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Since the first work by Laurencin and colleagues on the development of polymeric electrospinning for biomedical purposes, the use of electrospinning technology has found broad applications in such areas of tissue regeneration and drug delivery. More recently, coaxial electrospinning has emerged as an important technique to develop scaffolds for regenerative engineering incorporated with drug(s). However, the addition of a softer core layer leads to a reduction in mechanical properties. Here, novel robust tripolymeric triaxially electrospun fibrous scaffolds were developed with a polycaprolactone (PCL) (core layer), a 50:50 poly (lactic-co-glycolic acid) (PLGA) (sheath layer) and a gelatin (intermediate layer) with a dual drug delivery capability was developed through modified electrospinning. A sharp increase in elastic modulus after the incorporation of PCL in the core of the triaxial fibers in comparison with uniaxial PLGA (50:50) and coaxial PLGA (50:50) (sheath)-gelatin (core) fibers was observed. Thermal analysis of the fibrous scaffolds revealed an interaction between the core-intermediate and sheath-intermediate layers of the triaxial fibers contributing to the higher tensile modulus. A simultaneous dual release of model small molecule Rhodamine B (RhB) and model protein Fluorescein isothiocynate (FITC) Bovine Serum Albumin (BSA) conjugate incorporated in the sheath and intermediate layers of triaxial fibers was achieved. The tripolymeric, triaxial electrospun systems were seen to be ideal for the support of mesenchymal stem cell growth, as shrinkage of fibers normally found with conventional electrospun systems was minimized. These tripolymeric triaxial electrospun fibers that are biomechanically competent, biocompatible, and capable of dual drug release are designed for regenerative engineering and drug delivery applications.

3D printing, an advent from rapid prototyping technology is emerging as a suitable solution for various regenerative engineering applications. In this study, blended gelatin-sodium alginate 3D printed scaffolds with different pore geometries were developed by altering the spatiotemporal alignment of even layered struts in the scaffolds. A significant difference in compression modulus and osteogenic expression due to the difference in spatiotemporal printing was demonstrated. Pore geometry was found to be more dominant than the compressive modulus of the scaffold in regulating osteogenic gene expression. A shift in pore geometry by at least 45° was critical for significant increase in osteogenic gene expression in MC3T3-E1 cells.

The infrapatellar fat pad (IFP) has until recently been viewed as a densely vascular and innervated intracapsular/extrasynovial tissue with biomechanical roles in the anterior compartment of the knee. Over the last decade, secondary to the proposition that the IFP and synovium function as a single unit, its recognized tight molecular crosstalk with emerging roles in the pathophysiology of joint disease, and the characterization of immune-related resident cells with varying phenotypes (e.g., pro and anti-inflammatory macrophages), this structural complex has gained increasing attention as a potential therapeutic target in patients with various knee pathologies including osteoarthritis (KOA). Furthermore, the description of the presence of mesenchymal stem/stromal cells (MSC) as perivascular cells within the IFP (IFP-MSC), exhibiting immunomodulatory, anti-fibrotic and neutralizing activities over key local mediators, has promoted the IFP as an alternative source of MSC for cell-based therapy protocols. These complementary concepts have supported the growing notion of immune and inflammatory events participating in the pathogenesis of KOA, with the IFP/synovium complex engaging not only in amplifying local pathological responses, but also as a reservoir of potential therapeutic cell-based products. Consequently, the aim of this review is to outline the latest discoveries related with the IFP/synovium complex as both an active participant during KOA initiation and progression thus emerging as a potential target, and a source of therapeutic IFP-MSCs. Finally, we discuss how these notions may help the design of novel treatments for KOA through modulation of local cellular and molecular cascades that ultimately lead to joint destruction.