Please wait a minute...

Frontiers of Materials Science

Front Mater Sci    2012, Vol. 6 Issue (1) : 47-59     DOI: 10.1007/s11706-012-0154-8
The role of crystallinity on differential attachment/proliferation of osteoblasts and fibroblasts on poly(caprolactone-co-glycolide) polymeric surfaces
Helen CUI1,2(), Patrick J. SINKO2
1. Advanced Technology and Regenerative Medicine (ATRM), LLC, Somerville, NJ 08876, USA; 2. Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA
Download: PDF(712 KB)   HTML
Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks

The objective of the present study is to systematically evaluate the role of polymer crystallinity on fibroblast and osteoblast adhesion and proliferation using a series of poly(caprolactone-co-glycolide) (PCL/PGA) polymers. PCL/PGA polymers were selected since they reflect both highly crystalline and amorphous materials. PCL/PGA polymeric materials were fabricated by compression molding into thin films. Five compositions, from PCL or PGA to intermediate copolymeric compositions of PCL/PGA in ratios of 25:75, 35:65 and 45:55, were studied. Pure PCL and PGA represented the crystalline materials while the copolymers were amorphous. The polymers/copolymers were characterized using DSC to assess crystallinity, contact angle measurement for hydrophobicity, and AFM for nanotopography. The PCL/PGA films demonstrated similar hydrophobicity and nanotopography whereas they differed significantly in crystallinity. Cell adhesion to and proliferation on PCL/PGA films and proliferation studies were performed using osteoblasts and NIH-3T3 fibroblasts. It was observed that highly crystalline and rigid PCL and PGA surfaces were significantly more efficient in supporting fibroblast growth, whereas amorphous/flexible PCL/PGA 35:65 was significantly more efficient in supporting growth of osteoblasts. This study demonstrated that while chemical composition, hydrophobicity and surface roughness of PCL/PGA polymers were held constant, crystallinity and rigidity of PCL/PGA played major roles in determining cell responses.

Keywords crystallinity      attachment      proliferation      osteoblast      fibroblast      PCL-PGA     
Corresponding Authors: CUI Helen,   
Issue Date: 05 March 2012
 Cite this article:   
Helen CUI,Patrick J. SINKO. The role of crystallinity on differential attachment/proliferation of osteoblasts and fibroblasts on poly(caprolactone-co-glycolide) polymeric surfaces[J]. Front Mater Sci, 2012, 6(1): 47-59.
E-mail this article
E-mail Alert
Articles by authors
Helen CUI
Patrick J. SINKO
Fig.1  Effects of copolymeric composition of PCL and PGA on the contact angle of pre- and post-hydration compression molded films. Values given in the figure represent five different measurements on three replicate samples per materials, the error bars are the standard deviations. PCL/PGA films (both wet and dry) are similarly hydrophobic.
SubstrateHydrophobicity and thermal properties pre hydration
θH2O/degree (n=5)ΔHm/(J·g-1) (n=3)Tm/°CΔHc /(J·g-1) (n=3)Tc/°Cxc/%
PCL/PGA 25∶7598.5±1.434209-
PCL/PGA 35∶6597.0±1.220112-
PCL/PGA 45∶5598.3±0.61334a)---
Tab.1  Basic parameters of PCL/PGA polymer substrates pre hydration: hydrophobicity and thermal properties
SubstrateHydrophobicity and thermal properties post hydration for 1 h
θH2O/degree (n=5)ΔHm/(J·g-1) (n=3)Tm/°CΔHc /(J·g-1) (n=3)Tc/°Cxc/%
PCL/PGA 25∶7598.5±2.133202---
PCL/PGA 35∶6597.5±1.021112---
PCL/PGA 45∶5595.5±2.11713---
Tab.2  Basic parameters of PCL/PGA polymer substrates post hydration (1 h): hydrophobicity and thermal properties
Fig.2  Typical DSC thermograms of PCL/PGA films.
Fig.3  Representative DSC thermograms on dry and wet PCL/PGA 35∶65 and PGA copolymeric films. The hydration time is 1 h in water at room temperature. There was no change of PCL/PGA film crystallinity due to hydration.
