title: Influence of polymer molecular weight in osteoinductive composites for bone tissue regeneration.
abstract: In bone tissue regeneration, certain polymer and calcium-phosphate-based composites have been reported to enhance some biological surface phenomena, facilitating osteoinduction. Although the crucial role of inorganic fillers in heterotopic bone formation by such materials has been shown, no reports have been published on the potential effects the polymer phase may have. The present work starts from the assumption that the polymer molecular weight regulates the fluid uptake, which determines the hydrolysis rate and the occurrence of biological surface processes. Here, two composites were prepared by extruding two different molecular weight L/D,L-lactide copolymers with calcium phosphate apatite. The lower molecular weight copolymer allowed larger fluid uptake in the composite thereof, which was correlated with a higher capacity to adsorb proteins in vitro. Further, the large fluid absorption led to a quicker composite degradation that generated rougher surfaces and enhanced ion release. Following intramuscular implantation in sheep, only the composite with the lower molecular weight polymer could induce heterotopic bone formation. Besides influencing the biological potential of composites, the molecular weight also regulated their viscoelastic behaviour under cyclic stresses. The results lead to the conclusion that designing biomaterials with appropriate physico-chemical characteristics is crucial for bone tissue regeneration in mechanical load-bearing sites.
authors.affiliation: Xpand Biotechnology BV, Bilthoven, The Netherlands. Electronic address: davide.barbieri@xpand-biotech.com.
authors.forename: Davide
authors.initials: D
authors.lastname: Barbieri
authors.forename: Huipin
authors.initials: H
authors.lastname: Yuan
authors.forename: Xiaoman
authors.initials: X
authors.lastname: Luo
authors.forename: Silvia
authors.initials: S
authors.lastname: Farè
authors.forename: Dirk W
authors.initials: DW
authors.lastname: Grijpma
authors.forename: Joost D
authors.initials: JD
authors.lastname: de Bruijn
mesh_terms: D000327:Adsorption; D000818:Animals; D001031:Apatites / Q000737:chemistry; D001696:Biomechanical Phenomena; D001798:Blood Proteins / Q000378:metabolism; D001826:Body Fluids / Q000737:chemistry; D001861:Bone Regeneration / Q000502:physiology*; D002113:Calcification, Physiologic; D002118:Calcium / Q000032:analysis; D055598:Chemical Phenomena; D055119:Elastic Modulus; D005260:Female; D020007:Implants, Experimental; D008855:Microscopy, Electron, Scanning; D008970:Molecular Weight; D010710:Phosphates / Q000032:analysis; D011108:Polymers / Q000737:chemistry*; D012756:Sheep; D012996:Solutions; D017550:Spectroscopy, Fourier Transform Infrared; D014783:Viscosity; D014961:X-Ray Diffraction
chemical_list: D001031:Apatites; D001798:Blood Proteins; D010710:Phosphates; D011108:Polymers; D012996:Solutions; D002118:Calcium
keywords: Biological surface phenomena; Calcium phosphate/polylactide composite; Mechanical properties; Molecular weight; Osteoinduction