Strut size and surface area effects on long-term in vivo degradation in computer designed poly(L-lactic acid) three-dimensional porous scaffolds.

Current developments in computer-aided design (CAD) and solid free-form fabrication (SFF) techniques enable fabrication of scaffolds with precisely designed architectures and mechanical properties. The present study demonstrates the effect of precisely designed three-dimensional scaffold architectures on in vivo degradation. Specifically, three types of porous poly(L-lactic acid) (PLLA) scaffolds with variable pore sizes, strut sizes, porosities, and surface areas fabricated by indirect SFF. In addition, one experimental group of PLLA solid cylinders was fabricated. The scaffolds and cylinders were subcutaneously implanted into mice for 6, 12 and 21 weeks. The solid cylinders exhibited a faster percentage mass loss than all porous scaffolds. Among the porous scaffolds the group with the largest strut size lost percentage mass faster than the other two groups. Strong correlations between surface area and percentage mass loss were found at 12 (R(2)=0.681) and 21 (R(2)=0.671) weeks. Scaffold porosity, however, was not significantly correlated with degradation rate. Changes in molecular weight and crystallinity also resulted in changes in the chemical structures due to degradation, and the solid cylinders had faster crystallization due to more advanced degradation than the porous scaffolds. Scaffold compressive moduli decreased with degradation, but the resulting modulus was still within the lower range of human trabecular bone even after 21 weeks. The loss in compressive moduli, however, was a complex function of both degradation and the initial scaffold architecture. This study suggests that CAD and fabrication, within a given material, can significantly influence scaffold degradation profiles.

[1]  Colleen L Flanagan,et al.  Experimental and computational characterization of designed and fabricated 50:50 PLGA porous scaffolds for human trabecular bone applications , 2010, Journal of materials science. Materials in medicine.

[2]  Chad Johnson,et al.  The effect of scaffold degradation rate on three-dimensional cell growth and angiogenesis. , 2004, Biomaterials.

[3]  Stephen E. Feinberg,et al.  An image-based approach for designing and manufacturing craniofacial scaffolds. , 2000, International journal of oral and maxillofacial surgery.

[4]  Moe R. Lim,et al.  Bioabsorbable interbody spacers. , 2007, The Journal of the American Academy of Orthopaedic Surgeons.

[5]  Dietmar Werner Hutmacher,et al.  The evaluation of a biphasic osteochondral implant coupled with an electrospun membrane in a large animal model. , 2009, Tissue engineering. Part A.

[6]  Jia-cong Shen,et al.  In vitro and in vivo degradability and cytocompatibility of poly(l-lactic acid) scaffold fabricated by a gelatin particle leaching method. , 2007, Acta biomaterialia.

[7]  L. Nicolais,et al.  Influence of crystal and amorphous phase morphology on hydrolytic degradation of PLLA subjected to different processing conditions , 2001 .

[8]  S. Hollister Porous scaffold design for tissue engineering , 2005, Nature materials.

[9]  R Langer,et al.  In vitro and in vivo degradation of porous poly(DL-lactic-co-glycolic acid) foams. , 2000, Biomaterials.

[10]  Dietmar W Hutmacher,et al.  Scaffold-based tissue engineering: rationale for computer-aided design and solid free-form fabrication systems. , 2004, Trends in biotechnology.

[11]  J F Orr,et al.  Degradation of poly-L-lactide. Part 1: in vitro and in vivo physiological temperature degradation , 2004, Proceedings of the Institution of Mechanical Engineers. Part H, Journal of engineering in medicine.

[12]  J F Orr,et al.  Processing, annealing and sterilisation of poly-L-lactide. , 2004, Biomaterials.

[13]  M. Vert,et al.  In vitro and in vivo degradation of lactic acid-based interference screws used in cruciate ligament reconstruction. , 1999, International journal of biological macromolecules.

[14]  Colleen L Flanagan,et al.  Bone tissue engineering using polycaprolactone scaffolds fabricated via selective laser sintering. , 2005, Biomaterials.

[15]  Yubo Fan,et al.  Effect of Cyclic Loading on In Vitro Degradation of Poly(L-lactide-co-glycolide) Scaffolds , 2010, Journal of biomaterials science. Polymer edition.

[16]  J C Middleton,et al.  Synthetic biodegradable polymers as orthopedic devices. , 2000, Biomaterials.

