Calcium phosphate cement scaffold with stem cell co-culture and prevascularization for dental and craniofacial bone tissue engineering
Introduction
The need for dental, craniofacial and orthopedic repairs and regeneration is increasing rapidly as the world population ages. Bone tissue engineering strategies employ scaffolds, growth factors and stem cells for bone regeneration [1,2]. Scaffolds provide a special environment for cell migration and proliferation, and serve as vehicles to deliver growth factor [3,4]. The criteria for a suitable scaffold include: (1) biocompatibility to avoid immune response in the implant area; (2) biodegradability to facilitate bone remodeling; (3) mechanical properties to support defect reconstruction; (4) microarchitecture for stress distribution; (5) osteoinductivity for osteogenic differentiation; (6) porosity for neovascularization and osteogenesis; and (7) surface properties that induce cell migration, proliferation and differentiation [5].
Calcium phosphate cements are bone mineral-mimicking scaffolds that are injectable, load-bearing, biocompatible, bioactive, and resorbable [6,7]. They are promising for dental, craniofacial and orthopedic applications due to their moldability to achieve esthetics, which is especially important for dental and maxillofacial applications. The first calcium phosphate cement consisted of tetracalcium phosphate [Ca4(PO4)2O] and dicalcium phosphate anhydrous (CaHPO4), and was referred to as CPC. Since then, other calcium phosphate cements were developed [8,9]. CPC can adapt to the defect shapes and possess better mechanical strength when compared with hydrogels and other injectable polymers [10,11]. Moreover, CPC can be fabricated as a tailored structure at the micro- and nano-scale, and can allow protein adsorption and cell adhesion to enhance the bone repair process [8].
Besides orthopedic applications, potential dental and craniofacial applications of CPC scaffolds with improved cell adhesion and prevascularization include mandibular and maxillary ridge augmentation, because the CPC paste could be easily molded and contoured to achieve an esthetic shape and then harden in situ. In addition, major reconstructions of the maxilla or mandible after trauma or tumor resection would greatly benefit from a moldable CPC with rapid osteoconduction and prevascularization. Furthermore, periodontal regeneration, the support of metal dental implants and the augmentation of deficient implant sites could all benefit from injectable and moldable CPC scaffolds. However, currently, there are several major challenges facing the use of scaffolds in clinical applications, including: (1) inadequate vascularization, especially in large defects; (2) poor osseointegration; (3) infection; (4) uncertain degradability; and (5) low stiffness and strength [5]. Among them, vessel formation is the most pressing challenge in bone regeneration. Insufficient vascularization leads to inadequate oxygen and nutrition supply, thus causing hypoxia and cell death [12]. This article reviews various novel strategies for the vascularization of CPC scaffolds for bone tissue engineering, including reviewing for the first time the bi-culture and tri-culture with CPC scaffolds for bone regeneration in dental, craniofacial and orthopedic applications.
Section snippets
Vascularization in bone tissue engineering
Vascularization is one of the main challenges that must be overcome in bone tissue engineering. The current strategies are mainly characterized in two aspects: the use of angiogenic growth factors; and prevascularization of scaffolds in vitro.
Co-culture strategy for prevascularization
Early stages of blood vessels are significant for bone regeneration. Capillary-like structures formed in vitro could integrate rapidly after implantation in vivo to become functioning blood vessels. Endothelial cells are able to produce capillary-like structures and are promising for bone vascularization. However, the primary vascular structure fabricated by endothelial cells is usually fragile and unstable [28]. In addition, endothelial cells themselves cannot produce specific pro-angiogenic
Tri-culture strategy for prevascularization
Despite the encouraging results regarding bone-forming cells and vessel-forming cells [66], the co-culture approach could have problems such as the stability and maturation of the primary vascular network during bone vascularization [67]. Perivascular cells such as pericytes could act in an important role during tissue engineering by providing physical support for the endothelial cells and by the expression of key angiogenic factors [68,69]. The vascularization started with the recruitment of
Conclusions
This article represents the first review on bi-culture and tri-culture of CPC scaffolds with stem cells to promote vascularization and enhance bone regeneration for dental, craniofacial and orthopedic applications. Macroporous CPC scaffolds are nano-mineral bone cements that are promising for bone tissue engineering due to their load-bearing ability, bone mineral-mimicking ability, bioactivity, and affinity for cell seeding. RGD-CPC scaffolds exhibited better performance in enhancing cell
Acknowledgments
This study was supported by NIH R01 DE17974 (HX), a Seed Grant (HX) from the University of Maryland and a bridge grant (HX) from University of Maryland School of Dentistry.
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2023, Engineered RegenerationCitation Excerpt :For the proper development of the skeleton, bone undergoes dynamic modeling and remodeling processes, including the development of bone formation and resorption. There is an increasing demand for dental, craniofacial, and orthopedic regeneration and repair as the world's elderly population grows [1]. Oral and craniofacial bone lesions vary considerably from small bony defects, namely periodontal and peri-implant defects, to severe and significant defects brought on by trauma, tumor excision, and congenital deformities, affecting aesthetic appearance and functionality [2].
Role of nanostructured materials in hard tissue engineering
2022, Advances in Colloid and Interface ScienceCitation Excerpt :Since its discovery in 1990 by Brown et al [35], self-setting bone cements based on calcium phosphate have attracted considerable attention in the scientific community. Its applications extended to be used in the construction of new nanostructured scaffolds that act as stable tissue support and as a regeneration inducer [36,37]. The applications of calcium phosphate cements, CPCs, in bone tissue repair have their origin in the fact that the not exothermic reaction of their components at physiological temperature (37°C) in aqueous solution leads to the formation of crystalline hydroxyapatite (HA).
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