Tissue engineering and regenerative medicine has been providing exciting technologies for the development of functional substitutes aimed to repair and regenerate damaged tissues and organs. Inspired by the hierarchical nature of bone, nanostructured biomaterials are gaining a singular attention for tissue engineering, owing their ability to promote cell adhesion and proliferation, and hence new bone growth, compared with conventional microsized materials. Of particular interest are nanocomposites involving biopolymeric matrices and bioactive nanosized fillers. Biodegradability, high mechanical strength, and osteointegration and formation of ligamentous tissue are properties required for such materials. Biopolymers are advantageous due to their similarities with extracellular matrices, specific degradation rates, and good biological performance. By its turn, calcium phosphates possess favorable osteoconductivity, resorbability, and biocompatibility. Herein, an overview on the available natural polymer/calcium phosphate nanocomposite materials, their design, and properties is presented. Scaffolds, hydrogels, and fibers as biomimetic strategies for tissue engineering, and processing methodologies are described. The specific biological properties of the nanocomposites, as well as their interaction with cells, including the use of bioactive molecules, are highlighted. Nanocomposites in vivo studies using animal models are also reviewed and discussed.

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Natural-based nanocomposites for bone tissue engineering and regenerative medicine: a review.

Bone morphogenetic protein-2 (BMP-2) is currently the only Food and Drug Administration (FDA)-approved osteoinductive growth factor used as a bone graft substitute. However, with increasing clinical use of BMP-2, a growing and well-documented side effect profile has emerged. This includes postoperative inflammation and associated adverse effects, ectopic bone formation, osteoclast-mediated bone resorption, and inappropriate adipogenesis. Several large-scale studies have confirmed the relative frequency of adverse events associated with the clinical use of BMP-2, including life-threatening cervical spine swelling. In fact, the FDA has issued a warning of the potential life-threatening complications of BMP-2. This review summarizes the known adverse effects of BMP-2, including controversial areas such as tumorigenesis. Next, select animal models that replicate BMP-2's adverse clinical effects are discussed. Finally, potential molecules to mitigate the adverse effects of BMP-2 are reviewed. In summary, BMP-2 is a potent osteoinductive cytokine that has indeed revolutionized the bone graft substitute market; however, it simultaneously has accrued a worrisome side effect profile. Better understanding of these adverse effects among both translational scientists and clinicians will help determine the most appropriate and safe use of BMP-2 in the clinical setting.

A Review of the Clinical Side Effects of Bone Morphogenetic Protein-2

Background and purpose: The appropriate fixation method for
hemiarthroplasty of the hip as it relates to implant survivorship and patient mortality is a matter of ongoing debate. We examined the influence of fixation method on revision rate and mortality.----- -----
Methods: We analyzed approximately 25,000 hemiarthroplasty
cases from the AOA National Joint Replacement Registry. Deaths at 1 day, 1 week, 1 month, and 1 year were compared for all patients and among subgroups based on implant type.----- -----
Results: Patients treated with cemented monoblock hemiarthroplasty had a 1.7-times higher day-1 mortality compared to uncemented monoblock components (p < 0.001). This finding was reversed by 1 week, 1 month, and 1 year after surgery (p < 0.001). Modular hemiarthroplasties did not reveal a difference in mortality between fixation methods at any time point.----- -----
Interpretation: This study shows lower (or similar) overall
mortality with cemented hemiarthroplasty of the hip.

Perioperative mortality after hemiarthroplasty related to fixation method : a study based on the Australian Orthopaedic Association National Joint Replacement Registry

Osteoinduction of bone grafting materials for bone repair and regeneration.

Integrins as linker proteins between osteoblasts and bone replacing materials. A critical review.

Replacement of extensive local bone loss is a significant clinical challenge. There are a variety of techniques available to the surgeon to manage this problem, each with their own advantages and disadvantages. It is well known that there is morbidity associated with harvesting of autogenous bone graft and limitations in the quantity of bone available. Alternatively allografts have been reported to have a significant incidence of postoperative infection and fracture as well as the potential risk of disease transmission. During the past 30 years a variety of synthetic bone graft substitutes has been developed with the aim to minimize these complications. The benefits of synthetic grafts include availability, sterility and reduced morbidity. The present article examines the relevance of synthetic bone graft substitutes, their mechanical properties and clinical application.

