New polymers for drug delivery systems in orthopaedics: in vivo biocompatibility evaluation.
The use of biodegradable polymers for drug delivery systems excluded the need for a second operation to remove the carrier. However, the development of an avascular fibrous capsule, reducing drug release, has raised concern about these polymers in terms of tissue-implant reaction. Five novel polymers were evaluated in vivo after implantation in the rat dorsal subcutis and compared to the reference polycaprolactone (PCL). Poly(cyclohexyl-sebacate) (PCS), poly(L-lactide-b-1,5-dioxepan-2-one-b-L-lactide) (PLLA-PDXO-PLLA), two 3-hydroxybutyrate-co-3-hydroxyvalerate copolymers (D400G and D600G), and a poly(organo)phosphazene (POS-PheOEt:Imidazole) specimens were histologically evaluated in terms of the inflammatory tissue thickness and vascular density at 4 and 12 weeks from surgery. The highest values of inflammatory tissue thickness were observed in D600G (P < 0.01), PCS (P < 0.001) and PLLA-PDXO-PLLA (P < 0.001) at 4 weeks, while POP-PheOEt:Imidazole showed the lowest value of inflammatory tissue thickness (P < 0.05) at 12 weeks. D400G, D600G, PLLA-PDXO-PPLA and POP-PheOEt:Imidazole showed higher (P < 0.001) values of vascular density near the implants in comparison to PCL at 4 weeks. Finally, D400G and D600G increased their vessel densities while POP-PheOEt:Imidazole and the synthetic polyester PLLA-PDXO-PLLA presented similar vessel density values during experimental times. These different behaviours to improve neoangiogenesis without severe inflammatory tissue-responses could be further investigated with drugs in order to obtain time-programmable drug delivery systems for musculoskeletal therapy.
Department of Experimental Surgery, Istituti Ortopedici Rizzoli, Via di Barbiano, 1/10, 40136 Bologna, Italy. gianluca.giavaresi@ior.it
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G
Giavaresi
M
M
Tschon
V
V
Borsari
J H
JH
Daly
J J
JJ
Liggat
M
M
Fini
V
V
Bonazzi
A
A
Nicolini
A
A
Carpi
M
M
Morra
C
C
Cassinelli
R
R
Giardino
D000818:Animals; D001672:Biocompatible Materials; D005260:Female; D015918:Infusion Pumps, Implantable; D009985:Orthopedics; D011091:Polyesters; D011108:Polymers; D051381:Rats; D017207:Rats, Sprague-Dawley
D001672:Biocompatible Materials; D011091:Polyesters; D011108:Polymers; C016240:polycaprolactone