New insights into the biomimetic design and biomedical applications of bioengineered bone microenvironments

Abstract

The bone microenvironment is characterized by an intricate interplay between cellular and noncellular components, which controls bone remodeling and repair. Its highly hierarchical architecture and dynamic composition provide a unique microenvironment as source of inspiration for the design of a wide variety of bone tissue engineering strategies. To overcome current limitations associated with the gold standard for the treatment of bone fractures and defects, bioengineered bone microenvironments have the potential to orchestrate the process of bone regeneration in a self-regulated manner. However, successful approaches require a strategic combination of osteogenic, vasculogenic, and immunomodulatory factors through a synergic coordination between bone cells, bone-forming factors, and biomaterials. Herein, we provide an overview of (i) current three-dimensional strategies that mimic the bone microenvironment and (ii) potential applications of bioengineered microenvironments. These strategies range from simple to highly complex, aiming to recreate the architecture and spatial organization of cell–cell, cell-matrix, and cell-soluble factor interactions resembling the in vivo microenvironment. While several bone microenvironment-mimicking strategies with biophysical and biochemical cues have been proposed, approaches that exploit the ability of the cells to self-organize into microenvironments with a high regenerative capacity should become a top priority in the design of strategies toward bone regeneration. These miniaturized bone platforms may recapitulate key characteristics of the bone regenerative process and hold great promise to provide new treatment concepts for the next generation of bone implants.

The Osteoinductivity of Calcium Phosphate-Based Biomaterials: A Tight Interaction With Bone Healing

“…They secrete a series of pro-inflammatory cytokines [e.g., tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), IL-6], which in turn recruit mesenchymal stem cells (MSCs), osteoprogenitor cells, and fibroblasts for tissue repair ( Miron et al, 2016 ; Zhu et al, 2021 ). Macrophages transform towards M2 wound-healing type at the end of the inflammatory stage and secrete anti-inflammatory cytokines [e.g., IL-4, IL-10, and transforming growth factors beta (TGF-β)] in favor of establishing osteogenic environments ( Oliveira et al, 2021 ).…”

Emerging modulators for osteogenic differentiation: a combination of chemical and topographical cues for bone microenvironment engineering

“…The progress in the field could open new avenues of instructive biomaterials that could be used in bone regeneration, without the need of using cells, and therefore decreasing the complexity of the therapeutical solution and accelerating the translation into the clinics. 2…”

“…Over the past few decades, BTE has pursued different strategies to better mimic the native environment aiming to create autonomous bioengineering platforms. 2 With increasing knowledge of the impact of chemical and biophysical signals on cells, researchers have developed platforms with cues to improve cell attachment, proliferation, cell–cell communication, migration, osteogenesis, and mineralization.…”

“…The deeper understanding of the bone physiology and biology has enabled the identification of crucial aspects that can be inscribed in biomaterials or biomedical devices. 1,2 For that, numerous strategies involving biomaterials modifications, namely chemical and topographical, have emerged for the bioengineering of structures able to create ideal microenvironments for autonomous and self-regulated osteogenesis.…”

Repair of Large-Scale Rib Defects Based on Steel-Reinforced Concrete-Designed Biomimetic 3D-Printed Scaffolds with Bone-Mineralized Microenvironments

“…An ideal BBS for large-scale rib reconstruction simultaneously has the following properties: controllable three-dimensional morphology, proper mechanical properties, good biocompatibility and biodegradability, porous structure suitable for cell loading, and a biomimetic osteogenic microenvironment. , The development of 3D-printing technology has enabled the three-dimensional morphology and mechanical properties of scaffolds to be controlled accurately through the computer-aided design (CAD) of high-molecule polymers . Porosity, biocompatibility, and biodegradability could also be achieved through the freeze drying and cross linking of naturally degradable materials .…”