The absence of immediate stimulation delays bone healing.

AIM: Secondary bone healing requires an adequate level of mechanical stimulation expressed by the extent of interfragmentary motion in the fracture. However, there is no consensus about when the mechanical stimulation should be initiated to ensure a timely healing response. Therefore, this study aims to compare the effect of the immediate and delayed application of mechanical stimulation in a large animal model. METHODS: Twelve Swiss White Alpine sheep underwent partial osteotomy of a tibia that was stabilised with an active fixator inducing well-controlled mechanical stimulation. Animals were randomly assigned into two groups with different stimulation protocols. The immediate group received daily stimulation (1000 cycles/day) from the first day post-operation, while in the delayed group, stimulation began only on the 22nd day post-operation. Healing progression was evaluated daily by measuring the in vivo stiffness of the repair tissue and by quantifying callus area on weekly radiographs. All animals were euthanised five weeks post-op. Post-mortem callus volume was determined from high-resolution computer tomography (HRCT). RESULTS: Fracture stiffness (p < 0.05) and callus area (p < 0.01) were significantly larger for the immediate group compared to the delayed stimulation group. In addition, the callus volume measured on the post-mortem HRCT showed 319 % greater callus volume for the immediate stimulation group (p < 0.01). CONCLUSIONS: This study demonstrates that a delay in the onset of mechanical stimulation retards fracture callus development and that mechanical stimulation already applied in the early post-op phase promotes bone healing.

Superior fixation strength of coronoid process replacement using individually designed 3D printed prosthesis with curved cemented intramedullary stem.

BACKGROUND: Coronoid fractures frequently occur as part of complex elbow injuries and account for 2%-15% of the cases with dislocations. Comminuted fractures and nonunions necessitate surgical treatment. Considering the latest technological advancements, the aim of this study was to investigate the fixation strength of coronoid replacement using an individualized 3D printed prosthesis with curved cemented intramedullary (IM) stem vs. both radial head grafted reconstruction and coronoid fixation. METHODS: Twenty-four human cadaveric paired forearms were stripped of soft tissue and their computed tomography scanned ulnas were randomized to 4 groups for coronoid replacement (prosthesis group), radial head grafted reconstruction (radial head group), fixation (fixation group), or no treatment (intact group). The ulnas in all groups, except the intact one, were osteotomized at 40% of the coronoid height and the coronoid process was either replaced with a 3D printed stainless-steel prosthesis with curved cemented IM stem individually designed based on the contralateral scan (prosthesis group), reconstructed with an ipsilateral radial head autograft fixed with 2 anteroposterior screws (radial head group), or fixed in situ with 2 anteroposterior screws (fixation group). All specimens were biomechanically tested under ramped quasistatic axial loading. RESULTS: Bone mineral density was not significantly different among the groups (P = .95). Stiffness and failure load in the prosthesis group was significantly higher compared to all other groups (P ≤ .04) and in addition, it was significantly lower in the fixation group compared to the intact group (P = .03), with no further detected significant differences among the groups (P ≥ .72). Absorbed energy to failure in the prosthesis group was significantly more compared to both radial head and fixation groups (P ≤ .04) but not vs. the intact group. Failure deformation at the osteotomy site was not significantly different among the groups (P = .26). CONCLUSIONS: Coronoid process replacement using an anatomically shaped, individually designed 3D printed prosthesis with curved cemented IM stem seems to be an effective method to restore the coronoid buttress function under axial loading. This method provides superior fixation strength over both radial head grafted reconstruction and screw fixation.

Volar versus combined dorsal and volar plate fixation of complex intraarticular distal radius fractures with small dorsoulnar fragment - a biomechanical study.

