Soft and hard tissue response to photocrosslinked poly(propylene fumarate) scaffolds in a rabbit model

Abstract

The treatment of large cranial defects may be greatly improved by the development of precisely formed bone tissue engineering scaffolds. Such scaffolds could be constructed by using UV laser stereolithography to photocrosslink a linear, biodegradable polymer into a three-dimensional implant. We have previously presented a method to photocrosslink the biodegradable polyester, poly(propylene fumarate) (PPF). To ensure the safety and effectiveness of this technique, the soft and hard tissue response to photocrosslinked PPF scaffolds of different pore morphologies was investigated. Four classes of photocrosslinked PPF scaffolds, constructed with differing porosities (57-75%) and pore sizes (300-500 or 600-800 microm), were implanted both subcutaneously and in 6.3-mm-diameter cranial defects in a rabbit model. The rabbits were sacrificed at 2 and 8 weeks, and the implants were analyzed by light microscopy, histological scoring analysis, and histomorphometric analysis. Results showed the PPF scaffolds elicit a mild tissue response in both soft and hard tissues. Inflammatory cells, vascularization, and connective tissue were observed at 2 weeks; a decrease in inflammatory cell density and a more organized connective tissue were observed at 8 weeks. Scaffold porosity and scaffold pore size were not found to significantly affect the observed tissue response. Evidence of scaffold surface degradation was noted both by histology and histomorphometric analysis. Bone ingrowth in PPF scaffolds implanted into cranial defects was <3% of the defect area. The results indicate that photocrosslinked PPF scaffolds are biocompatible in both soft and hard tissues and thus may be an attractive platform for bone tissue engineering.

Injectable Biodegradable Polyurethane Scaffolds with Release of Platelet-derived Growth Factor for Tissue Repair and Regeneration

“…Recently developed porous composite scaffolds have been formed in situ by gas foaming, with up to 61% porosity, 50-500 m pores, and a compressive modulus of . PPF biomaterials have been shown to support osteoblast attachment and proliferation in vitro, and ingrowth of new bone tissue in vivo (16)(17)(18)(19). Growth factors have been incorporated via PLGA micro-spheres into poly(propylene fumarate) materials for controlled release (20).…”

Reinforced Pericardium as a Hybrid Material for Cardiovascular Applications

“…For this purpose, the synthetic polymer poly(propylene fumarate) (PPF) was selected for its demonstrated biocompatibility, biodegradability, and strength in other biomedical applications. 18,19 PPF is an unsaturated linear polyester that is crosslinkable through UV radiation with itself or with other compatible crosslinkers through the double bonds in fumarate. PPF is biodegradable by hydrolysis of ester bonds and forms the naturally occurring byproducts fumaric acid and propylene glycol upon degradation.…”

Targeted mechanical properties for optimal fluid motion inside artificial bone substitutes

“…For the particular case of high tibial osteotomy, a minimum elastic modulus of 500 MPa was needed for structural stability of the tibial plateau during gait, a minimum Poisson's ratio of 0.1 was assumed to avoid specific processing procedures, 38,39 and a minimum porosity of 50% was required to ensure good osteointegration. 4,14,40 As a result, high tibial osteotomy using a bone substitute material with these properties is likely to maximize fluid flow and favor rapid osteointegration. A bone substitute covering one-quarter of the osteotomy cross section exchanged 2.2% of its fluid content during each gait cycle for an optimized material compared to 0.6 and 0.4% for a substitute made of cancellous bone or coralline hydroxylapatite.…”

“…38,39 Finally, the range of porosity values was limited between 50 and 90% as good in vivo osteointegration was reported for various materials with these porosities. 4,14,40,41 According to the optimization scheme, bone substitutes with elastic modulus of 500 MPa, Poisson's ratio of 0.1, and porosity of 50% are likely to maximize the proportion of fluid exchange. A 1 cm edge cubic bone substitute exchanged 10% of its fluid content with its environment during one gait cycle (Fig.…”

“…[1][2][3][4][5] Thus, novel artificial bone substitutes can be customized as to their physical properties. The question becomes which material favored best osteointegration in order to shorten the postoperative recovery phase.…”