Synthetic bone graft substitutes.

Background In Australia the most frequently employed hemiarthroplasty prosthesis for the management of displaced intracapsular femoral neck fractures is the Uncemented Austin Moore (UAM). Despite concerns regarding poor functional outcomes and increased early revision rates associated with the UAM prosthesis, apprehension regarding the systemic side effects of polymethylmethacrylate cement implantation in the elderly patient continues to influence prosthesis selection. This study examines the incidence of early prosthesis related complications after UAM and Cemented Thompson (CT) hemiarthroplasty procedures for the management of femoral neck fractures. Methods A multicentre retrospective review of charts and radiographs was conducted in order to determine early prosthetic complications associated with the CT and UAM prostheses over a 6 year period in five Queensland public hospitals. Results Intraoperative periprosthetic fractures were sustained in 11.8% of UAM and 1.8% of CT implantations (p<0.0001). Intraoperative periprosthetic fractures were associated with an increased requirement for reoperation within 1 month of the index procedure (p=0.05). No statistical difference in the incidence of intraoperative periprosthetic fractures could be observed between the hospitals participating, regardless of the proportional use of each prosthesis. Early dislocation rates were similar for the UAM and CT prostheses. The intraoperative mortality rate attributable to the use of polymethylmethacrylate cement during hip hemiarthroplasty was 1/ 738 (0.14%). Conclusions The results of this study support the use of the CT prosthesis for the management of femoral neck fractures to reduce the high incidence of intraoperative periprosthetic fractures and associated requirements for early reoperation experienced with the UAM.

Early prosthetic complications after unipolar hemiarthroplasty

Background
In Australia the most frequently employed hemiarthroplasty prosthesis for the management of displaced intracapsular femoral neck fractures is the Uncemented Austin Moore (UAM). Despite concerns regarding poor functional outcomes and increased early revision rates associated with the UAM prosthesis, apprehension regarding the systemic side effects of polymethylmethacrylate cement implantation in the elderly patient continues to influence prosthesis selection. This study examines the incidence of early prosthesis related complications after UAM and Cemented Thompson (CT) hemiarthroplasty procedures for the management of femoral neck fractures.

Methods
A multicentre retrospective review of charts and radiographs was conducted in order to determine early prosthetic complications associated with the CT and UAM prostheses over a 6 year period in five Queensland public hospitals.

Results
Intraoperative periprosthetic fractures were sustained in 11.8% of UAM and 1.8% of CT implantations (p<0.0001). Intraoperative periprosthetic fractures were associated with an increased requirement for reoperation within 1 month of the index procedure (p=0.05). No statistical difference in the incidence of intraoperative periprosthetic fractures could be observed between the hospitals participating, regardless of the proportional use of each prosthesis. Early dislocation rates were similar for the UAM and CT prostheses. The intraoperative mortality rate attributable to the use of polymethylmethacrylate cement during hip hemiarthroplasty was 1/ 738 (0.14%). 

Conclusions 
The results of this study support the use of the CT prosthesis for the management of femoral neck fractures to reduce the high incidence of intraoperative periprosthetic fractures and associated requirements for early reoperation experienced with the UAM.

Early Prosthetic Complications After Unipolar Hemiarthroplasty

Introduction & Aims
For displaced intracapsular fractures of the femoral neck the most frequently employed hemiarthroplasty in Australia is the Uncemented Austin Moore (UAM) prosthesis.
Despite concerns regarding the poor functional outcome and increased revision rates associated with the UAM prosthesis, apprehension about the systemic effects of PMMA acrylic cement implantation in the elderly patient continues to influence prosthesis selection.
This study examines the incidence early prosthesis related complications after Uncemented Austin Moore (UAM) and Cemented Thompson (CT) hemiarthroplasty implantation for the management of femoral neck fractures.

William R. Moore

Papers

Synthetic bone graft substitutes.

Early prosthetic complications after unipolar hemiarthroplasty

Early Prosthetic Complications After Unipolar Hemiarthroplasty

Early Prosthetic Complications After Uncemented Austin Moore and Cemented Thompson Hemiarthroplasty. A Multicentre Review of 1118 Patients