[17]  Robert C. Breithaupt,et al.  The influence of stereolithographic scaffold architecture and composition on osteogenic signal expression with rat bone marrow stromal cells. , 2011, Biomaterials.

[18]  Linbo Wu,et al.  In vitro degradation of three-dimensional porous poly(D,L-lactide-co-glycolide) scaffolds for tissue engineering. , 2004, Biomaterials.

[19]  F. Cui,et al.  In vitro and in vivo degradation of mineralized collagen-based composite scaffold: nanohydroxyapatite/collagen/poly(L-lactide). , 2004, Tissue engineering.

[20]  Linbo Wu,et al.  Effects of porosity and pore size on in vitro degradation of three-dimensional porous poly(D,L-lactide-co-glycolide) scaffolds for tissue engineering. , 2005, Journal of biomedical materials research. Part A.

[21]  Robert Langer,et al.  Size and temperature effects on poly(lactic-co-glycolic acid) degradation and microreservoir device performance. , 2005, Biomaterials.

[22]  J. A. Cooper,et al.  Fabrication and characterization of six electrospun poly(alpha-hydroxy ester)-based fibrous scaffolds for tissue engineering applications. , 2006, Acta biomaterialia.

[23]  Clemens A van Blitterswijk,et al.  Effects of the architecture of tissue engineering scaffolds on cell seeding and culturing. , 2010, Acta biomaterialia.

[24]  Michael J Yaszemski,et al.  Poly(propylene fumarate) bone tissue engineering scaffold fabrication using stereolithography: effects of resin formulations and laser parameters. , 2007, Biomacromolecules.

[25]  Jason A Burdick,et al.  An initial investigation of photocurable three-dimensional lactic acid based scaffolds in a critical-sized cranial defect. , 2003, Biomaterials.

[26]  C. Chen,et al.  Preparation and characterization of biodegradable PLA polymeric blends. , 2003, Biomaterials.

[27]  J. Pagkalos,et al.  Bioabsorbable materials in orthopaedics. , 2007, Acta orthopaedica Belgica.

[28]  J. Vacanti,et al.  In vitro degradation of porous poly(L-lactic acid) foams. , 2000, Biomaterials.

[29]  A. Boccaccini,et al.  Biodegradable and bioactive porous polymer/inorganic composite scaffolds for bone tissue engineering. , 2006, Biomaterials.

[30]  Michel Vert,et al.  Structure-property relationships in the case of the degradation of massive poly(α-hydroxy acids) in aqueous media , 1990 .

[31]  Dietmar W. Hutmacher,et al.  Scaffold design and fabrication technologies for engineering tissues — state of the art and future perspectives , 2001, Journal of biomaterials science. Polymer edition.

[32]  S. Hollister,et al.  Effects of designed PLLA and 50:50 PLGA scaffold architectures on bone formation in vivo , 2013, Journal of tissue engineering and regenerative medicine.

[33]  A. Albertsson,et al.  Porosity and pore size regulate the degradation product profile of polylactide. , 2011, Biomacromolecules.

[34]  C. Zavaglia,et al.  Porous and dense poly(L-lactic acid) and poly(D,L-lactic acid-co-glycolic acid) scaffolds: In vitro degradation in culture medium and osteoblasts culture , 2004, Journal of materials science. Materials in medicine.

[35]  Dietmar Werner Hutmacher,et al.  State of the art and future directions of scaffold‐based bone engineering from a biomaterials perspective , 2007, Journal of tissue engineering and regenerative medicine.

[36]  M J Yaszemski,et al.  Ectopic bone formation by marrow stromal osteoblast transplantation using poly(DL-lactic-co-glycolic acid) foams implanted into the rat mesentery. , 1997, Journal of biomedical materials research.

[37]  Suming Li,et al.  Hydrolytic degradation characteristics of aliphatic polyesters derived from lactic and glycolic acids. , 1999 .

[38]  Scott J Hollister,et al.  The pore size of polycaprolactone scaffolds has limited influence on bone regeneration in an in vivo model. , 2010, Journal of biomedical materials research. Part A.

[39]  Peter X Ma,et al.  The effect of surface area on the degradation rate of nano-fibrous poly(L-lactic acid) foams. , 2006, Biomaterials.

[40]  Younan Xia,et al.  Three-dimensional scaffolds for tissue engineering: the importance of uniformity in pore size and structure. , 2010, Langmuir : the ACS journal of surfaces and colloids.

