The relevance of biomaterials to the prevention and treatment of osteoporosis.

The relevance of biomaterials to the prevention and treatment of osteoporosis. Opinion paper

Severe heat-shock to bone cells caused during orthopaedic procedures can result in thermal damage, leading to cell death and initiating bone resorption. By contrast, mild heat-shock has been proposed to induce bone regeneration. In this study, bone cells are exposed to heat-shock for short durations occurring during surgical cutting. Cellular viability, necrosis and apoptosis are investigated immediately after heat-shock and following recovery of 12, 24 h and 4 days, in osteocyte-like MLO-Y4 and osteoblast-like MC3T3-E1 cells, using flow cytometry. The regeneration capacity of heat-shocked Balb/c mesenchymal stem cells (MSCs) and MC3T3-E1s has been investigated following 7 and 14 day's recovery, by quantifying proliferation, differentiation and mineralization. An immediate necrotic response to heat-shock was shown in cells exposed to elevated temperatures (45°C, 47°C and most severe at 60°C). A longer-term apoptotic response is induced in MLO-Y4s and, to a lesser extent, in MC3T3-E1s. Heat-shock-induced differentiation and mineralization by MSCs. These findings indicate that heat-shock is more likely to induce apoptosis in osteocytes than osteoblasts, which might reflect their role as sensors detecting and communicating damage within bone. Furthermore, it is shown for the first time that mild heat-shock (less than equal to 47°C) for durations occurring during surgical cutting can positively enhance osseointegration by osteoprogenitors.

https://royalsocietypublishing.org/doi/pdf/10.1098/rsif.2012.0520

Heat-shock-induced cellular responses to temperature elevations occurring during orthopaedic cutting

Bone reconstruction techniques are mainly based on the use of tissue grafts and artificial scaffolds. The former presents well-known limitations, such as restricted graft availability and donor site morbidity, while the latter commonly results in poor graft integration and fixation in the bone, which leads to the unbalanced distribution of loads, impaired bone formation, increased pain perception, and risk of fracture, ultimately leading to recurrent surgeries. In the past decade, research efforts have been focused on the development of innovative bone substitutes that not only provide immediate mechanical support, but also ensure appropriate graft anchoring by, for example, promoting de novo bone tissue formation. From the countless studies that aimed in this direction, only few have made the big jump from the benchtop to the bedside, whilst most have perished along the challenging path of clinical translation. Herein, we describe some clinically successful cases of bone device development, including biological glues, stem cell-seeded scaffolds, and gene-functionalized bone substitutes. We also discuss the ventures that these technologies went through, the hindrances they faced and the common grounds among them, which might have been key for their success. The ultimate objective of this perspective article is to highlight the important aspects of the clinical translation of an innovative idea in the field of bone grafting, with the aim of commercially and clinically informing new research approaches in the sector.

/pdf/the-few-who-made-it-commercially-and-clinically-successful-2o50ilaa1g.pdf

The Few Who Made It : Commercially and Clinically Successful Innovative Bone Grafts

