Porous-coated titanium implant impregnated with a biodegradable protein delivery system

Abstract

Tissue ingrowth into porous-coated orthopedic and dental implants is commonly used as a means to achieve long-term fixation of these prostheses. However, the degree of tissue ingrowth is often inadequate and inconsistent. If the pores of these implants are impregnated with a controlled drug release system delivering relevant growth factors, then it might be possible to stimulate more tissue ingrowth. The present study introduces such a system based on biodegradable polymers and investigates its protein release profile and polymer degradation characteristics. Porous coated titanium implants were impregnated with a mixture of a 50%-50% polylactic acid-polyglycolic acid copolymer and a model protein, soybean trypsin inhibitor. Control implants contained only the polymer and no protein. The implants were subjected to hydrolytic degradation in phosphate buffered saline at 37 degrees C for periods of 3, 6, and 11 weeks. The protein release and the mass and molecular weight of the polymer were monitored. The results indicate that the protein is released in three distinct phases and the polymer loses almost all its mass and molecular weight by 11 weeks. There was a significant difference in the polymer degradation characteristics between the control and test implants, which might be the result of some complex polymer-protein interactions.

The influence of BMP-2 and its mode of delivery on the osteoconductivity of implant surfaces during the early phase of osseointegration

“…And more recently, attempts have been made to further promote local bone-formation activity by conferring the implant surfaces with osteoinductive properties, namely, by functionalizing them with an osteogenic agent, such as BMP-2 [21][22][23]. Thus far, these compounds have been generally adsorbed directly onto the implant surface [24][25][26][27], although attempts have been made either to bind them chemically thereto [28][29][30] or to incorporate them into a polymer carrier [31][32][33][34]. Since adsorbed osteogenic molecules bind with low affinity to the metallic surface, they are released rapidly within a physiological milieu, thereby generating high local concentrations, which, by stimulating the expression of noggins, can lead to their unspecific inactivation within a few hours to maximally several days [8].…”

The influence of BMP-2 and its mode of delivery on the osteoconductivity of implant surfaces during the early phase of osseointegration

“…And more recently, attempts have been made to further promote local bone-formation activity by conferring the implant surfaces with osteoinductive properties, namely, by functionalizing them with an osteogenic agent, such as BMP-2 [21][22][23]. Thus far, these compounds have been generally adsorbed directly onto the implant surface [24][25][26][27], although attempts have been made either to bind them chemically thereto [28][29][30] or to incorporate them into a polymer carrier [31][32][33][34]. Since adsorbed osteogenic molecules bind with low affinity to the metallic surface, they are released rapidly within a physiological milieu, thereby generating high local concentrations, which, by stimulating the expression of noggins, can lead to their unspecific inactivation within a few hours to maximally several days [8].…”

Nanotechnology for regenerative medicine

“…Unfortunately, however, many conventional synthetic biodegradable polymers and natural scaffolds investigated to date have shown limited success in bladder tissue regeneration applications due to their poor mechanical stability, adverse tissue and immune responses, etc. (Agrawal et al 1997;Kambic et al 1992). Thus, it is necessary to develop bladder organ replacement design strategies not with conventional biodegradable polymers, but rather with advanced novel biodegradable polymers in which the synthetic material is quickly and efficiently replaced by healthy host tissue.…”

Functional Coatings or Films for Hard-Tissue Applications

“…For some applications, a sustained release of bioactive molecules over a long time is required. To achieve this goal, researchers are attempting to incorporate the bioactive molecules into organic coatings such as collagen [258], poly(D,L-lactide) (PDLLA) [257], poly(lactide-co-glycolide) (PLGA) [259] and ethylene vinyl acetate (EVAc) [260]. Schmidmaier et al [257] used BMP-2 to modify the Titanium Kirschner wires with Poly ( d , l -lactide) as a carrier, aiming at tailoring the implant surface to have a controlled, local release of growth factors.…”

