In vivo performance of simvastatin‐loaded electrospun spiral‐wound polycaprolactone scaffolds in reconstruction of cranial bone defects in the rat model

Abstract

Reconstruction of large bone defects is still a major problem. Tissue-engineering approaches have become a focus in regeneration of bone. In particular, critical-sized defects do not ossify spontaneously. The use of electrospinning is attracting increasing attention in the preparation of tissue-engineering scaffolds. Recently, acellular scaffolds carrying bioactive agents have been used as scaffolds in "in situ" tissue engineering for soft and hard tissue repair. Poly(epsilon-caprolactone) (PCL) with two different molecular weights were synthesized, and the blends of these two were electrospun into nonwoven membranes composed of nanofibers/micropores. To stimulate bone formation, an active drug, "simvastatin" was loaded either after the membranes were formed or during electrospinning. The matrices were then spiral-wound to produce scaffolds with 3D-structures having both macro- and microchannels. Eight-millimeter diameter critical size cranial defects were created in rats. Scaffolds with or without simvastatin were then implanted into these defects. Samples from the implant sites were removed after 1, 3, and 6 months postimplantation. Bone regeneration and tissue response were followed by X-ray microcomputed tomography and histological analysis. These in vivo results exhibited osseous tissue integration within the implant and mineralized bone restoration of the calvarium. Both microCT and histological data clearly demonstrated that the more successful results were observed with the "simvastatin-containing PCL scaffolds," in which simvastatin was incorporated into the PCL scaffolds during electrospinning. For these samples, bone mineralization was quite significant when compared with the other groups.

The Effect of Branching (Star Architecture) on Poly(d,l-lactide) (PDLLA) Degradation and Drug Delivery

“…because of anti-inflammatory activity 15,16 , most intriguingly to stimulate bone formation 17 and therefore also as anti-osteoporotic drugs 18,19 , as also demonstrated by previous publications of one of the authors 20 . Although most studies have focused on simvastatin, in this study we have preferred to employ atorvastatin as a model drug, due to its higher (about 2-fold 21 ) activity: simvastatin is per se inactive and requires the hydrolysis of its lactone ring.…”

Bone tissue engineering: A review in bone biomimetics and drug delivery strategies

“…A wide variety of drugs have been encapsulated and released from biodegradable polymer scaffolds including antibiotics, DNA, RNA, cathepsin inhibitors, chitin, chemotherapeutics, bisphosphonates, statins, sodium fluoride, dihydropyridine, and many others. 48,[297][298][299][300] The scope of this section is limited to basic motivation and strategies in encapsulation and local controlled release of antibiotics and chemotherapeutics for the purpose of sepsis and cancer recurrence prevention. Infection is defined as the homeostatic imbalance between the host tissue and the presence of microorganisms at a concentration exceeding 10 5 per gram of tissue.…”

Ring-opening copolymerization of L-lactide and ɛ-caprolactone in supercritical carbon dioxide using triblock oligomers of caprolactone and PEG as stabilizers

“…The polymerization protocol and solubility tests performed are detailed in our previous publication. 38 To determine the effect of the lengths of hydrophilic/hydrophobic segment on copolymerizaton in scCO 2 , the bulk polymerization of the oligomers was conducted by using three different ratios of hydrophilic oligomer (PEG 400) to hydrophobic co-monomer (e-CL) in the initial media: 1/10, 1/25 and 1/50 (mol/mol). For simplification, these SBs are denoted as SB 1 , SB 2 and SB 3, respectively, in the text below.…”

“…Our groups are interested in using these biodegradable polyesters to prepare tissue engineering scaffolds. [38][39][40] Therefore, we have sought SBs that are degradable and safe for medical use to polymerize LLA and e-CL in scCO 2 . In this study, we synthesized triblock copolymers of PEG, which is one of the safest water-soluble polymers used in various medical applications, and e-CL, which is one of the co-monomers used in the final polymer product.…”