Fig.4  Representative tapping-mode AFM surface topographic features for PCL/PGA films pre and post hydration: PCL; PGA; PCL/PGA 25∶75; PCL/PGA 35∶65; PCL/PGA 45∶55. Apparent smoothing of the post-hydrated surfaces can be clearly seen from these images. Scale bars represent 20 nm.
Fig.5  The pre- and post-hydration roughness of PCL/PGA films. There was significant decrease in surface roughness for post-hydration films. Roughness was calculated from a 20 μm × 20 μm area from AFM tapping mode measurement. Values given in the figure represent the mean of six measurements and error bars, the standard deviations.
SubstrateNanotopographic feature pre hydrationNanotopographic feature post hydrationFeature change
Surface roughness, (RMS±S.D.)/nm (n=6)Mean height, (Ht±S.D.)/nm (n=6)Surface roughness, (RMS±S.D.)/nm (n=6)Mean height, (Ht±S.D.)/nm (n=6)Roughness change, RMS/nmMean height change/nm
PCL/PGA 25∶7525.47±2.32260.4±46.722.48±2.89275.2±22.12.9915
PCL/PGA 35∶6587.70±7.01313.5±35.421.39±5.77260.4±21.566.3153
PCL/PGA 45∶5540.93±8.3887.2±10.315.77±0.73108.2±14.225.1621
Tab.3  Nanotopographic features and changes of roughness for PCL/PGA polymer substrates
Fig.6  Pre-osteoblast attachment and proliferation on PCL/PGA films at 24, 72 and 168 h. Values given in the figure represent the mean of six different experiments and error bars, the standard deviations. (* = test, <0.05 between PCL/PGA 35∶65 and PCL/PGA 25∶75)
Fig.7  Optical microscopy of osteoblast morphology post seeding on PCL/PGA surface: PCL/PGA 35∶65 at 24 h; PCL/PGA 35∶65 at 72 h; PCL/PGA 35∶65 at 168 h; PCL film at 24 h; TCP at 24 h.
Fig.8  Fibroblast attachment and proliferation on PCL/PGA films at 24 and 72 h. Values given in the figure represent the mean of six different experiments and error bars, the standard deviations.
1 Anderson J M, Rodriguez A, Chang D T. Foreign body reaction to biomaterials. Seminars in Immunology , 2008, 20(2): 86-100
2 Yang X B, Roach H I, Clarke N M, . Human osteoprogenitor growth and differentiation on synthetic biodegradable structures after surface modification. Bone , 2001, 29(6): 523-531
3 Harber G M. Cell-material interactions: fundamental design issues for tissue engineering and clinical considerations. In: Guelcher S A, Hollinger J O, eds. An Introduction to Biomaterials . Boca Raton, FL, USA: CRC Press/Taylor &amp; Francis Group, 2006, 189-210
4 Kalbacova M, Rezek B, Baresova V, . Nanoscale topography of nanocrystalline diamonds promotes differentiation of osteoblasts. Acta Biomaterialia , 2009, 5(8): 3076-3085
5 Biggs D L, Lengsfeld C S, Hybertson B M, . In vitro and in vivo valuation of the effects of PLA microparticle crystallinity on cellular response. Journal of Controlled Release , 2003, 92(1-2): 147-161
6 Degirmenbasi N, Ozkan S, Kalyon D M, . Surface patterning of poly(L-lactide) upon melt processing: In vitro culturing of fibroblasts and osteoblasts on surfaces ranging from highly crystalline with spherulitic protrusions to amorphous with nanoscale indentations. Journal of Biomedical Materials Research Part A , 2009, 88A(1): 94-104
7 Kawamoto N, Mori H, Terano M, . Blood compatibility of polypropylene surfaces in relation to the crystalline-amorphous microstructure. Journal of Biomaterials Science, Polymer Edition , 1997, 8(11): 859-877
8 Park A, Cima L G. In vitro cell response to differences in poly-L-lactide crystallinity. Journal of Biomedical Materials Research , 1996, 31(1): 117-130
