Advancing application of mesenchymal stem cell-based bone tissue regeneration

Abstract

Reconstruction of bone defects, especially the critical-sized defects, with mechanical integrity to the skeleton is important for a patient's rehabilitation, however, it still remains challenge. Utilizing biomaterials of human origin bone tissue for therapeutic purposes has provided a facilitated approach that closely mimics the critical aspects of natural bone tissue with regard to its properties. However, not only efficacious and safe but also cost-effective and convenient are important for regenerative biomaterials to achieve clinical translation and commercial success. Advances in our understanding of regenerative biomaterials and their roles in new bone formation potentially opened a new frontier in the fast-growing field of regenerative medicine. Taking inspiration from the role and multicomponent construction of native extracellular matrix (ECM) for cell accommodation, the ECM-mimicking biomaterials and the naturally decellularized ECM scaffolds were used to create new tissues for bone restoration. On the other hand, with the going deep in understanding of mesenchymal stem cells (MSCs), they have shown great promise to jumpstart and facilitate bone healing even in diseased microenvironments with pharmacology-based endogenous MSCs rescue/mobilization, systemic/local infusion of MSCs for cytotherapy, biomaterials-based approaches, cell-sheets/-aggregates technology and usage of subcellular vesicles of MSCs to achieve scaffolds-free or cell-free delivery system, all of them have been shown can improve MSCs-mediated regeneration in preclinical studies and several clinical trials. Here, following an overview discussed autogenous/allogenic and ECM-based bone biomaterials for reconstructive surgery and applications of MSCs-mediated bone healing and tissue engineering to further offer principles and effective strategies to optimize MSCs-based bone regeneration.

Keywords: Biomaterials; Bone healing; Cell-sheets/ -aggregates; Cytotherapy; Exosomes; Extracellular matrix; Mesenchymal stem cells; Regenerative medicine.

Fig. 1

MSCs contributions to bone remodeling and pathology.

Fig. 2

Schematic representation of bone tissue grafts of natural origin bone graft substitutes for pre/clinical therapeutics (examples are given where appropriate; illustrations are Not to scale). Bone tissues for transplantation include autologous bone grafts (A), autologous cancellous bone grafts (B), allogeneic bone allografts (C), allogeneic bone grafting materials produced product (D), demineralized bone matrix (DBM) (E), bone decellularized ECM (bdECM) (F) and calcined bovine bone (CBB) (G). The images used here are selected samples for schematic representation only; they do not represent any particular preference by pre/clinicians. Source: Figure components B, C, D and F reproduced with permission from the authors; the remaining components are by the corresponding author's, or from unpublished resources from the corresponding author's institution.

Fig. 3

Schematic of human-derived mesenchymal stem cells for cytotherapy and tissue engineering applications (Taking bone marrow mesenchymal stem cells for example, schematic is not to scale).

Fig. 4

Inflammatory microenvironment impairs resident MSCs and solutions.