The concept of supporting fractured long bones externally with mechanical fixation has been evidentially applied for over 2000 years, and since been expanded on in the mid-19th century by percutaneous bone fixation. Surgical techniques, external fixator systems, and materials have made continued progress since. The benefits of traditional external fixation have been enhanced in recent years with the introduction of hexapod-style fixators, innovative configurations, and pin modifications, among other things. It is generally agreed upon that biomechanical testing of advancements in external fixation must be inclusive of transverse or torsional loading to simulate construct behaviour in realistic scenarios. Biomechanical studies indicate that hexapod-style fixators show comparable axial stiffness to Ilizarov-style systems and improved performance under torsional and transverse forces. The addition of configuration elements to fixators, inclusion of certain carbon fibre chemical compositions, and techniques intended to augment ring thickness have also been investigated, in hopes of increasing construct stiffness under loading. Novel external fixators attempt to broaden their applications by rethinking bone mounting mechanisms and either expanding on or simplifying the implementation of 3D bone segment transport for corrective osteotomy. Older and seemingly unconventional fixation techniques are being rediscovered and evolved further in order to increase patient comfort by improving everyday usability. The development of new pin coatings can potentially enhance the pin-bone interface while lowering infection rates typically expected at thicker soft tissue envelopes. Although complication, malunion, and nonunion rates have decreased over the past 50 years, the clinical results of external fixation today can still be optimized. Unsatisfactory healing in the lower extremities has especially been reported at locations such as the distal tibia; however, advancements such as osteoinductive growth hormone treatment may provide improved results. With the current progression of technology and digitization, it is only a matter of time before 'smart', partly-autonomous external fixation systems enter the market. This review article will provide a versatile overview of biomechanically proven fixator configurations and some carefully selected innovative systems and techniques that have emerged or been established in the past two decades.

External fixation of the lower extremities: Biomechanical perspective and recent innovations.

Injectable calcium phosphate cement for augmentation around cancellous bone screws. In vivo biomechanical studies.

Background External fixation has become a quick and easy application for fracture stabilisation of the extremities and/or pelvis to maintain the reduction and provide stability while sparing the soft tissues. Over the last years, enhanced construct stiffness has become an essential requirement to preserve fracture reduction, particularly in active and overweight patients. This study was performed to determine whether the advancement of design features enhances the external fixation construct stiffness. The stiffness of the recently developed Hoffmann 3 external fixation system was determined and its characteristics compared with the widely clinically accepted Hoffmann II MRI fixation system. Methods A synthetic fracture model was used. Two carbon tubes with a fracture gap of 20 mm were appropriate to determine the stiffness of three different configurations: the basic frame configuration (group H 3, representing Hoffmann 3 with a rod diameter of 11 mm) using a double rod construction with 6 mm Apex pins, was compared with the Hoffmann II MRI fixation system using two 8.0 mm diameter rods with 6 mm (group H II-6 mm) and 5 mm (group H II-5 mm) Apex pins. Each group was tested five times under anterior-posterior bending (N/mm), medio-lateral bending (N/mm) and axial torsion loading directions (Nm/deg). The stiffness results of each construct were compared statistically. Results The basic frame construct (group H 3) showed consistently higher stiffness properties compared with the other configurations. The anterior-posterior-bending loads resulted in a mean value of 31 N/mm, which was significantly higher compared with the other groups (p=0.008) at 16 N/mm. The medio-lateral-bending test revealed a mean stiffness of 59 N/mm in the H3 group, compared with 43 N/mm in the H II-6 group and 31 N/mm in the H II-5 group. The axial torsion measurements of the Hoffmann 3 group yielded significantly higher results (1.03 Nm/°) compared with group H II-6 (0.61 Nm/°) and group H II-5 (0.56 Nm/°). Conclusions The Hoffmann 3 construct showed the highest stiffness properties under bending and torsion loads. The enhanced stiffness of the Hoffmann 3 device may be helpful in maintaining fracture reduction and soft tissue compromise. This investigation showed the advancement of Hoffmann design features may be effective in enhancing frame stiffness.

External fixation design evolution enhances biomechanical frame performance.

Calcium phosphate augmentation of cancellous bone screws in impaired lapine bone

Purpose
External fixators are easy to apply and maximize soft tissue preservation. However, frames need providing an adequate stiffness in order to avoid excessive interfragmentary movement during the healing period. We characterized the stiffness of four different configurations of the newly developed Hoffmann 3 external fixation system.

Biomechanical properties of different external fixator frame configurations

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Injectable calcium phosphate cement for augmentation around cancellous bone screws. In vivo biomechanical studies.

External fixation design evolution enhances biomechanical frame performance.

Calcium phosphate augmentation of cancellous bone screws in impaired lapine bone

Biomechanical properties of different external fixator frame configurations