Jul 2026· Tissue engineering. Part B, Reviews· pp.
19373368261460324
· 0 citations· 87 references
Medicine
TL;DR
This review critically examines the mechanobiological design of bioinspired polymeric scaffolds and discusses the role of computational modeling in predicting scaffold performance and highlights emerging technologies, including 4D printing and piezoelectric scaffolds, which offer time-dependent and mechano-electrical adaptability.
Abstract
Bone regeneration presents a significant clinical challenge due to the complex interplay between biological processes and the local mechanical environment. While polymeric scaffolds are widely utilized for their tunable physicochemical properties, traditional designs often fail to replicate the dynamic mechanical cues required for optimal tissue remodeling. This review critically examines the mechanobiological design of bioinspired polymeric scaffolds. We first categorize native bone mechanics and the role of mechanical stimuli-such as stiffness, fluid shear, and stability-in regulating the fracture healing cascade. We then bridge these biological principles with advanced fabrication strategies, analyzing how natural, synthetic, and composite polymers can be engineered to mimic the hierarchical stiffness and bioactivity of native bone. Furthermore, we discuss the role of computational modeling (e.g., Finite Element Analysis) in predicting scaffold performance and highlight emerging technologies, including 4D printing and piezoelectric scaffolds, which offer time-dependent and mechano-electrical adaptability. Finally, we address current barriers to clinical translation and propose future directions for mechanically adaptive systems that actively guide regeneration.
This review examines the mechanobiological mechanisms by which smart nanocomposite scaffolds regulate bone regeneration, with particular emphasis on interactions between scaffolds and stem cells, immune modulation, angiogenic coupling, and translational feasibility.
Piezoelectric hydrogels have emerged as a class of biomaterials that have garnered significant attention in bone tissue engineering in recent years. Their unique property lies in their ability to generate electrical charges under mechanical deformation. This piezoelectric effect is key to enhancing bone regeneration by mimicking the natural mechanical forces that stimulate osteogenesis in vivo. With their high water content, elasticity, biocompatibility, and capacity to modulate cellular responses through electrical stimulation (ES), they present an ideal choice for bone defect repair. Recent studies have demonstrated that ES can significantly promote osteoblast differentiation and bone formation, making piezoelectric hydrogels a critical factor in facilitating bone tissue regeneration. By integrating piezoelectric materials into hydrogels, they not only support cell growth but also actively promote bone healing through mechanoelectrical signaling. Specifically, this review (i) quantifies the range of piezoelectric coefficients and electrical outputs reported for hydrogels, (ii) critically compares fabrication methods with their scalability limitations, and (iii) outlines design guidelines for achieving stable, clinically translatable piezoelectric systems. By bridging materials science and bioelectric medicine, this review provides a roadmap for developing next-generation bone repair scaffolds. Unlike previous narrative reviews, our work provides a critical comparative assessment—quantitatively comparing piezoelectric coefficients, fabrication scalability, and translational bottlenecks.
Electroactive biomaterials represent a promising strategy for reconstructing the electrobiological microenvironment of bone and enhancing tissue regeneration. Among these materials, poly(3,4-ethylenedioxythiophene) (PEDOT) and its composites have attracted considerable attention because of their mixed electronic and ionic conductivity and compatibility with soft and porous scaffolds. However, existing reviews rarely address how fabrication strategies govern the relationships between structure, properties, and translational performance. This review establishes a fabrication, performance, and translation framework for PEDOT-based bone repair systems. Fabrication strategies are categorized into interfacial polymerization, bulk matrix and solution-processed conductive networks, patterned and fibrous conductive architectures, and porous and 3-dimensional scaffold fabrication and are correlated with conductive network topology, mechanical performance, and cytocompatibility. The mechanistic roles of PEDOT in osteogenesis, angiogenesis, immunomodulation, and electroresponsive drug release are further summarized. In addition, this review discusses the key trade-offs that limit practical applications, including the balance between conductivity and degradability, mechanical strength and porosity, as well as multifunctionality and manufacturability. Overall, this review provides a framework-oriented perspective to guide the rational design and clinical translation of PEDOT-based bioelectronic materials for bone tissue engineering.
Bone defects, especially critical-sized bone defects, still remain a major challenge due to limited intrinsic regenerative capacity. Limitations in biomimetic structure and functional performance in existing bone repair materials motivate the development of multifunctional osteogenic scaffolds. Herein, hierarchical topological nanofibrous mats (HTNFMs) functionalized with triple-helical piezoelectric collagen fibrils (PECFs, d33 = 9.92 pm V-1) were fabricated, with gradient PECF loadings of 5, 10, and 20 wt‰. Quantitative cellular assays verify that the 10 wt‰ PECF-modified group (HTNFM-10) achieves the optimal osteogenic performance, with alkaline phosphatase activity and extracellular mineral deposition reaching 1.82-fold and 2.16-fold of pure polycaprolactone (PCL) substrates, respectively. This unique structural design enables HTNFMs to create a multimodal extracellular osteogenic microenvironment with synergistic structural, mechanical, and electrical cues. Benefiting from their intrinsic piezoelectricity, HTNFMs can effectively convert endogenous cell traction forces and physiological external mechanical stimuli into bioelectric signals in situ, independent of external power sources, while providing biomimetic mechanical support for cell adhesion and tissue regeneration. The synergistic regulation of multiple microenvironmental cues significantly promotes osteogenic differentiation of bone marrow mesenchymal stem cells in vitro and accelerates bone regeneration in vivo. Furthermore, transcriptomic analysis revealed that the multimodal extracellular osteogenic microenvironment constructed by HTNFMs activates intracellular calcium signaling cascades to mediate the upregulation of osteogenic-related genes. This work proposes a self-stimulating novel piezoelectric biomimetic design strategy and validates HTNFMs as a promising platform for complex bone defect repair.
Xiaotong Wang, Xiaofeng Hu, Ruiqi Sheng et al.· Journal of materials chemist...· 0 citations
Clinical repair of bone defects has long faced challenges including the limited availability of autografts, immunological rejection of allografts, and mechanical mismatch of traditional implants. Injectable hydrogels have emerged as highly promising strategies in bone tissue engineering due to their unique advantages: minimally invasive implantation, the ability to conform to irregular defect cavities, excellent biocompatibility, and high functional tunability. This review systematically outlines recent advances in injectable hydrogels for bone regeneration. It comprehensively outlines material classifications and fundamental properties. Specifically, it analyzes key design strategies, including enhancing mechanical support through cross-linking optimization and the incorporation of reinforcing phases, reconstructing the regenerative microenvironment via bioactive factor loading, and enabling synchronized degradation and tissue regeneration. Furthermore, this review summarizes current applications for different bone defect types, identifies current technical bottlenecks such as balancing mechanical strength with minimally invasive delivery, and anticipates future directions, including stimuli-responsive design and multifunctional integration.
Xin-Yue Zhang, Zhen-Shun Zhuang, Bo Liu et al.· RSC Advances· 0 citations
Current challenges, emerging trends, and future directions in the development of next-generation biomaterials that integrate biochemical and physicomechanical approaches for clinical applications in bone repair and regeneration are discussed.
Bofeng Pan, Adam Maalal, D. Hao· International Journal of Mol...· 0 citations
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