The influence of BMP-2 and its mode of delivery on the osteoconductivity of implant surfaces during the early phase of osseointegration

“…And more recently, attempts have been made to further promote local bone-formation activity by conferring the implant surfaces with osteoinductive properties, namely, by functionalizing them with an osteogenic agent, such as BMP-2 [21][22][23]. Thus far, these compounds have been generally adsorbed directly onto the implant surface [24][25][26][27], although attempts have been made either to bind them chemically thereto [28][29][30] or to incorporate them into a polymer carrier [31][32][33][34]. Since adsorbed osteogenic molecules bind with low affinity to the metallic surface, they are released rapidly within a physiological milieu, thereby generating high local concentrations, which, by stimulating the expression of noggins, can lead to their unspecific inactivation within a few hours to maximally several days [8].…”

Nanotechnology for regenerative medicine

“…Unfortunately, however, many conventional synthetic biodegradable polymers and natural scaffolds investigated to date have shown limited success in bladder tissue regeneration applications due to their poor mechanical stability, adverse tissue and immune responses, etc. (Agrawal et al 1997;Kambic et al 1992). Thus, it is necessary to develop bladder organ replacement design strategies not with conventional biodegradable polymers, but rather with advanced novel biodegradable polymers in which the synthetic material is quickly and efficiently replaced by healthy host tissue.…”

Functional Coatings or Films for Hard-Tissue Applications

“…For some applications, a sustained release of bioactive molecules over a long time is required. To achieve this goal, researchers are attempting to incorporate the bioactive molecules into organic coatings such as collagen [258], poly(D,L-lactide) (PDLLA) [257], poly(lactide-co-glycolide) (PLGA) [259] and ethylene vinyl acetate (EVAc) [260]. Schmidmaier et al [257] used BMP-2 to modify the Titanium Kirschner wires with Poly ( d , l -lactide) as a carrier, aiming at tailoring the implant surface to have a controlled, local release of growth factors.…”

The influence of BMP-2 and its mode of delivery on the osteoconductivity of implant surfaces during the early phase of osseointegration

“…And more recently, attempts have been made to further promote local bone-formation activity by conferring the implant surfaces with osteoinductive properties, namely, by functionalizing them with an osteogenic agent, such as BMP-2 [21][22][23]. Thus far, these compounds have been generally adsorbed directly onto the implant surface [24][25][26][27], although attempts have been made either to bind them chemically thereto [28][29][30] or to incorporate them into a polymer carrier [31][32][33][34]. Since adsorbed osteogenic molecules bind with low affinity to the metallic surface, they are released rapidly within a physiological milieu, thereby generating high local concentrations, which, by stimulating the expression of noggins, can lead to their unspecific inactivation within a few hours to maximally several days [8].…”

Nanotechnology for regenerative medicine

“…Unfortunately, however, many conventional synthetic biodegradable polymers and natural scaffolds investigated to date have shown limited success in bladder tissue regeneration applications due to their poor mechanical stability, adverse tissue and immune responses, etc. (Agrawal et al 1997;Kambic et al 1992). Thus, it is necessary to develop bladder organ replacement design strategies not with conventional biodegradable polymers, but rather with advanced novel biodegradable polymers in which the synthetic material is quickly and efficiently replaced by healthy host tissue.…”

Functional Coatings or Films for Hard-Tissue Applications

“…For some applications, a sustained release of bioactive molecules over a long time is required. To achieve this goal, researchers are attempting to incorporate the bioactive molecules into organic coatings such as collagen [258], poly(D,L-lactide) (PDLLA) [257], poly(lactide-co-glycolide) (PLGA) [259] and ethylene vinyl acetate (EVAc) [260]. Schmidmaier et al [257] used BMP-2 to modify the Titanium Kirschner wires with Poly ( d , l -lactide) as a carrier, aiming at tailoring the implant surface to have a controlled, local release of growth factors.…”