Leading Approaches to Vascularize Kidney Constructs in Tissue Engineering

There is an unprecedented need for new treatments for renal failure,as the incidence of this disease is increasing disproportionately to advancements in therapies.Current treatments are limited by the availability of viable organs,for which there is a worldwide lack.These treatment modalities also require a substantial amount of infrastructure,significantly limiting the access to care in most countries.Kidney tissue engineering approaches promise to develop alternative solutions that address many of the inadequacies in current care.Although many advancements have been made—primarily in the past decade—in biofabrication and whole-organ tissue engineering,many challenges remain.One major hindrance to the progress of current tissue engineering approaches is establishing successful vascularization of developed engineered tissue constructs.This review focuses on the recent advancements that address the vascular challenge,including the biofabrication of vasculature,whole-organ engineering through decellularization and recellularization approaches,microscale organogenesis,and vascularization using organoids in the context of kidney tissue engineering.We also highlight the specific challenges that remain in developing successful strategies capable of clinical translation.

Bioreactor design and validation for manufacturing strategies in tissue engineering

The fields of regenerative medicine and tissue engineering offer new therapeutic options to restore,maintain or improve tissue function following disease or injury.To maximize the biological function of a tissue-engineered clinical product,specific conditions must be maintained within a bioreactor to allow the maturation of the product in preparation for implantation.Specifically,the bioreactor should be designed to mimic the mechanical,electrochemical and biochemical environment that the product will be exposed to in vivo.Real-time monitoring of the functional capacity of tissue-engineered products during manufacturing is a critical component of the quality management process.The present review provides a brief overview of bioreactor engineering considerations.In addition,strategies for bioreactor automation,in-line product monitoring and quality assurance are discussed.

Kidney regeneration: Where we are and future perspectives

In 2012,about 16487 people received kidney transplants in the United States,whereas 95022 candidates were on the waiting list by the end of the year.Despite advances in renal transplant immunology,approximately 40%of recipients will die or lose graft within10 years.The limitations of current therapies for renal failure have led researchers to explore the development of modalities that could improve,restore,or replace the renal function.The aim of this paper is to describe a reasonable approach for kidney regeneration and review the current literature regarding cell sources and mechanisms to develop a bioengineering kidney.Due to kidneys peculiar anatomy,extracellular matrix based scaffolds are rational starting point for their regeneration.The perfusion of detergents through the kidney vasculature is an efficient method for delivering decellularizing agents to cells and for removing of cellular material from the tissue.Many efforts have focused on the search of a reliable cell source to provide enrichment for achieving stable renal cell systems.For an efficient bioengineered kidney,these cells must be attached to the organ and then maturated into the bioractors,which simulates the human body environment.A functional bioengineered kidney is still a big challenge for scientists.In the last ten years we have got many improvements on the field of solid organ regeneration;however,we are still far away from the main target.Currently,regenerative centers worldwide have been striving to find feasible strategies to develop bioengineered kidneys.Cell-scaffold technology gives hope to end-stage renal disease patients who struggle with morbidity and mortality due to extended periods on dialysis or immunosupression.The potential of bioengineered organ is to provide a reliable source of organs,which can be refunctionalized and transplanted.

Skin bioprinting:the future of burn wound reconstruction?

Burns are a significant cause of trauma,and over the years,the focus of patient care has shifted from just survival to facilitation of improved functional outcomes.Typically,burn treatment,especially in the case of extensive burn injuries,involves surgical excision of injured skin and reconstruction of the burn injury with the aid of skin substitutes.Conventional skin substitutes do not contain all skin cell types and do not facilitate recapitulation of native skin physiology.Three-dimensional(3D)bioprinting for reconstruction of burn injuries involves layer-by-layer deposition of cells along with scaffolding materials over the injured areas.Skin bioprinting can be done either in situ or in vitro.Both these approaches are similar except for the site of printing and tissue maturation.There are technological and regulatory challenges that need to be overcome for clinical translation of bioprinted skin for burn reconstruction.However,the use of bioprinting for skin reconstruction following burns is promising;bioprinting will enable accurate placement of cell types and precise and reproducible fabrication of constructs to replace the injured or damaged sites.Overall,3D bioprinting is a very transformative technology,and its use for wound reconstruction will lead to a paradigm shift in patient outcomes.In this review,we aim to introduce bioprinting,the different stages involved,in vitro and in vivo skin bioprinting,and the various clinical and regulatory challenges in adoption of this technology.