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A common problem in the design of tissue engineered scaffolds using electrospun scaffolds is the poor cellular infiltration into the structure. To tackle this issue, three approaches to scaffold design using electrospinning were investigated: selective leaching of a water-soluble fiber phase (poly ethylene oxide (PEO) or gelatin), the use of micron-sized fibers as the scaffold, and a combination of micron-sized fibers with codeposition of a hyaluronic acid-derivative hydrogel, Heprasil. These designs were achieved by modifying a conventional electrospinning system with two charged capillaries and a rotating mandrel collector. Three types of scaffolds were fabricated: medical grade poly(epsilon-caprolactone)/collagen (mPCL/Col) cospun with PEO or gelatin, mPCL/Col meshes with micron-sized fibers, and mPCL/Col microfibers cosprayed with Heprasil. All three scaffold types supported attachment and proliferation of human fetal osteoblasts. However, selective leaching only marginally improved cellular infiltration when compared to meshes obtained by conventional electrospinning. Better cell penetration was seen in mPCL/Col microfibers, and this effect was more pronounced when Heprasil regions were present in the structure. Thus, such techniques could be further exploited for the design of cell permeable fibrous meshes for tissue engineering applications.

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Conventional clinical therapies are unable to resolve osteochondral defects adequately; hence, tissue engineering solutions are sought to address the challenge. A biphasic implant that was seeded with mesenchymal stem cells (MSCs) and coupled with an electrospun membrane was evaluated as an alternative. This dual phase construct comprised of a polycaprolactone (PCL) cartilage scaffold and a PCL-tricalcium phosphate osseous matrix. Autologous MSCs were seeded into the entire implant via fibrin and the construct was inserted into critically sized osteochondral defects located at the medial condyle and patellar groove of pigs. The defect was resurfaced with a PCL-collagen electrospun mesh, which served as a substitute for periosteal flap in preventing cell leakage. Controls without either implanted MSCs or resurfacing membrane were included. After 6 months, cartilaginous repair was observed with a low occurrence of fibrocartilage at the medial condyle. Osteochondral repair was promoted and host cartilage degeneration was arrested as shown by superior glycosaminoglycan maintenance. This positive morphological outcome was supported by a higher relative Young's modulus, which indicated functional cartilage restoration. Bone ingrowth and remodeling occurred in all groups, with a higher degree of mineralization in the experimental group. Tissue repair was compromised in the absence of the implanted cells or the resurfacing membrane. Moreover, healing was inferior at the patellar groove when compared with the medial condyle and this was attributed to the native biomechanical features.