OMIBONE: Omics-driven computer model of bone regeneration for personalized treatment

Treatment of bone fractures are commonly standardized, neglecting individual differences due to patient's healing potential or accompanying diseases. This study introduces a novel framework that allows to predict bone regeneration outcome using combined proteomic and mechanical analyses in a computer model. The framework uses Ingenuity Pathway Analysis (IPA) software to link protein changes to alterations in biological processes and integrates these in an Agent-Based Model (ABM) of bone regeneration. The computer model predicted the progression of bone formation patterns in a mouse femur fracture stabilized with an intramedullary pin. The developed framework holds promise as a concept to enable personalized bone healing predictions.

Reference: Mahdi Jaber, Johannes Schmidt, Stefan Kalkhof, Louis Gerstenfeld, Georg N Duda, Sara Checa OMIBONE: Omics-driven computer model of bone regeneration for personalized treatment. Bone. 2024 Oct 17:117288. doi: 10.1016/j.bone.2024.117288. PMID: 39426580.

PCL strut-like scaffolds appear superior to gyroid in terms of bone regeneration within a long bone large defect: An in silico study

The treatment of large bone defects represents a major clinical challenge, where 3D printed scaffolds appear as a promising strategy to support bone defect regeneration. This study investigated whether gyroid scaffolds, characterized by a zero mean surface curvature, present advantages over traditional strut-like scaffolds in terms of their bone regeneration potential in large bone defects. Using a validated in silico modeling approach, bone regeneration within both scaffolds designs was simulated. Simulation results showed that the large surface curvatures of the gyroid scaffold leads to a slower tissue formation dynamic and as a result reduced bone regeneration compared with strut-like designs. Contrary to initial assumptions, gyroid scaffolds did not improve healing. These results highlight the potential of computational approaches for optimizing scaffold designs in pre-clinical stages.

Reference: Mahdi Jaber, Patrina Poh, Georg Duda, Sara Checa. PCL strut-like scaffolds appear superior to gyroid in terms of bone regeneration within a long bone large defect: An in silico study. Front Bioeng Biotechnol. 2022 Sep 23;10:995266. doi: 10.3389/fbioe.2022.995266. PMID: 36213070; PMCID: PMC9540363.

External mechanical loading overrules cell-cell mechanical communication in sprouting angiogenesis during early bone regeneration

Sprouting angiogenesis – the process by which new blood vessel sprout off from existing vasculature – is essential for bone regeneration. Endothelial cells within vessels are known to interact mechanically with their surroundings, such as outer-vascular stromal cells, through cell-induced traction forces. Simultaneously, external physiological loads cause tissue deformations at the healing site impacting cellular arrangements. However, the relative influence of these two mechanical cues – cell-induced and external – on angiogenesis during early bone healing remains unclear. This study used an in silico modelling approach to explore how these mechanical signals shape sprout patterns during early bone healing. The model incorporated the mechano-regulation of sprouting angiogenesis and stromal cell organization, and its predictions were compared to in vivo experiments using a mouse osteotomy model stabilized with rigid or semirigid fixation. Results showed that the magnitude and orientation of principal strains within the healing region can explain experimentally observed sprout patterning, under both fixation conditions. Simulations revealed that external mechanical signals dominate over the local cell-mediated mechanical communication. Such findings illustrate the relevance of external mechanical signals in guiding angiogenesis and could inform fracture treatment strategies to enhance bone regeneration.

Reference: Chiara Dazzi,Julia Mehl,Mounir Benamar,Holger Gerhardt,Petra Knaus,Georg N. Duda,Sara Checa doi: 10.1371/journal.pcbi.1011647

Reduced Bone Regeneration in Rats With Type 2 Diabetes Mellitus as a Result of Impaired Stromal Cell and Osteoblast Function-A Computer Modeling Study

The ability of bones to self‐regenerate is impaired in Type 2 Diabetes Mellitus (T2DM). T2DM is a metabolic disease associated with reduced bone regeneration capability, high fracture risk, and a high incidence of non‐unions. Both mechanical and biological factors have been associated with the reduced bone regeneration response, however their relative contribution to the impair healing remains largely unknown. This study investigated whether reduced healing in T2DM results primarily from mechanical or cellular alterations. A previously validated in silico computer model of bone regeneration was further developed to incorporate T2DM-related mechanical and cellular alterations in bone regeneration.  The computer model showed that mechanical alterations had little effect on the reduced bone regeneration in T2DM and that alterations in MSC proliferation, MSC migration, and osteoblast differentiation had the highest effect. These findings could have clinical implications in the treatment of bone fractures in patients with T2DM.

Reference: Mahdi Jaber, Lorenz C Hofbauer, Christine Hofbauer, Georg N Duda, Sara Checa. Reduced Bone Regeneration in Rats With Type 2 Diabetes Mellitus as a Result of Impaired Stromal Cell and Osteoblast Function-A Computer Modeling Study. JBMR Plus. 2023 Oct 2;7(11):e10809. doi: 10.1002/jbm4.10809. PMID: 38025037; PMCID: PMC10652174.

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