New perspectives in regenerative medicine and surgery: the bioactive composite therapies (BACTs)

Michele L. Zocchi,Andrea Sbarbati,Vincenzo Vindigni,Giamaica Conti,Federico Facchin,Franco Bassetto,Andrea Pagani,Claudia Bonino

doi:10.1007/s00238-021-01874-6

Abstract

Regenerative medicine and surgery is a rapidly expanding branch of translational research in tissue engineering, cellular and molecular biology.To date, the methods to improve cell intake, survival, and isolation need to comply with a complex and still unclear regulatory frame, becoming everyday more restrictive and often limiting the effectiveness and outcome of the therapeutic choices. Thus, the authors developed a novel 360° regenerative strategy based on the synergic action of several new components called the bioactive composite therapies (BACTs) to improve grafted cells intake, and survival in total compliance with the legal and ethical limits of the current regulatory frame.The rationale at the origin of this new technology is based on the evidence that cells need supportive substrate to survive in vitro and this observation, applying the concept of translational medicine, is true also in vivo. Bioactive composite mixtures (BACMs) are tailor-made bioactive mixtures containing several bioactive components that support cells’ survival and induce a regenerative response in vivo by stimulating the recipient site to act as an in situ real bioreactor. Many different tissues have been used in the past for the isolation of cells, molecules, and growth factors, but the adipose tissue and its stromal vascular fraction (SVF) remains the most valuable, abundant, safe, and reliable source of regenerative components and particularly of adipose-derived stems cells (ADSCs). The role of plastic surgeons as the historical experts in all the most advanced techniques for harvesting, manipulating, and grafting adipose tissue is fundamental in this constant process of expansion of regenerative procedures. In this article, we analyze the main causes of cell death and the strategies for preventing it, and we present all the technical steps for preparing the main components of BACMs and the different mixing modalities to obtain the most efficient regenerative action on different clinical and pathological conditions. The second section of this work is dedicated to the logical and sequential evolution from simple bioactive composite grafts (BACGs) that distinguished our initial approach to regenerative medicine, to BACTs where many other fundamental technical steps are analyzed and integrated for supporting and enhancing the most efficient regenerative activity. Level of Evidence: Not gradable

Highlights

Regenerative medicine is today considered the newest and most promising global health pillar based on the clinical application of cell therapy by promoting and stimulatingExtended author information available on the last page of the article the body’s own repair mechanisms [1]
The most important limit of current regenerative approaches is that scientists and medical professionals have the unavoidable obligation to comply with rules, laws, and regulations becoming every day more severe and restrictive
Surgeons and scientists involved in translational technology in regenerative therapies should focus on affordable strategies, allowing their diffuse application in all the settings of treatment, avoiding the utilization of very expensive technologies with minimal improvement of nucleated cell isolation

Summary

Introduction

Extended author information available on the last page of the article the body’s own repair mechanisms [1]. MSCs become functional and establish a local regenerative microenvironment called “niche” for ensuring metabolic and chemotactic exchanges. Specific markers such as NG-2b and CD146 are expressed both on the surface of isolated MSCs and on pericytes, a cell population within the microvascular net [8]. Whereas mechanical stimulation and crushing can be at the origin of shear stress, the inflammatory host and immune response are associated with local and systemic cytokines activation; low nutrient supply and hypoxia are key in several metabolic stress processes while PCD for anoikis, due to ECM separation from cellular components, and apoptosis seems to be sustained by abnormal activity of death-associated protein 3 (DAP3) (Fig. 2, Table 1A)

A Major causes of transplanted cell death

Methods of isolation

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Findings

Conclusions