skip to main content
US FlagAn official website of the United States government
dot gov icon
Official websites use .gov
A .gov website belongs to an official government organization in the United States.
https lock icon
Secure .gov websites use HTTPS
A lock ( lock ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.


Title: Industrial‐scale fabrication of an osteogenic and antibacterial PLA/silver‐loaded calcium phosphate composite with significantly reduced cytotoxicity
Abstract In this study, we report an industrial‐scale fabrication method of a multifunctional polymer composite as a scaffold material for bone tissue engineering. This study successfully demonstrated the potential of applying industrial polymer processing technologies to produce specially functionalized tissue engineering scaffolds. With the inclusion of a newly synthesized multifunctional additive, silver‐doped‐calcium phosphate (silver‐CaP), the composite material exhibited excellent osteogenic inducibility of human adipose‐derived stem cells (hASC) and satisfactory antibacterial efficacy againstEscherichia coliandStaphylococcus aureus. Also, relative to previously reported methods of direct loading silver particles into polymeric materials, our composite exhibited significantly reduced silver associated cytotoxicity. The enhanced biocompatibility could be a significant advantage for materials to be used for regenerative medicine applications where clinical safety is a major consideration. The impact of different silver loading methodologies on hASC’ osteogenic differentiation was also studied. Overall, the results of this study indicate a promising alternative approach to produce multifunctional scaffolds at industrial‐scale with higher throughput, lower cost, and enhanced reproducibility. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 900–910, 2019.  more » « less
Award ID(s):
1702841
PAR ID:
10075765
Author(s) / Creator(s):
 ;  ;  
Publisher / Repository:
Wiley Blackwell (John Wiley & Sons)
Date Published:
Journal Name:
Journal of Biomedical Materials Research Part B: Applied Biomaterials
Volume:
107
Issue:
4
ISSN:
1552-4973
Page Range / eLocation ID:
p. 900-910
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. Abstract Osteoarthritis is a degenerative joint disease that limits mobility of the affected joint due to the degradation of articular cartilage and subchondral bone. The limited regenerative capacity of cartilage presents significant challenges when attempting to repair or reverse the effects of cartilage degradation. Tissue engineered medical products are a promising alternative to treat osteochondral degeneration due to their potential to integrate into the patient's existing tissue. The goal of this study was to create a scaffold that would induce site‐specific osteogenic and chondrogenic differentiation of human adipose‐derived stem cells (hASC) to generate a full osteochondral implant. Scaffolds were fabricated using 3D‐bioplotting of biodegradable polycraprolactone (PCL) with either β‐tricalcium phosphate (TCP) or decellularized bovine cartilage extracellular matrix (dECM) to drive site‐specific hASC osteogenesis and chondrogenesis, respectively. PCL‐dECM scaffolds demonstrated elevated matrix deposition and organization in scaffolds seeded with hASC as well as a reduction in collagen I gene expression. 3D‐bioplotted PCL scaffolds with 20% TCP demonstrated elevated calcium deposition, endogenous alkaline phosphatase activity, and osteopontin gene expression. Osteochondral scaffolds comprised of hASC‐seeded 3D‐bioplotted PCL‐TCP, electrospun PCL, and 3D‐bioplotted PCL‐dECM phases were evaluated and demonstrated site‐specific osteochondral tissue characteristics. This technique holds great promise as cartilage morbidity is minimized since autologous cartilage harvest is not required, tissue rejection is minimized via use of an abundant and accessible source of autologous stem cells, and biofabrication techniques allow for a precise, customizable methodology to rapidly produce the scaffold. 
    more » « less
  2. Abstract Non-motile primary cilia are dynamic cellular sensory structures and are expressed in adipose-derived stem cells (ASCs). We have previously shown that primary cilia are involved in chemically-induced osteogenic differentiation of human ASC (hASCs)in vitro. Further, we have reported that 10% cyclic tensile strain (1 Hz, 4 hours/day) enhances hASC osteogenesis. We hypothesize that primary cilia respond to cyclic tensile strain in a lineage dependent manner and that their mechanosensitivity may regulate the dynamics of signaling pathways localized to the cilium. We found that hASC morphology, cilia length and cilia conformation varied in response to culture in complete growth, osteogenic differentiation, or adipogenic differentiation medium, with the longest cilia expressed in adipogenically differentiating cells. Further, we show that cyclic tensile strain both enhances osteogenic differentiation of hASCs while it suppresses adipogenic differentiation as evidenced by upregulation ofRUNX2gene expression and downregulation ofPPARGandIGF-1, respectively. This study demonstrates that hASC primary cilia exhibit mechanosensitivity to cyclic tensile strain and lineage-dependent expression, which may in part regulate signaling pathways localized to the primary cilium during the differentiation process. We highlight the importance of the primary cilium structure in mechanosensing and lineage specification and surmise that this structure may be a novel target in manipulating hASC for in tissue engineering applications. 