9 Wang S, Kempen D H, Yaszemski M J, . The roles of matrix polymer crystallinity and hydroxyapatite nanoparticles in modulating material properties of photo-crosslinked composites and bone marrow stromal cell responses. Biomaterials , 2009, 30(20): 3359-3370
10 Washburn N R, Yamada K M, Simon C G Jr, . High-throughput investigation of osteoblast response to polymer crystallinity: influence of nanometer-scale roughness on proliferation. Biomaterials , 2004, 25(7-8): 1215-1224
11 Winet H, Bao J Y. Comparative bone healing near eroding polylactide-polyglycolide implants of differing crystallinity in rabbit tibial bone chambers. Journal of Biomaterials Science, Polymer Edition , 1997, 8(7): 517-532
12 Wang D, Christensen K, Chawla K, . Isolation and characterization of MC3T3-E1 preosteoblast subclones with distinct in vitro and in vivo differentiation/mineralization potential. Journal of Bone and Mineral Research , 1999, 14(6): 893-903
13 Agrawal C M, Ray R B. Biodegradable polymeric scaffolds for musculoskeletal tissue engineering. Journal of Biomedical Materials Research , 2001, 55(2): 141-150
14 Tiaw K S, Teoh S H, Chen R, . Processing methods of ultrathin poly(?-caprolactone) films for tissue engineering applications. Biomacromolecules , 2007, 8(3): 807-816
15 Cheng Z, Teoh S-H. Surface modification of ultra thin poly (?-caprolactone) films using acrylic acid and collagen. Biomaterials , 2004, 25(11): 1991-2001
16 Bramfeldt H, Vermette P. Enhanced smooth muscle cell adhesion and proliferation on protein-modified polycaprolactone-based copolymers. Journal of Biomedical Materials Research Part A , 2009, 88A(2): 520-530
17 Chung T-W, Wang Y-Z, Huang Y-Y, . Poly (?-caprolactone) grafted with nano-structured chitosan enhances growth of human dermal fibroblasts. Artificial Organs , 2006, 30(1): 35-41
18 Ishaug-Riley S L, Okun L E, Prado G, . Human articular chondrocyte adhesion and proliferation on synthetic biodegradable polymer films. Biomaterials , 1999, 20(23-24): 2245-2256
19 Lee S-H, Kim B-S, Kim S H, . Elastic biodegradable poly(glycolide-co-caprolactone) scaffold for tissue engineering. Journal of Biomedical Materials Research Part A , 2003, 66A(1): 29-37
20 Otten J E, Wiedmann-Al-Ahmad M, Jahnke H, . Bacterial colonization on different suture materials — a potential risk for intraoral dentoalveolar surgery. Journal of Biomedical Materials Research Part B, Applied Biomaterials , 2005, 74B(1): 627-635
21 Kowalczyńska H M, Ko?os R, Nowak-Wyrzykowska M, . Atomic force microscopy evidence for conformational changes of fibronectin adsorbed on unmodified and sulfonated polystyrene surfaces. Journal of Biomedical Materials Research Part A , 2009, 91A(4): 1239-1251
22 Ajami-Henriquez D, Rodríguez M, Sabino M, . Evaluation of cell affinity on poly(L-lactide) and poly(?-caprolactone) blends and on PLLA-b-PCL diblock copolymer surfaces. Journal of Biomedical Materials Research Part A , 2008, 87A(2): 405-417
23 Pelham R J Jr, Wang Y. Cell locomotion and focal adhesions are regulated by substrate flexibility. Proceedings of the National Academy of Sciences of the United States of America , 1997, 94(25): 13661-13665
24 Tzvetkova-Chevolleau T, Stéphanou A, Fuard D, . The motility of normal and cancer cells in response to the combined influence of the substrate rigidity and anisotropic microstructure. Biomaterials , 2008, 29(10): 1541-1551
25 Mo X, Weber H-J, Ramakrishna S. PCL-PGLA composite tubular scaffold preparation and biocompatibility investigation. The International Journal of Artificial Organs , 2006, 29(8): 790-799
