Use of Nanoparticles in Tissue Engineering and Regenerative Medicine

Advances in nanoparticle (NP) production and demand for control over nanoscale systems have had significant impact on tissue engineering and regenerative medicine (TERM). NPs with low toxicity, contrasting agent properties, tailorable characteristics, targeted/stimuli-response delivery potential, and precise control over behavior (via external stimuli such as magnetic fields) have made it possible their use for improving engineered tissues and overcoming obstacles in TERM. Functional tissue and organ replacements require a high degree of spatial and temporal control over the biological events and also their real-time monitoring. Presentation and local delivery of bioactive (growth factors, chemokines, inhibitors, cytokines, genes etc.) and contrast agents in a controlled manner are important implements to exert control over and monitor the engineered tissues. This need resulted in utilization of NP based systems in tissue engineering scaffolds for delivery of multiple growth factors, for providing contrast for imaging and also for controlling properties of the scaffolds. Depending on the application, materials, as polymers, metals, ceramics and their different composites can be utilized for production of NPs. In this review, we will cover the use of NP systems in TERM and also provide an outlook for future potential use of such systems

Büyüme faktörlü yüklenmiş ipek fibroin/PEGDMA hidrojelleriyle artiküler kıkırdak doku mühendisliği.

The aim of this study was to develop bFGF and TGF-β1 loaded polymeric nanoparticles (PNPs) and dental pulp stem cells (DPSCs) containing dimethacrylated poly(ethylene glycol) (PEGDMA)/silk fibroin hydrogels as scaffolds for regeneration of the cartilage tissue. Poly(lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) were prepared with double emulsion-solvent evaporation technique. The effect of different excipients (poly(2-ethyl-2-oxazoline) (PetOx), heparin and Kolliphor P 188) on the entrapment efficiency of growth factors in NPs and release kinetics from PLGA NPs in PBS at 37°C was investigated. For preparation of bFGF and TGF-β1 loaded NPs 0.5% and 1.0% (W/V) heparin excipients have been chosen, respectively. bFGF loaded NPs with 0.5% (W/V) heparin has shown highest cumulative percent release, encapsulation efficiency and loading capacity of 51.39 ± 2.22%, 88.1 ± 0.3% and 8.97 ± 0.34%, respectively and highest cell viability in monolayer study. TGF-β1 loaded PLGA NPs with 1.0% (W/V) as excipient was chosen due to highest cumulative percent release, encapsulation efficiency and loading capacity of 13.28 ± 0.19%, 99.65 ± 0.1%, 9.90 ± 0.10%, respectively and cell viability in monolayer study among all excipient groups. Hydrogels composed of silk fibroin and PEGDMA (PEGDMA (10, 15 and 20%) at different volume ratios (silk fibroin: PEGDMA, 3:1, 1:1, 1:3)) were prepared by crosslinking fibroin with sonication and PEGDMA with vi UV photocrosslinking. Hydrogels with various compressive moduli ranging from 95.70 ± 17.82 kPa to 338.05 ± 38.24 kPa were obtained through changing both concentration of PEGDMA and volume ratio of PEGDMA with 8% silk fibroin. 10% (W/W) NPs addition to hydrogels significantly increased their compressive moduli (p ≤ 0.05). Weight loss of blend hydrogels with highest silk fibroin content was the highest among all groups (89.93 ± 7.95% in 28 days). Highest cell viability was observed in PEG10-SF8(1:1) hydrogel group and this hydrogel composition was chosen for preparing hydrogels containing DPSCs and PLGA NPs. Live/dead assay has shown almost no dead cells and also elongated cells inside hydrogels containing both bFGF and TGF-β1 loaded NPs on 7th day. DNA and GAG amounts of hydrogels containing bFGF and TGF-β1 loaded NPs were significantly higher than hydrogels without NPs, empty NPs, and TGF-β1 loaded or bFGF loaded NPs (p ≤ 0.05), showing synergistically effect of dual release of bFGF and TGF-β over proliferation and chondrogenic differentiation of DPSCs in hydrogels. Overall, we conclude that PEG10-SF8(1:1) hydrogel system containing DPSCs and bFGF and TGF-β1 loaded PLGA NPs hold promise for cartilage tissue engineering.M.S. - Master of Scienc

Use of nanoscale-delivery systems in tissue/organ regeneration

iomaterials for Organ and Tissue Regeneration: New Technologies and Future Prospects examines the use of biomaterials in applications related to artificial tissues and organs. With a strong focus on fundamental and traditional tissue engineering strategies, the book also examines how emerging and enabling technologies are being developed and applied. Sections provide essential information on biomaterial, cell properties and cell types used in organ generation. A section on state-of-the-art in organ regeneration for clinical purposes is followed by a discussion on enabling technologies, such as bioprinting, on chip organ systems and in silico simulations

