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Computer-assisted orthopedic interventions require surgery planning based on patient-specific three-dimensional anatomical models. The state of the art has addressed the automation of this planning process either through mathematical optimization or supervised learning, the former requiring a handcrafted objective function and the latter sufficient training data. In this paper, we propose a completely model-free and automatic surgery planning approach for femoral osteotomies based on Deep Reinforcement Learning which is capable of generating clinical-grade solutions without needing patient data for training. One of our key contributions is that we solve the real-world task in a simulation environment tailored to orthopedic interventions based on an analytical representation of real patient data, in order to overcome convergence, noise, and dimensionality problems. An agent was trained on simulated anatomy based on Proximal Policy Optimization and inference was performed on real patient data. A qualitative evaluation with expert surgeons and a complementary quantitative analysis demonstrated that our approach was capable of generating clinical-grade planning solutions from unseen data of eleven patient cases. In eight cases, a direct comparison to clinical gold standard (GS) planning solutions was performed, showing our approach to perform equally good or better in 80% (surgeon 1) respectively 100% (surgeon 2) of the cases.

After tendon rupture repair, two main problems may occur: re-rupture and adhesion formation. Suitable non-murine animal models are needed to study the healing tendon in terms of biomechanical properties and extent of adhesion formation. In this study 24 New Zealand White rabbits received a full transection of the Achilles tendon 2 cm above the calcaneus, sutured with a 4-strand Becker suture. Post-surgical analysis was performed at 3, 6 and 12 weeks. In the 6-week group, animals received a cast either in a 180 deg stretched position during 6 weeks (adhesion provoking immobilization), or were re-casted with a 150 deg position after 3 weeks (adhesion inhibiting immobilization), while in the other groups (3 and 12 weeks) a 180 deg position cast was applied for 3 weeks. Adhesion extent was analyzed by histology and ultrasound. Histopathological scoring was performed according to a method by Stoll et al. (2011), and the main biomechanical properties were assessed. Histopathological scores increased as a function of time, but did not reach values of healthy tendons after 12 weeks (only around 15 out of 20 points). Adhesion provoking immobilization led to an adhesion extent of 82.7±9.7%, while adhesion inhibiting immobilization led to 31.9±9.8% after 6 weeks. Biomechanical properties increased over time, however, they did not reach full strength nor elastic modulus at 12 weeks post-operation. Furthermore, the rabbit Achilles tendon model can be modulated in terms of adhesion formation to the surrounding tissue. It clearly shows the different healing stages in terms of histopathology and offers a suitable model regarding biomechanics because it exhibits similar biomechanics as the human flexor tendons of the hand.

Most spine fusion procedures involve the use of prosthetic fixation devices combined with autologous bone grafts rather than biological treatment. We had shown that spine fusion could be achieved by injection of bone morphogenetic protein-2 (BMP-2)-expressing mesenchymal stem cells (MSCs) into the paraspinal muscle. In this study, we hypothesized that posterior spinal fusion achieved using genetically modified MSCs would be mechanically comparable to that realized using a mechanical fixation. BMP-2-expressing MSCs were injected bilaterally into paravertebral muscles of the mouse lumbar spine. In one control group BMP-2 expression was inhibited. Microcomputed tomography and histological analyses were used to evaluate bone formation. For comparison, a group of mouse spines were bilaterally fused with stainless steel pins. The harvested spines were later tested using a custom four-point bending apparatus and structural bending stiffness was estimated. To assess the degree to which MSC vertebral fusion was targeted and to quantify the effects of fusion on adjacent spinal segments, images of the loaded spine curvature were analyzed to extract rigidity of the individual spinal segments. Bone bridging of the targeted vertebrae was observed in the BMP-2-expressing MSC group, whereas no bone formation was noted in any control group. The biomechanical tests showed that MSC-mediated spinal fusion was as effective as stainless steel pin-based fusion and significantly more rigid than the control groups. Local analysis showed that the distribution of stiffness in the MSC-based fusion group was similar to that in the steel pin fusion group, with the majority of spinal stiffness contributed by the targeted fusion at L3-L5. Our findings demonstrate that MSC-induced spinal fusion can convey biomechanical rigidity to a targeted segment that is comparable to that achieved using an instrumental fixation.

BACKGROUND: Among the numerous osteotomies for correction of hallux valgus, the modified chevron is known for its good intrinsic stability and the scarf for its large corrective potential. An intermediate design, the reversed-L osteotomy, has been developed to combine these competing biomechanical objectives. The purpose of this in vitro study was to compare the structural and local biomechanical performance of these three designs. METHODS: Stiffness, cortical bone strains (a factor relevant to bone remodeling), strength and failure mode of the scarf, modified chevron and reversed-L osteotomies were measured on human specimens in two different loading configurations. FINDINGS: The scarf osteotomy caused significant changes in stiffness and cortical bone strains with the proximal apex being at the origin of bone failure. The chevron and reversed-L had a generally comparable response to the intact bone. The chevron specimens failed by pivoting of the distal fragment, and the reversed-L by pivoting or fracture. INTERPRETATION: This is the first study to investigate the cortical bone strain changes induced by these invasive osteotomies. Alterations from the intact bone response could be directly related to the design of the osteotomy. Notably, the critical weakening proximal apex of the scarf is avoided in the reversed-L, leading to results comparable to the chevron. This study provides support in favor of the intermediate design of the reversed-L as an effective compromise between the competing biomechanical objectives of corrective potential and mechanical stability.

Predictive numerical models of cellular response to biophysical cues have emerged as a useful quantitative tool for cell biology research. Cellular experiments in silico can augment in vitro and in vivo investigations by filling gaps in what is possible to achieve through 'wet work'. Biophysics-based numerical models can be used to verify the plausibility of mechanisms regulating tissue homeostasis derived from experiments. They can also be used to explore potential targets for therapeutic intervention. In this perspective article we introduce a single cell model developed towards the design of novel biomaterials to elicit a regenerative cellular response for the repair of diseased tissues. The model is governed by basic mechanisms of cell spreading (lamellipodial and filopodial extension, formation of cell-matrix adhesions, actin reinforcement) and is developed in the context of cellular interaction with functionalized substrates that present defined points of potential adhesion. To provide adequate context, we first review the biophysical underpinnings of the model as well as reviewing existing cell spreading models. We then present preliminary benchmarking of the model against published experiments of cell spreading on micro-patterned substrates. Initial results indicate that our mechanistic model may represent a potentially useful approach in a better understanding of cell interactions with the extracellular matrix.

Fibered confocal laser scanning microscopes have given us the ability to image fluorescently labeled biological structures in vivo and at exceptionally high spatial resolutions. By coupling this powerful imaging modality with classic optical elastography methods, we have developed novel techniques that allow us to assess functional mechanical integrity of soft biological tissues by measuring the movements of cells in response to externally applied mechanical loads. Using these methods we can identify minute structural defects, monitor the progression of certain skeletal tissue disease states, and track subsequent healing following therapeutic intervention in the living animal. Development of these methods using a murine Achilles tendon model has revealed that the hierarchical and composite anatomical structure of the tendon presents various technical challenges that can confound a mechanical analysis of local material properties. Specifically, interfascicle gliding can yield complex cellular motions that must be interpreted within the context of an appropriate anatomical model. In this study, we explore the various classes of cellular images that may result from fibered confocal microscopy of the murine Achilles tendon, and introduce a simple two-fascicle model to interpret the images in terms of mechanical strains within the fascicles, as well as the relative gliding between fascicles.