26 Pamula E, Dobrzynski P, Szot B, . Cytocompatibility of aliphatic polyesters — In vitro tudy on fibroblasts and macrophages. Journal of Biomedical Materials Research Part A , 2008, 87A(2): 524-535
27 Tsai W B, Chen C H, Chen J F, . The effects of types of degradable polymers on porcine chondrocyte adhesion, proliferation and gene expression. Journal of Materials Science: Materials in Medicine , 2006, 17(4): 337-343
28 Tang Z G, Callaghan J T, Hunt J A. The physical properties and response of osteoblasts to solution cast films of PLGA doped polycaprolactone. Biomaterials , 2005, 26(33): 6618-6624
29 Müller A J, Albuerne J, Marquez L, . Self-nucleation and crystallization kinetics of double crystalline poly(p-dioxanone)-b-poly(?-caprolactone) diblock copolymers. Faraday Discussions , 2005, 128: 231-252
30 Hamley I W, Castelletto V, Castillo R V, . Crystallization in poly(L-lactide)-b-poly(?-caprolactone) double crystalline diblock copolymers: A study using X-ray scattering, differential scanning calorimetry, and polarized optical microscopy. Macromolecules , 2005, 38(2): 463-472
31 Gough J E, Christian P, Scotchford C A, . Craniofacial osteoblast responses to polycaprolactone produced using a novel boron polymerisation technique and potassium fluoride post-treatment. Biomaterials , 2003, 24(27): 4905-4912
Related articles from Frontiers Journals
[1] Dongthanh NGUYEN,Wei WANG,Haibo LONG,Hongqiang RU. Synthesis, characterization and photoactivity of bi-crystalline mesoporous TiO2[J]. Front. Mater. Sci., 2016, 10(1): 23-30.
[2] Yonghui LIU,Jun MA,Shengmin ZHANG. Synthesis and thermal stability of selenium-doped hydroxyapatite with different substitutions[J]. Front. Mater. Sci., 2015, 9(4): 392-396.
[3] Ying DONG,Zhiye QIU,Xiaoyu LIU,Liqiang WANG,Jingxin YANG,Yifei HUANG,Fuzhai CUI. Biomechanical evaluation of different hydroxyapatite coatings on titanium for keratoprosthesis[J]. Front. Mater. Sci., 2015, 9(3): 303-310.
[4] Jin-Ning WANG,Bin PI,Peng WANG,Xue-Feng LI,Hui-Lin YANG,Xue-Song ZHU. Sustained release of Semaphorin 3A from α-tricalcium phosphate based cement composite contributes to osteoblastic differentiation of MC3T3-E1 cells[J]. Front. Mater. Sci., 2015, 9(3): 282-292.
[5] Yongze CAO,Qiang WANG,Guojian LI,Yonghui MA,Jiaojiao DU,Jicheng HE. Effects of different magnetic flux densities on microstructure and magnetic properties of molecular-beam-vapor-deposited nanocrystalline Fe64Ni36 thin films[J]. Front. Mater. Sci., 2015, 9(2): 163-169.
[6] Su-Ju XU, Fu-Zhai CUI, Xiao-Long YU, Xiang-Dong KONG. Glioma cell line proliferation controlled by different chemical functional groups in vitro[J]. Front Mater Sci, 2013, 7(1): 69-75.
[7] Xiao-Long YU, Bin ZHANG, Xiu-Mei WANG, Ying WANG, Lin QIAO, Jin HE, Juan WANG, Shuang-Feng CHEN, In-Seop LEE, Fu-Zhai CUI. Cancer cell proliferation controlled by surface chemistry in its microenvironment[J]. Front Mater Sci, 2011, 5(4): 412-416.
[8] F. WATARI, T. AKASAKA, Xiaoming LI, M. UO, A. YOKOYAMA. Proliferation of osteoblast cells on nanotubes[J]. Front Mater Sci Chin, 2009, 3(2): 169-173.
[9] WANG Xiaoping, WANG Leyun, DU Xuan, CUI Fuzhai, MA Xiao, HUANG Yifei. Fast deposition of hydroxyapatite coating on titanium to modify cell affinity of corneal fibroblast in vitro[J]. Front. Mater. Sci., 2007, 1(4): 410-414.
[10] HU Qinghong, CAI Yurong, SHI Zhongli, YAN Weiqi, TANG Ruikang. Inhibition of proliferation of osteosarcoma by nano calcium phosphates: potential hard tissue repair after tumor extraction[J]. Front. Mater. Sci., 2007, 1(1): 30-34.
Full text