A Perspective on the Clinical Translation of Scaffolds for Tissue Engineering

Abstract

Scaffolds have been broadly applied within tissue engineering and regenerative medicine to regenerate, replace, or augment diseased or damaged tissue. For a scaffold to perform optimally, several design considerations must be addressed, with an eye toward the eventual form, function, and tissue site. The chemical and mechanical properties of the scaffold must be tuned to optimize the interaction with cells and surrounding tissues. For complex tissue engineering, mass transport limitations, vascularization, and host tissue integration are important considerations. As the tissue architecture to be replaced becomes more complex and hierarchical, scaffold design must also match this complexity to recapitulate a functioning tissue. We outline these design constraints and highlight creative and emerging strategies to overcome limitations and modulate scaffold properties for optimal regeneration. We also highlight some of the most advanced strategies that have seen clinical application and discuss the hurdles that must be overcome for clinical use and commercialization of tissue engineering technologies. Finally, we provide a perspective on the future of scaffolds as a functional contributor to advancing tissue engineering and regenerative medicine.

How to use BMP-2 for clinical applications? A review on pros and cons of existing delivery strategies

“…The cohort expressing both growth factors simultaneously was found to be better in terms of the formation and deposition of newly formed bone compared to the cohorts expressing only one of the two growth factors in rabbit orbital defect model [72]. The delivery of VEGF in combination with the osteogenic BMP-2 induces neo-vascularization of the newly formed bone tissue thus enabling superior supply of nutrients [73].…”

On the Automatic Decellularisation of Porcine Aortae: A Repeatability Study Using a Non-Enzymatic Approach

“…The efficacy of manual decellularisation has been demonstrated successfully by numerous groups, and manually prepared xenogenic-derived tissue substitutes have been used in clinical practice for many years; however, little attention has been directed towards their 'upscaled' production [Badylak, 1989;Price et al, 2014;G et al, 2015;Webber et al, 2015]. In this current ex vivo study, a comparative analysis of the repeatable nature of ADP, which was previously described for the preparation of ovine aortaderived ECMs, was investigated using Triton X-100 as the main active decellularisation reagent [Mooney et al, 2015].…”

“…As decellularised extracellular matrices (ECMs) become more relevant in delivering these advanced tissue therapies, automation of the decellularisation process will ultimately be required to provide for the increasing number of patients and also at an affordable sustainable price for world health care providers [G et al, 2015]. Various authors such as G et al [2015] and Webber et al [2015] have suggested that one of the principal reasons that so little clinical translation has occurred to date is due to the extremely high costs of delivering such treatments and also the lack of availability of quality-assured consistent ECMderived scaffolds for implantation and research purposes Price et al, 2014;G et al, 2015;Webber et al, 2015]. They have suggested that 'up-scaled' production is one key area that needs greater investigation, to ensure cost-effectively decellularised ECM scaffolds which can safely be used to treat a much larger cohort of patients [WHO, 2013;G et al, 2015;Webber et al, 2015].…”

“…Various authors such as G et al [2015] and Webber et al [2015] have suggested that one of the principal reasons that so little clinical translation has occurred to date is due to the extremely high costs of delivering such treatments and also the lack of availability of quality-assured consistent ECMderived scaffolds for implantation and research purposes Price et al, 2014;G et al, 2015;Webber et al, 2015]. They have suggested that 'up-scaled' production is one key area that needs greater investigation, to ensure cost-effectively decellularised ECM scaffolds which can safely be used to treat a much larger cohort of patients [WHO, 2013;G et al, 2015;Webber et al, 2015]. Limitations associated with xenogenic ECMs include the absence of gold standard preparation techniques for a repeatable decellularisation process, compounded by the fact that decellularisation is performed manually, lacking standardisation and is extremely time consuming [Naso et al, 2014;Price et al, 2014].…”

“…A large research effort has been applied to the development of newer alternatives to current gold standard treatments for tissue and organ failure, using these tissue engineering approaches [Pellegata et al, 2012;WHO, 2013;Price et al, 2014;G et al, 2015;Webber et al, 2015]. Although decellularised xenogenic scaffolds promise to deliver more effective outcomes than the current gold standard treatments, very little of the current research effort has been translated into clinical practice, although major milestones have been achieved, such as the world's first decellularised trachea replacement by Macchiarini et al [2008].…”