    more » « less
  3. There is a growing demand for bone graft substitutes that mimic the extracellular matrix properties of the native bone tissue to enhance stem cell osteogenesis. Composite hydrogels containing human bone allograft particles are particularly interesting due to inherent bioactivity of the allograft tissue. Here, we report a novel photocurable composite hydrogel bioink for bone tissue engineering. Our composite bioink is formulated by incorporating human allograft bone particles in a methacrylated alginate formulation to enhance adult human mesenchymal stem cell (hMSC) osteogenesis. Detailed rheology and printability studies confirm suitability of our composite bioinks for extrusion-based 3D bioprinting technology. In vitro studies reveal high cell viability (~90%) for hMSCs up to 28 days of culture within 3D bioprinted composite scaffolds. When cultured within bioprinted composite scaffolds, hMSCs show significantly enhanced osteogenic differentiation as compared to neat scaffolds based on alkaline phosphatase activity, calcium deposition, and osteocalcin expression. 
    more » « less
  4. Abstract Osteoarthritis (OA) involves the degeneration of articular cartilage and subchondral bone. The capacity of articular cartilage to repair and regenerate is limited. A biodegradable, fibrous scaffold containing zinc oxide (ZnO) was fabricated and evaluated for osteochondral tissue engineering applications. ZnO has shown promise for a variety of biomedical applications but has had limited use in tissue engineering. Composite scaffolds consisted of ZnO nanoparticles embedded in slow degrading, polycaprolactone to allow for dissolution of zinc ions over time. Zinc has well‐known insulin‐mimetic properties and can be beneficial for cartilage and bone regeneration. Fibrous ZnO composite scaffolds, having varying concentrations of 1–10 wt.% ZnO, were fabricated using the electrospinning technique and evaluated for human mesenchymal stem cell (MSC) differentiation along chondrocyte and osteoblast lineages. Slow release of the zinc was observed for all ZnO composite scaffolds. MSC chondrogenic differentiation was promoted on low percentage ZnO composite scaffolds as indicated by the highest collagen type II production and expression of cartilage‐specific genes, while osteogenic differentiation was promoted on high percentage ZnO composite scaffolds as indicated by the highest alkaline phosphatase activity, collagen production, and expression of bone‐specific genes. This study demonstrates the feasibility of ZnO‐containing composites as a potential scaffold for osteochondral tissue engineering. 
    more » « less
  5. The utilization of multifunctional composite materials presents significant advantages in terms of system efficiency, cost-effectiveness, and miniaturization, making them highly valuable for a wide range of industrial applications. One approach to harness the multifunctionality of carbon fiber reinforced polymer (CFRP) is to integrate it with a secondary material to form a hybrid composite. In our previous research, we explored the use of carbonaceous material derived from coconut shells as a sustainable alternative to inorganic fillers, aiming to enhance the out-of-plane mechanical performance of CFRP. In this study, our focus is to investigate the influence of carbonized coconut shell particles on the non-structural properties of CFRP, specifically electromagnetic interference (EMI) shielding, thermal stability, and water absorption resistance. The carbonized material was prepared by thermal processing at 400 °C. Varying proportions of carbonized material, ranging from 1% to 5% by weight, were thoroughly mixed with epoxy resin to form the matrix used for impregnating woven carbon fabric with a volume fraction of 29%. Through measurements of scattering parameters, we found that the hybrid composites with particle loadings up to 3% exhibited EMI shielding effectiveness suitable for industrial applications. Also, incorporating low concentrations of carbonized particle to CFRP enhances the thermal stability of hybrid CFRP composites. However, the inclusion of carbonized particle to CFRP has a complex effect on the glass transition temperature. Even so, the hybrid composite with 2% particle loading exhibits the highest glass transition temperature and lowest damping factor among the tested variations. Furthermore, when subjected to a 7-day water immersion test, hybrid composites with 3% or less amount of carbonized particle showed the least water absorption. The favorable outcome can be attributed to good interfacial bonding at the matrix/fiber interface. Conversely, at higher particle concentrations, aggregation of particles and formation of interfacial and internal pores was observed, ultimately resulting in deteriorated measured properties. The improved non-structural functionalities observed in these biocomposites suggest the potential for a more sustainable and cost-effective alternative to their inorganic-based counterparts. This advancement in multifunctional composites could pave the way for enhanced applications of biocomposites in various industries. 
    more » « less