Kıkırdak Doku Mühendisliğine Yönelik Kontrollü Büyüme Faktör Salım Sistemi İçeren İskele Tasarımı

Bu projenin amacı kıkırdak doku rejenerasyonu için bFGF ve TGF-β1 yüklü polimerik nanoküreler ve ATDC5 hücreleri içeren dimetakrilat polietilen glikol (PEG)/fibroin hidrojel temelli kıkırdaksı doku konstrüktü hazırlamaktır. Büyüme faktörleri poli(laktik asit-ko-glikolik) asit nanokürelerin içine hapsedilme aşamasında biyolojik aktivitelerini kaybetmelerinin engellenmesi ve nanokürelerden salım kinetiklerin kontrol edilmesi için farklı moleküler ağırlıklara (Mw) sahip poli (2-etil-2-oksazolin) (PEtOx) ile birlikte nanokürelere yüklenmesi planlanmaktadır. Literatürde ilk defa PEtOx içeren nanokürelerin büyüme faktörlerinin salım profilleri ve biyoaktiviteleri üzerindeki etkisi incelenecektir. İpek fibroin proteinini ve dimetakrilat PEG oluşturulacak olan hidrojel sonikasyion yöntemi ve UV ile foto-çaprazlanma yöntemi ile hazırlanacaktır. Proje kapsamında hidrojeller içinde hücre çoğalmasını arttıracak bFGF’in naokürelerden salınması ve daha sonra TGF-β1 yüklü nanokürelerden TGF-β1 salımı ile kıkırdak hücrelerin fenotipik özelliklerini ifadesini arttırıcı etkisi (hücre dışı matriks sentezi) ile kıkırdak benzeri konstrükt elde edilmesi amaçlanmaktadır. bFGF ve TGF-β1 ardışık salım etkisi dimetakrilat polietilen glikol (PEG)/fibroin hidrojeller içerisinde projenin diğer yenilikçi yönüdür

Dual growth factor delivery using PLGA nanoparticles in silk fibroin/PEGDMA hydrogels for articular cartilage tissue engineering

Degeneration of articular cartilage due to damages, diseases, or age-related factors can significantly decrease the mobility of the patients. Various tissue engineering approaches which take advantage of stem cells and growth factors in a three-dimensional constructs have been used for reconstructing articular tissue. Proliferative impact of basic fibroblast growth factor (bFGF) and chondrogenic differentiation effect of transforming growth factor-beta 1 (TGF-beta 1) over mesenchymal stem cells have previously been verified. In this study, silk fibroin (SF) and of poly(ethylene glycol) dimethacrylate (PEGDMA) were used to provide a versatile platform for preparing hydrogels with tunable mechanical, swelling and degradation properties through physical and chemical crosslinking as a microenvironment for chondrogenic differentiation in the presence of bFGF and TGF-beta 1 releasing nanoparticles (NPs) for the first time. Scaffolds with compressive moduli ranging from 95.70 +/- 17.82 to 338.05 +/- 38.24 kPa were obtained by changing both concentration PEGDMA and volume ratio of PEGDMA with 8% SF. Highest cell viability was observed in PEGDMA 10%-SF 8% (1:1) [PEG10-SF8(1:1)] hydrogel group. Release of bFGF and TGF-beta 1 within PEG10-SF8(1:1) hydrogels resulted in higher DNA and glycosaminoglycans amounts indicating synergistic effect of dual release over proliferation and chondrogenic differentiation of dental pulp stem cells in hydrogels, respectively. Our results suggested that simultaneous delivery of bFGF and TGF-beta 1 through utilization of PLGA NPs within PEG10-SF8(1:1) hydrogel provided a novel and versatile means for articular cartilage regeneration as they allow for dosage- and site-specific multiple growth factor delivery

Use of Nanoparticles in Tissue Engineering and Regenerative Medicine

Advances in nanoparticle (NP) production and demand for control over nanoscale systems have had significant impact on tissue engineering and regenerative medicine (TERM). NPs with low toxicity, contrasting agent properties, tailorable characteristics, targeted/stimuli-response delivery potential, and precise control over behavior (via external stimuli such as magnetic fields) have made it possible their use for improving engineered tissues and overcoming obstacles in TERM. Functional tissue and organ replacements require a high degree of spatial and temporal control over the biological events and also their real-time monitoring. Presentation and local delivery of bioactive (growth factors, chemokines, inhibitors, cytokines, genes etc.) and contrast agents in a controlled manner are important implements to exert control over and monitor the engineered tissues. This need resulted in utilization of NP based systems in tissue engineering scaffolds for delivery of multiple growth factors, for providing contrast for imaging and also for controlling properties of the scaffolds. Depending on the application, materials, as polymers, metals, ceramics and their different composites can be utilized for production of NPs. In this review, we will cover the use of NP systems in TERM and also provide an outlook for future potential use of such systems