[41]  E. Pamuła,et al.  In vitro and in vivo degradation of poly(l-lactide-co-glycolide) films and scaffolds , 2008, Journal of materials science. Materials in medicine.

[42]  J. Mühling,et al.  Poly(L-lactide): a long-term degradation study in vivo. Part II: Physico-mechanical behaviour of implants. , 1993, Biomaterials.

[43]  C. M. Agrawal,et al.  Fundamentals of biomechanics in tissue engineering of bone. , 2000, Tissue engineering.

[44]  M. Shive,et al.  Biodegradation and biocompatibility of PLA and PLGA microspheres , 1997 .

[45]  W C de Bruijn,et al.  Late degradation tissue response to poly(L-lactide) bone plates and screws. , 1995, Biomaterials.

[46]  R. Giardino,et al.  Resorbable Device for Fracture Fixation: In Vivo Degradation and Mechanical Behaviour , 1995, International Journal of Artificial Organs.

[47]  Wei Sun,et al.  Computer‐aided tissue engineering: application to biomimetic modelling and design of tissue scaffolds , 2004, Biotechnology and applied biochemistry.

[48]  N. Ashammakhi,et al.  The use of bioabsorbable osteofixation devices in craniomaxillofacial surgery. , 2002, Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics.

[49]  C. M. Agrawal,et al.  Effects of fluid flow on the in vitro degradation kinetics of biodegradable scaffolds for tissue engineering. , 2000, Biomaterials.

[50]  R. Adhikari,et al.  Biodegradable synthetic polymers for tissue engineering. , 2003, European cells & materials.

[51]  Sangwon Chung,et al.  Hierarchical starch‐based fibrous scaffold for bone tissue engineering applications , 2009, Journal of tissue engineering and regenerative medicine.

[52]  E. D. Rekow,et al.  Performance of degradable composite bone repair products made via three-dimensional fabrication techniques. , 2003, Journal of biomedical materials research. Part A.

[53]  W. Dockery,et al.  Long-term absorption of poly-L-lactic Acid interference screws. , 2006, Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association.

[54]  Michael J Yaszemski,et al.  Enhanced cell ingrowth and proliferation through three-dimensional nanocomposite scaffolds with controlled pore structures. , 2010, Biomacromolecules.

[55]  Dong-Woo Cho,et al.  Effect of Thermal Degradation of SFF-Based PLGA Scaffolds Fabricated Using a Multi-head Deposition System Followed by Change of Cell Growth Rate , 2010, Journal of biomaterials science. Polymer edition.

[56]  Joo L. Ong,et al.  Diffusion in Musculoskeletal Tissue Engineering Scaffolds: Design Issues Related to Porosity, Permeability, Architecture, and Nutrient Mixing , 2004, Annals of Biomedical Engineering.

[57]  R. Guidoin,et al.  Removing fresh tissue from explanted polyurethane prostheses: which approach facilitates physico-chemical analysis? , 1995, Biomaterials.

[58]  Suming Li,et al.  Hydrolytic degradation of devices based on poly(DL-lactic acid) size-dependence. , 1995, Biomaterials.

[59]  Dong-Woo Cho,et al.  Surface modification with fibrin/hyaluronic acid hydrogel on solid-free form-based scaffolds followed by BMP-2 loading to enhance bone regeneration. , 2011, Bone.

[60]  P H Krebsbach,et al.  Indirect solid free form fabrication of local and global porous, biomimetic and composite 3D polymer-ceramic scaffolds. , 2003, Biomaterials.

[61]  Y. Wan,et al.  Porous-conductive chitosan scaffolds for tissue engineering II. in vitro and in vivo degradation , 2005, Journal of materials science. Materials in medicine.

[62]  G. Yin,et al.  A study on the in vitro degradation properties of poly(L-lactic acid)/beta-tricalcuim phosphate (PLLA/beta-TCP) scaffold under dynamic loading. , 2009, Medical engineering & physics.

[63]  Joseph W Freeman,et al.  Anterior cruciate ligament regeneration using braided biodegradable scaffolds: in vitro optimization studies. , 2005, Biomaterials.

[64]  R L Reis,et al.  Starch–poly(ε‐caprolactone) and starch–poly(lactic acid) fibre‐mesh scaffolds for bone tissue engineering applications: structure, mechanical properties and degradation behaviour , 2008, Journal of tissue engineering and regenerative medicine.