Mahoney Christopher M, Kelmindi-Doko Arta, Snowden Malik J, Peter Rubin J, Marra Kacey G
Department of Bioengineering, University of Pittsburgh, United States.
Department of Bioengineering, University of Pittsburgh, United States; Department of Plastic Surgery, School of Medicine, University of Pittsburgh, United States; McGowan Institute of Regenerative Medicine, University of Pittsburgh, United States.
Acta Biomater. 2017 Aug;58:26-33. doi: 10.1016/j.actbio.2017.05.046. Epub 2017 May 19.
Hydrogels derived from adipose tissue extracellular matrix (AdECM) have shown potential in the ability to generate new adipose tissue in vivo. To further enhance adipogenesis, a composite adipose derived delivery system (CADDS) containing single- and double-walled dexamethasone encapsulated microspheres (SW and DW Dex MS) has been developed. Previously, our laboratory has published the use of Dex MS as an additive to enhance adipogenesis and angiogenesis in adipose tissue grafts. In the current work, AdECM and CADDS are extensively characterized, in addition to conducting in vitro cell culture analysis. Study results indicate the AdECM used for the CADDS has minimal cellular and lipid content allowing for gelation of its collagen structure under physiological conditions. Adipose-derived stem cell (ASC) culture studies confirmed biocompatibility with the CADDS, and adipogenesis was increased in experimental groups containing the hydrogel scaffold. In vitro studies of AdECM hydrogel containing microspheres demonstrated a controlled release of dexamethasone from SW and DW formulations. The delivery of Dex MS via an injectable hydrogel scaffold combines two biologically responsive components to develop a minimally, invasive, off-the-shelf biomaterial for adipose tissue engineering.
Scientists and doctors have yet to develop an off-the-shelf product for patients with soft tissue defects. Recently, the use of adipose derived extracellular matrix (adECM) to generate new adipose tissue in vivo has shown great promise but individually, adECM still has limitations in terms of volume and consistency. The current work introduces a novel composite off-the-shelf construct comprised of an adECM-based hydrogel and dexamethasone encapsulated microspheres (Dex MS). The hydrogel construct serves not only as an injectable protein-rich scaffold but also a delivery system for the Dex MS for non-invasive application to the defect site. The methods and results presented are a progressive step forward in the field of adipose tissue engineering.
源自脂肪组织细胞外基质（AdECM）的水凝胶在体内生成新脂肪组织的能力方面已显示出潜力。为了进一步增强脂肪生成，已开发出一种包含单层和双层地塞米松包封微球（SW和DW Dex MS）的复合脂肪衍生递送系统（CADDS）。此前，我们实验室已发表了将地塞米松微球用作添加剂以增强脂肪组织移植物中脂肪生成和血管生成的研究。在当前工作中，除了进行体外细胞培养分析外，还对AdECM和CADDS进行了广泛表征。研究结果表明，用于CADDS的AdECM细胞和脂质含量极低，使其胶原结构在生理条件下能够凝胶化。脂肪来源干细胞（ASC）培养研究证实了其与CADDS的生物相容性，并且在含有水凝胶支架的实验组中脂肪生成增加。对含有微球的AdECM水凝胶的体外研究表明，地塞米松从SW和DW制剂中可控释放。通过可注射水凝胶支架递送Dex MS结合了两种生物反应性成分，从而开发出一种用于脂肪组织工程的微创、现成的生物材料。
科学家和医生尚未为软组织缺损患者开发出一种现成的产品。最近，利用脂肪来源细胞外基质（adECM）在体内生成新脂肪组织已显示出巨大潜力，但单独来看，adECM在体积和稠度方面仍存在局限性。当前工作引入了一种新型复合现成构建体，其由基于adECM的水凝胶和地塞米松包封微球（Dex MS）组成。该水凝胶构建体不仅作为一种可注射的富含蛋白质的支架，而且还是Dex MS的递送系统，可用于无创应用于缺损部位。所呈现的方法和结果是脂肪组织工程领域向前迈出的进步一步。
