Tissue Engineered Neurovascularization Strategies for Craniofacial Tissue Regeneration

Abstract

Craniofacial tissue injuries, diseases, and defects, including those within bone, dental, and periodontal tissues and salivary glands, impact an estimated 1 billion patients globally. Craniofacial tissue dysfunction significantly reduces quality of life, and successful repair of damaged tissues remains a significant challenge. Blood vessels and nerves are colocalized within craniofacial tissues and act synergistically during tissue regeneration. Therefore, the success of craniofacial regenerative approaches is predicated on successful recruitment, regeneration, or integration of both vascularization and innervation. Tissue engineering strategies have been widely used to encourage vascularization and, more recently, to improve innervation through host tissue recruitment or prevascularization/innervation of engineered tissues. However, current scaffold designs and cell or growth factor delivery approaches often fail to synergistically coordinate both vascularization and innervation to orchestrate successful tissue regeneration. Additionally, tissue engineering approaches are typically investigated separately for vascularization and innervation. Since both tissues act in concert to improve craniofacial tissue regeneration outcomes, a revised approach for development of engineered materials is required. This review aims to provide an overview of neuro­vascularization in craniofacial tissues and strategies to target either process thus far. Finally, key design principles are described for engineering approaches that will support both vascularization and innervation for successful craniofacial tissue regeneration.

Functionalized hydrogel–microsphere composites stimulating neurite outgrowth for vascularized bone regeneration

“…Previous studies have inferred that osteoblasts and neurons may secrete some bioactive factors for signal transduction and regulation. 28 In this study, by collecting the conditioned medium (CM), the influence and mechanism of osteoblasts and neurons on ECs were preliminarily discussed. The hMSCs differentiated into osteoblasts, and the CM was beneficial for the healing of scratches, indicating that the osteoblasts may secrete bioactive factors to stimulate the migration of human umbilical vein endothelial cells (HUVECs) (Fig.…”

“…Previous studies have inferred that osteoblasts and neurons may secrete some bioactive factors for signal transduction and regulation. 28 In this study, by collecting the conditioned medium (CM), the influence and mechanism of…”

MicroCT-based imaging of microvasculature within bone and peri-implant tissues

“…There is an understanding in the bone biology, tissue engineering and related research fields, that adequate vascularization is a prerequisite for successful bone formation and regeneration as well as osseointegration of biomaterials (Li et al, 2022, Schott et al, 2021, Sivaraj and Adams, 2016, Wernike et al, 2010, Chandra and Atala, 2019). To influence or even control these processes, the interplay between vascular and bone tissue should be studied at the most detailed imaging level available.…”

Endothelial cells during craniofacial development: Populating and patterning the head

“…Instructions from the vasculature are also required for tissue engineering strategies to encourage repair and regeneration of cranial tissue. In keeping with this need, new tissue engineering strategies are being developed to encourage vascularisation of cranial tissue, either through host tissue recruitment or pre-vascularisation of engineered tissue ( Li et al, 2022 ). For enhanced repair and to simulate regeneration, there is much to be learn from understanding the expanding role of endothelial cells in cranial development.…”