Inflammation in tissue engineering: The Janus between engraftment and rejection

Abstract

Tissue engineering (TE) for tissue and organ regeneration or replacement is generally performed with scaffold implants, which provide structural and molecular support to in vitro seeded or in vivo recruited cells. TE implants elicit the host immune response, often resulting in engraftment impediment or rejection. Besides this negative effect, however, the immune system components also yield a positive influence on stem cell recruitment and differentiation, allowing tissue regeneration and healing. Thus, a balanced cooperation between proinflammatory and proresolution players of the immune response is an essential element of implant success. In this context, macrophage plasticity plays a fundamental role. Therefore modulating the immune response, instead of immune suppressing the host, might be the best way to successfully implant TE tissues or organs. In particular, it is becoming evident that the scaffold, immune, and stem cells are linked by a three-way interaction, and many efforts are being made for scaffold-appropriate design and functionalization in order to drive the inflammation process toward regeneration, vascularization, and implant success. This review discusses current and potential strategies for inflammation modulation to aid engraftment and regeneration, supporting the concept that quality, and not quantity, of inflammation might influence implant success.Keywords: Implant r Macrophage r Scaffold r Stem cell r Tissue engineering IntroductionTissue engineering and regenerative medicine (TERM) applications intend to improve or replace compromised biological functions by stimulating the intrinsic regenerative capacity of the body or even by replacing damaged tissues and organs. To provide the structure and attachment surface to drive tissue regeneration, Correspondence: Prof. Laura Teodori e-mail: laura.teodori@enea.it scaffolds of synthetic, or natural origin, which may or may not be seeded with stem cells, are constructed and implanted into the human body to foster regeneration. Scaffolds are particularly important for the replacement of a variety of tissues such as skin, bone, and muscle tissue (e.g. maxillofacial reconstructions, heart valves, and vessels) [1]. Depending on the type of tissue to be * These authors contributed equally to this work.C 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu Eur. J. Immunol. 2015. 45: 3222-3236 HIGHLIGHTS 3223replaced, different types of scaffolds are suitable to support regeneration and engraftment. This review provides a general view on the different biomaterials/scaffold types and properties; however the available literature on the matter extensively reports the most frequently used types of scaffolds and their application [2,3]. Although TERM research greatly advanced in recent years, one major challenge is the immune response elicited by the implant, which often leads to a precocious reabsorption, to fibrosis of the implant, and/or to implant rejection, leading to eventual failure of the intervention [4]. To ensure the success of t...

Control of angiogenesis and host response by modulating the cell adhesion properties of an Elastin-Like Recombinamer-based hydrogel

“…Scaffold architecture is also reported to significantly affect the host immune response. In particular, highly porous scaffolds seemed to stimulate less severe immune responses to biomaterials probably because they allowed cell infiltrate and the scaffold digestion [48]. In our study, we found that the open structure and the functionalization allowed an increasing infiltration of host cells with time in vivo and a resorption of the hydrogel without generating a severe foreign body reaction.…”

“…Engineered tissues elicit the host immune response upon implantation and the balance between inflammation and pro-resolution is essential to determine their rejection or successful engraftment [48]. Therefore, successful tissue and organ regeneration/repair based on engineered construct approaches highly depends on the vascularization dynamics of the implant and the immune response and both need to be tailored to the specific application (e.g.…”

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