Electrospun PLLA Nanofiber Scaffolds and Their Use in Combination with BMP-2 for Reconstruction of Bone Defects

Abstract

IntroductionAdequate migration and differentiation of mesenchymal stem cells is essential for regeneration of large bone defects. To achieve this, modern graft materials are becoming increasingly important. Among them, electrospun nanofiber scaffolds are a promising approach, because of their high physical porosity and potential to mimic the extracellular matrix (ECM).Materials and MethodsThe objective of the present study was to examine the impact of electrospun PLLA nanofiber scaffolds on bone formation in vivo, using a critical size rat calvarial defect model. In addition we analyzed whether direct incorporation of bone morphogenetic protein 2 (BMP-2) into nanofibers could enhance the osteoinductivity of the scaffolds. Two critical size calvarial defects (5 mm) were created in the parietal bones of adult male Sprague-Dawley rats. Defects were either (1) left unfilled, or treated with (2) bovine spongiosa, (3) PLLA scaffolds alone or (4) PLLA/BMP-2 scaffolds. Cranial CT-scans were taken at fixed intervals in vivo. Specimens obtained after euthanasia were processed for histology, histomorphometry and immunostaining (Osteocalcin, BMP-2 and Smad5).ResultsPLLA scaffolds were well colonized with cells after implantation, but only showed marginal ossification. PLLA/BMP-2 scaffolds showed much better bone regeneration and several ossification foci were observed throughout the defect. PLLA/BMP-2 scaffolds also stimulated significantly faster bone regeneration during the first eight weeks compared to bovine spongiosa. However, no significant differences between these two scaffolds could be observed after twelve weeks. Expression of osteogenic marker proteins in PLLA/BMP-2 scaffolds continuously increased throughout the observation period. After twelve weeks osteocalcin, BMP-2 and Smad5 were all significantly higher in the PLLA/BMP-2 group than in all other groups.ConclusionElectrospun PLLA nanofibers facilitate colonization of bone defects, while their use in combination with BMP-2 also increases bone regeneration in vivo and thus combines osteoconductivity of the scaffold with the ability to maintain an adequate osteogenic stimulus.

Electrospun adherent–antiadherent bilayered membranes based on cross-linked hyaluronic acid for advanced tissue engineering applications

“…This led us to combine the HA mat with another polymer into a two-layer membrane. Here, HA has been electrospun onto previously obtained mats of poly(L-lactic acid) (PLLA), which possesses a great electrospinning processability [17], proper mechanical behavior and manipulability, and is a noncytotoxic and biodegradable FDA approved polymer [18]. Another reason to combine electrospinning of HA with PLLA is that the latter has proved to be easily colonized in vitro by different cells types, whereas HA has non-adherent properties [19] and has already been tested in clinical trials to prevent surgical adhesions [20].…”

The effects of poly L-lactic acid nanofiber scaffold on mouse spermatogonial stem cell culture

“…22 Recently, many electrospun nanofibrillar surfaces have been used for cell culture. [23][24][25][26] Poly L-lactic acid (PLLA) is one of the most promising biodegradable, biocompatible, and US Food and Drug Administration-approved polymers 27 and can easily be electrospun to form a 3D non-woven network. 28,29 To date, the proliferation of muscle-derived stem cells 30 and the differentiation of hepatic cells from human mesenchymal stem cells 31 have been established on PLLA.…”

Nanotechnology in orthopedics

“…PLLA has been used to delivery bone morphogenetic protein (BMP), which has in turn improved the time of closing for certain large bone defects. 27 Nanophase drug delivery is being investigated for its potential application to TJR. In one study by Li et al, a nanofilm made of a biodegradeable polypeptide was used to deliver cefazolin; the results of this study demonstrated that nanoscale drug delivery for TJR may help decrease risk of infection in addition to improving osteoblast recruitment and bone growth.…”