Biodegradable poly(D,L‐lactide) coating of implants for continuous release of growth factors

Abstract

Local application of growth factors like insulin like growth factor-I (IGF-I) and transforming growth factor-beta 1 (TGF-beta1) from a biodegradable thin layer of poly(D,L-lactide) (PDLLA) coated implants could stimulate fracture healing. A new "cold coating technique" for metallic implants was established to produce a biodegradable coating with a high mechanical stability that provides a continuous release of incorporated growth factors. The properties of this bioactive coating were investigated in vitro and in vivo. Scanning electron microscope analysis revealed a coating thickness of in average 14.8 microm on titanium and 10.7 microm on steel wires. Intramedullary implantation and extraction experiments depicted a loss of PDLLA coating from titanium and steel implants of less than 5%. After explantation of the implants, the coating displayed a complete and regular layer without any defects of PDLLA uncovering the metallic surface. Smear tests demonstrate that the coating can be performed under sterile conditions. The PDLLA depicted a reduction of about 8% within 6 weeks in vitro and in vivo. The growth factors were incorporated in a stable form and demonstrated a loss of stability of less than 3% within 42 days and less than 5% within one year. In an elution experiment, 54% IGF-I and 48% TGF-beta1 were released within the first 48 h. After 42 days, 76% of IGF-I and 71% of TGF-beta1 were detected in the elution fluid by ELISA. Comparable results were obtained in the in vivo experiments after 42 days.

Locally delivered TGF-β1 and IGF-1 enhance the fixation of titanium implants: A study in dogs

“…Several studies have demonstrated that PDLLA is a suitable delivery vehicle for growth factors in both fracture healing and spinal fusion studies (Schmidmaier et al 2001a,b). In a saline dilution model using the same coating process, PDLLA released approximately half of the growth factors within 48 h and another 25% within 6 weeks (Schmidmaier et al 2001b). Although the in vivo release pattern may be accelerated, we can expect that the growth factors were indeed released to the surrounding gap.…”

“…The embedded specimens with the implant in situ were randomly rotated around the vertical axis of the implant. In the central part of implants, 4 serial sections of 15-20 µm were produced using a Leiden microtome (Leiden, Holland) (Overgaard et al 2000, Schmidmaier et al 2001b) Histomorphometry was performed in a blinded fashion using an image analysis system (CAST-Grid; Olympus, Denmark). Quantification of tissue was performed using stereological principles (Gundersen et al 1988).…”

“…Applications used in other studies for local growth factor delivery have included growth factor adsorption to calcium phosphates, mixtures of calcium phosphates and collagen, collagen sponges, hydrogels, immobilization of growth factors on implant surfaces, and use of various polymers , Vehof et al 2002, Barboza et al 2004, Rose et al 2004, Ito et al 2005. Lactide-based polymers such as poly (D, L-Lactide) (PDLLA) have been used clinically for decades as material for screws and plates, and PDLLA has been used successfully as a drug carrier (Nicolas et al 1994, Schmidmaier et al 2001b, Rose et al 2004. A few cases of inflammatory reactions have been seen, but only with bulky-design PDLLA implants (Bostman 1998).…”

Long-term effects of local growth factor (IGF-I and TGF-$beta;1) treatment on fracture healing*1A safety study for using growth factors

“…The properties of the PDLLA coating and the release characteristics of the incorporated growth factors were described previously [22]. Briefly, approximately 50% of the incorporated growth factors were released within the first 48 h followed by a sustained release of a further 30% over the next 40 days.…”

Dose-dependent effects of combined IGF-I and TGF-β1 application in a sheep cervical spine fusion model

“…The properties of the PDLLA coating and the coating technique have been described previously [17,48]. In groups 2-4, recombinant human insulin like growth factor I (IGF-I, R&D Systems) was incorporated in the PDLLA coating at a level of 2.5, 5 and 10% w/w for group 1, group 2 and group 3 respectively, and recombinant human transforming growth factor-beta 1 (TGF-β1, R&D Systems) was incorporated at a level of 0.5, 1 and 2% w/w) respectively.…”