Complex intraarticular distal radius fractures (DRFs), commonly managed with volar locking plates, are challenging. Combined volar and dorsal plating is frequently applied for treatment, however, biomechanical investigations are scant. The aim of this biomechanical study was to investigate volar plating versus double plating in DRFs with different degrees of lunate facet comminution.Thirty artificial radii with simulated AO/OTA 23-C2.1 and C3.1 DRFs, including dorsal defect and lunate facet comminution, were assigned to 3 groups: Group 1 with two equally-sized lunate facet fragments; Group 2 with small dorsal and large volar fragment; Group 3 with three equally-sized fragments. The specimens underwent volar and double locked plating and non-destructive ramped loading in 0° neutral position, 40° flexion and 40° extension.In each tested position, stiffness: (1) did not significantly differ among groups with same fixation method (p ≥ 0.15); (2) increased significantly after supplemental dorsal plating in Group 2 and Group 3 (p ≤ 0.02).Interfragmentary displacements between styloid process and lunate facet in neutral position were below 0.5 mm, being not significantly different among groups and plating techniques (p ≥ 0.63).Following volar plating, angular displacement of the lunate facet to radius shaft was significantly lower in Group 1 versus both Group 2 and Group 3 (p < 0.01). It decreased significantly after supplemental dorsal plating in Group 2 and Group 3 (p < 0.01), but not in Group 1 (p ≥ 0.13), and did not differ significantly among the three groups after double plating (p ≥ 0.74).Comminution of the lunate facet within its dorsal third significantly affected the biomechanical outcomes related to complex intraarticular DRFs treated with volar and double locked plates.Double plating demonstrates superior stability versus volar plating only for lunate facet comminution within its dorsal third. In contrast, volar plating could achieve stability comparable with double plating when the dorsal third of the lunate facet is not separated by the fracture pattern. Both fixation methods indicated achievable absolute stability between the articular fragments.

Short-Term Bone Healing Response to Mechanical Stimulation-A Case Series Conducted on Sheep.

It is well known that mechanical stimulation promotes indirect fracture healing by triggering callus formation. We investigated the short-term response of healing tissue to mechanical stimulation to compare the changes in tissue stiffness during stimulation and resting phases in a preclinical case-series. Four sheep underwent a tibial osteotomy and were instrumented with a custom-made active fixator which applied a mechanical stimulation protocol of 1000 cycles/day, equally distributed over 12 h, followed by 12 h of rest. During each cycle, a surrogate metric for tissue stiffness was measured, enabling a continuous real-time monitoring of the healing progression. A daily stiffness increase during stimulation and an increase during resting were evaluated for each animal. One animal had to be excluded from the evaluation due to technical reasons. For all included animals, the stiffness began to increase within the second week post-op. A characteristic pattern was observed during daily measurements: the stiffness dropped considerably within the first stimulation cycles followed by a steady rise throughout the rest of the stimulation phase. However, for all included animals, the average daily stiffness increase within the first three weeks post operation was larger during resting than during stimulation (Sheep I: 16.9% vs. -5.7%; Sheep II: 14.7% vs. -1.8%; Sheep III: 8.9% vs. 1.6%). A continuous measurement of tissue stiffness together with a controlled fracture stimulation enabled the investigation of the short-term effects of specific stimulatory parameters, such as resting periods. Resting was identified as a potentially determining factor for bone healing progression. Optimizing the ratio between stimulation and resting may contribute to more robust fracture healing in the future.

Can Optimizing the Mechanical Environment Deliver a Clinically Significant Reduction in Fracture Healing Time?

The impact of the local mechanical environment in the fracture gap on the bone healing process has been extensively investigated. Whilst it is widely accepted that mechanical stimulation is integral to callus formation and secondary bone healing, treatment strategies that aim to harness that potential are rare. In fact, the current clinical practice with an initially partial or non-weight-bearing approach appears to contradict the findings from animal experiments that early mechanical stimulation is critical. Therefore, we posed the question as to whether optimizing the mechanical environment over the course of healing can deliver a clinically significant reduction in fracture healing time. In reviewing the evidence from pre-clinical studies that investigate the influence of mechanics on bone healing, we formulate a hypothesis for the stimulation protocol which has the potential to shorten healing time. The protocol involves confining stimulation predominantly to the proliferative phase of healing and including adequate rest periods between applications of stimulation.

