogenic differentiation induced by TNF‐α preconditioning. Together, these results support the hypothesis that inflammation contributes to bone regeneration by promoting proliferation, mobilization, and osteogenic differentiation of ASCs; 3 days of TNF‐α preconditioning, mimicking the short boost of inflammation normally occurring after bone injury, might serve as a feasible approach for directing stem cells into osteogenic differentiation. J. Cell. Physiol. 9999: XX–XX, 2013.

Single-stage osseointegrated reconstruction and rehabilitation of lower limb amputees: the Osseointegration Group of Australia Accelerated Protocol-2 (OGAAP-2) for a prospective cohort study

Introduction Lower limb amputations have detrimental influences on the quality of life, function and body image of the affected patients. Following amputation, prolonged rehabilitation is required for patients to be fitted with traditional socket prostheses, and many patients experience symptomatic socket–residuum interface problems which lead to reduced prosthetic use and quality of life. Osseointegration has recently emerged as a novel approach for the reconstruction of amputated limbs, which overcomes many of the socket-related problems by directly attaching the prosthesis to the skeletal residuum. To date, the vast majority of osseointegration procedures worldwide have been performed in 2 stages, which require at least 4 months and up to 18 months for the completion of reconstruction and rehabilitation from the time of the initial surgery. The current prospective cohort study evaluates the safety and efficacy of a single-stage osseointegration procedure performed under the Osseointegration Group of Australia Accelerated Protocol-2 (OGAAP-2), which dramatically reduces the time of recovery to ∼3–6 weeks. Methods and analysis The inclusion criteria for osseointegrated reconstruction under the OGAAP-2 procedure are age over 18 years, unilateral transfemoral amputation and experiencing problems or difficulties in using socket prostheses. All patients receive osseointegrated implants which are press-fitted into the residual bone. Functional and quality-of-life outcome measures are recorded preoperatively and at defined postoperative follow-up intervals up to 2 years. Postoperative adverse events are also recorded. The preoperative and postoperative values are compared for each outcome measure, and the benefits and harms of the single-stage OGAAP-2 procedure will be compared with the results obtained using a previously employed 2-stage procedure. Ethics and dissemination This study has received ethics approval from the University of Notre Dame, Sydney, Australia (014153S). The study outcomes will be disseminated by publications in peer-reviewed academic journals and presentations at relevant clinical and orthopaedic conferences.

Two-Stage Osseointegrated Reconstruction of Post-traumatic Unilateral Transfemoral Amputees

A new technique called osseointegration was introduced recently by intimately connecting the artificial limb prosthesis to the residual bone, eliminating the problematic socket-residuum interface. The objective here is to describe the two-stage strategy for the osseointegrated reconstruction of amputated limbs and discuss the clinical outcomes of the procedure. This is a prospective case series of 37 post-traumatic unilateral transfemoral amputees with a minimum 2-yr follow-up. Outcome measures included the Questionnaire for persons with a Transfemoral Amputation (Q-TFA), the Short Form Health Survey 36 (SF-36), the 6 Minute Walk Test (6MWT), and Timed Up and Go (TUG) tests. Adverse events including infection, revision surgery, fractures, and implant failures were reported. Clinical outcomes for all outcome measures were significantly improved at follow-up. Twelve participants were wheelchair bound pre-operatively; however, all 12 were able to ambulate after osseointegrated reconstruction. Sixteen patients experienced infection episodes but were managed successfully without the need for implant removal. One periprosthetic fracture occurred due to increased activity, which was revised successfully. These results confirm that the procedure is a suitable alternative for post-traumatic unilateral transfemoral amputees experiencing socket-related discomfort, with the potential to reduce recovery time compared with other treatment protocols.