High-throughput drug screening models of mature adipose tissues which replicate the physiology of patients’Body Mass Index(BMI)

Obesity is a complex and incompletely understood disease,but current drug screening strategies mostly rely on immature in vitro adipose models which cannot recapitulate it properly.To address this issue,we developed a statistically validated high-throughput screening model by seeding human mature adipocytes from patients,encapsulated in physiological collagen microfibers.These drop tissues ensured the maintenance of adipocyte viability and functionality for controlling glucose and fatty acids uptake,as well as glycerol release.As such,patients’BMI and insulin sensitivity displayed a strong inverse correlation:the healthy adipocytes were associated with the highest insulin-induced glucose uptake,while insulin resistance was confirmed in the underweight and severely obese adipocytes.Insulin sensitivity recovery was possible with two type 2 diabetes treatments,rosiglitazone and melatonin.Finally,the addition of blood vasculature to the model seemed to more accurately recapitulate the in vivo physiology,with particular respect to leptin secretion metabolism.

Bioprinted Vascularized Mature Adipose Tissue with Collagen Microfibers for Soft Tissue Regeneration

The development of soft tissue regeneration has recently gained importance due to safety concerns about artificial breast implants.Current autologous fat graft implantations can result in up to 90%of volume loss in long-term outcomes due to their limited revascularization.Adipose tissue has a highly vascularized structure which enables its proper homeostasis as well as its endocrine function.Mature adipocytes surrounded by a dense vascular network are the specific features required for efficient regeneration of the adipose tissue to perform host anastomosis after its implantation.Recently,bioprinting has been introduced as a promising solution to recreate in vitro this architecture in large-scale tissues.However,the in vitro induction of both the angiogenesis and adipogenesis differentiations from stem cells yields limited maturation states for these two pathways.To overcome these issues,we report a novel method for obtaining a fully vascularized adipose tissue reconstruction using supporting bath bioprinting.For the first time,directly isolated mature adipocytes encapsulated in a bioink containing physiological collagen microfibers(CMF)were bioprinted in a gellan gum supporting bath.These multilayered bioprinted tissues retained high viability even after 7 days of culture.Moreover,the functionality was also confirmed by the maintenance of fatty acid uptake from mature adipocytes.Therefore,this method of constructing fully functional adipose tissue regeneration holds promise for future clinical applications.