Tissue scaffold architecture affects implant degradation and bone tissue regeneration: A novel in silico mechanobiological model analysing cell behavior, mechanical stress and degradation kinematics

RESEARCH ARTICLE Tissue scaffold architecture affects implant degradation and bone tissue regeneration: A novel in silico mechanobiological model analysing cell behavior, mechanical stress and degradation kinematics Adel Alshammari 1,2 , Fahad Alabdah1,2, Lutong Li1, Glen Cooper1* 1 Department of Mechanical and Aerospace Engineering, School of Engineering, University of Manchester, Manchester, United Kingdom, 2 Department of Mechanical Engineering, University of Ha’il, Ha’il, Kingdom of Saudi Arabia * Abstract OPEN ACCESS Citation: Alshammari A, Alabdah F, Li L, Cooper G (2026) Tissue scaffold architecture affects implant degradation and bone tissue regeneration: A novel in silico mechanobiological model analysing cell behavior, mechanical stress and degradation kinematics. PLoS One 21(5): e0349708. https:// doi.org/10.1371/journal.pone.0349708 Editor: Ali Mehboob, Khalifa University of Science and Technology, UNITED ARAB EMIRATES Received: December 8, 2025 Accepted: May 4, 2026 Published: May 28, 2026 Copyright: © 2026 Alshammari et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data availability statement: All code required to reproduce the computational model presented in this study is publicly available. The source code for the agent-based cell and degradation Synthetic bone tissue scaffold function is controlled by both material and architecture. Experimental biomaterial approaches have brought significant advances in scaffold function, but scaffold architecture has not been fully explored. There are many scaffold architecture design options which could be more efficiently evaluated using computational methods. The aim of this study is to introduce a novel mechanobiological computational model to assess the effect of implant degradation, bone formation, and the influence of bone loading. A finite element model of a synthetic bone tissue scaffold within a rat bone defect supported by a fixation plate was coupled with an agentbased cell and degradation model (both bulk and surface degradation). The approach was partially validated using in vivo experimental mass-loss data and tested in a case study examining four poly-L-lactic acid tissue scaffolds with varying architectures. The model was run for 90 days to calculate results on cell behaviour, tissue formation and scaffold degradation. The results showed that scaffold architecture strongly influences degradation and cellular behaviour, with a filament thickness of 0.6 mm yielding 39 mm³ of new bone formation compared to 18 mm³ in a filament thickness of 0.2 mm, representing an approximate 117% increase at day 90. Cell migration was increased in higher porosity scaffold architectures by 31% when changing from 20.9% (T4) to 54.7% (T1) porosity. The mechanobiological computational model is, to the authors’ knowledge, the first time that implant degradation kinetics, mechanical environment, and cellular behavior have been combined in an in silico approach. The results show the importance of scaffold architecture design in the function of bone healing aided by tissue scaffold technology, emphasizing the importance of shape as well as material to improve implant function. Future work should aim to improve degradation modelling to include localised pH, autocatalysis and varying degradation PLOS One | https://doi.org/10.1371/journal.pone.0349708 May 28, 2026 1 / 24 model is hosted in a GitHub repository and archived on Zenodo with a DOI to ensure permanent accessibility. Zenodo DOI: https:// doi.org/10.5281/zenodo.18893712 All other relevant data supporting the findings of this study are contained within the manuscript and its supporting information files. Funding: This research was funded through PhD scholarships from the University of Ha’il, Ha’il, Saudi Arabia. It has also been supported by the School of Engineering, University of Manchester. Competing interests: The authors have declared that no competing interests exist. rates due to chemical changes. Additionally, models should also include angiogenesis to account for the importance of revascularization in bone healing. 1. Introduction Globally there are approximately two million large bone fracture cases that occur every year [1,2]. The gold standard for solving these issues is autogenous bone grafts [3–5]. However, there are some drawbacks of this approach such as limited bone tissue availability, disease transmission, a higher rate of infections, and a requirement for secondary surgery. A jawbone, joint, femur, or any type of bone in the body is not completely solid; it has a porous internal structure. Among other functions, these pores allow the inflow of nutrition, providing good conditions for cells to grow and attach, showing the importance of the natural extracellular matrix microstructure. Following a biomimicry approach, an alternative solution is a synthetic bone graft created using a tissue scaffold approach, which has shown promising results [6] However, these artificial bone tissue scaffolds have some biological and mechanical requirements, such as biocompatibility, biodegradability, and porosity, to allow cell attachment, proliferation, and differentiation [7–10]. Both the material and the shape of tissue scaffolds are important to enable biological, mechanical and degradation function [11–16] A lot of valuable research has been conducted on bone graft materials, but less has been outworked on bone graft shape, yet shape is equally important to enable successful bone graft function. This is illustrated in Fig 1, which shows the relationships of function, material, shape, manufacture, and environment, which was first reported in the authors’ previous work [1]. Tissue scaffold shape, specifically pore architecture, is key to providing both mechanical and biological environments for cells. Larger scaffold pores enhance vascularization and cellular infiltration but often compromise mechanical strength, highlighting the need for a balance between biological performance and structural stability [17,18]. Triangular pore shapes showed better mechanical outcomes than circular pore shapes [11,19–21], and round pore shapes are less biologically functional than square pore shapes [13]. The microstructure design of scaffolds affects their functionality in addition to other factors such as the material and the site of fracture. Yet a full understanding of the effect of scaffold architecture on the mechanical and biological aspects of bone healing is still incomplete, meaning that the design space is underexplored, which would require a huge number of experiments. Other industries use a virtual prototyping method before making physical prototypes, which is different from tissue scaffold research, which focuses on an experimental approach, probably due to the lack (...truncated)