Programable Active Fixator System for Systematic In Vivo Investigation of Bone Healing Processes.

This manuscript introduces a programable active bone fixator system that enables systematic investigation of bone healing processes in a sheep animal model. In contrast to previous systems, this solution combines the ability to precisely control the mechanical conditions acting within a fracture with continuous monitoring of the healing progression and autonomous operation of the system throughout the experiment. The active fixator system was implemented on a double osteotomy model that shields the experimental fracture from the influence of the animal's functional loading. A force sensor was integrated into the fixator to continuously measure stiffness of the repair tissue as an indicator for healing progression. A dedicated control unit was developed that allows programing of different loading protocols which are later executed autonomously by the active fixator. To verify the feasibility of the system, it was implanted in two sheep with different loading protocols, mimicking immediate and delayed weight-bearing, respectively. The implanted devices operated according to the programmed protocols and delivered seamless data over the whole course of the experiment. The in vivo trial confirmed the feasibility of the system. Hence, it can be applied in further preclinical studies to better understand the influence of mechanical conditions on fracture healing.

Sound-induced morphogenesis of multicellular systems for rapid orchestration of vascular networks.

Morphogenesis, a complex process, ubiquitous in developmental biology and many pathologies, is based on self-patterning of cells. Spatial patterns of cells, organoids, or inorganic particles can be forced on demand using acoustic surface standing waves, such as the Faraday waves. This technology allows tuning of parameters (sound frequency, amplitude, chamber shape) under contactless, fast and mild culture conditions, for morphologically relevant tissue generation. We call this method Sound Induced Morphogenesis (SIM). In this work, we use SIM to achieve tight control over patterning of endothelial cells and mesenchymal stem cells densities within a hydrogel, with the endpoint formation of vascular structures. Here, we first parameterize our system to produce enhanced cell density gradients. Second, we allow for vasculogenesis after SIM patterning control and compare our controlled technology against state-of-the-art microfluidic culture systems, the latter characteristic of pure self-organized patterning and uniform initial density. Our sound-induced cell density patterning and subsequent vasculogenesis requires less cells than the microfluidic chamber. We advocate for the use of SIM for rapid, mild, and reproducible morphogenesis induction and further explorations in the regenerative medicine and cell therapy fields.

Does Supplemental Intramedullary Grafting Increase Stability of Plated Proximal Humerus Fractures?

OBJECTIVES: To investigate the biomechanical competence of locked plating augmented with supplemental intramedullary graft in comparison to conventional locked plate fixation in proximal humerus fractures (PHF). METHODS: Complex four-part PHFs were set in 30 artificial humeri assigned to 3 study groups (n = 10 in each group). Group 1 was characterized by loss of medial support, group 2 by simulated severe cancellous bone damage due to osteoporosis, and group 3 by combination of the 2 features. After locked plating, each specimen underwent nondestructive quasi-static mechanical testing in 25 degrees lateral angulation under axial loading between 150 and 400 N in 50-N increments, accompanied by consecutive anteroposterior x-ray imaging. Subsequently, an additional 3D-printed intramedullary graft was inserted into each specimen and all tests were repeated. RESULTS: Grafting resulted in significantly higher axial stiffness compared with no graft in groups 1 and 3 (P < 0.01) but not in group 2 (P = 0.12). Nongrafted specimens represented significantly higher stiffness in group 2 compared with groups 1 and 3 (P < 0.01), whereas no significant differences were detected among the 3 groups in the grafted state (P > 0.99). Varus deformation decreased significantly in each group after graft insertion (P ≤ 0.04). Nongrafted specimens in group 2 showed significantly lower varus deformation compared with groups 1 and 3 (P ≤ 0.04). No significant differences were registered among the 3 groups after grafting (P ≥ 0.65). CONCLUSIONS: From a biomechanical perspective, locked plating augmented with intramedullary graft has the potential to increase significantly the stability against varus collapse in unstable PHFs when compared with conventional locked plate fixation.