Advances in Biomaterials for Promoting Vascularization

Purpose of Review: Tissue engineered constructs (TECs)—commonly developed using natural or synthetic biomaterials—are crucially needed for addressing the shortage of organ donations, immune rejection of transplants, pre-clinical in vitro drug efficacy testing, evaluation of personalized therapy options, and development of cell-laden substitutes for regenerative therapies. Unfortunately, constructs thicker than 200 microns suffer from poor diffusion rates of oxygen and nutrients needed for the survival of embedded cells as well as compliance of nearby tissue. To circumvent this challenge, biomaterials that promote vascularization are of upmost significance in the field of regenerative medicine. This article serves to review the current biomaterials (natural and synthetic) commonly utilized in the past few years to initiate and promote vascularization of TECs. Recent Findings: Natural biomaterials have greater bioactivity compared to synthetic biomaterials; however, they suffer from uncontrollable rates of biodegradation, lack of batch-to-batch reproducibility, and low mechanical strength. Synthetic biomaterials, although also biocompatible and non-immunogenic, offer superior tunable mechanical strength and slow biodegradation rates. In the past few years, researchers have focused on making composite materials (combining natural and synthetic biomaterials or combining biomaterials with chemical additives), performing chemical modifications to circumvent subpar material performance properties, or utilizing techniques like electrospinning to fabricate fibrous networks resembling native ECM to promote vascularization. Summary: The works reviewed in this article illustrate a variety of chemically, structurally, or compositionally modified natural and/or synthetic biomaterials capable of promoting vascularization of TECs. We believe future efforts in this avenue should include (1) methacrylation of dECM components, (2) inclusion of pre-vascularized constructs using on-chip technologies, (3) immobilization/integration of soluble angiogenic factors, (4) exploration of more versatile chemically modifications, (5) utilization of more non-cytotoxic crosslinking agents, (6) electrospinning technologies to mimic ECM architecture, and (7) implementation of additional environmental/structure factors to promote vascularization.