Attachment of nanoparticulate drug-release systems on poly(ε-caprolactone) nanofibers via a graftpolymer as interlayer

Cassan, Dominik de; Sydow, Steffen; Schmidt, Nadeschda; Behrens, Peter; Roger, Yvonne; Hoffmann, Andrea; Hoheisel, Anna Lena; Glasmacher, Birgit; Hänsch, Robert; Menzel, Henning

doi:10.1016/j.colsurfb.2017.12.050

Cited by 35 publications

(68 citation statements)

References 63 publications

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“…In further approaches, we want to optimize the PCL fiber patches by increasing the pores to sizes greater than 300 μm for optimal vascularization (Kuboki, Jin, & Takita, ). Moreover, the cationic amino groups provided by chitosan open a great variety to adsorb oppositely charged nanoparticulate drug‐carrier systems (Sydow et al, ) or to enable further chemical modifications of the implant surface (de Cassan et al, ; Hofer & Tuan, ; Lopiz et al, ). Especially, growth or differentiation factors that support tendon repair processes both on the tendon‐muscular as well as on the tendon‐bone side are of great interest in this context.…”

Section: Discussionmentioning

confidence: 99%

“…These scaffolds were then modified using CS‐g‐PCL (described in de Cassan et al, ). CS‐g‐PCL is bound to PCL fiber surface by crystallization according to established methods (Wang et al, ).…”

Section: Methodsmentioning

confidence: 99%

“…Whereas the surface angle of unmodified PCL fibers was 124°, it was decreased to 34° in CS‐g‐PLC, and possible drug delivery systems were already addressed. (de Cassan et al, ). The improved vascularization and cellular attachment of this surface‐modified PCL compared with the unmodified material could be shown in in vitro cell culture studies (de Cassan et al, ) and in a special femur chamber model, where progressing graft vascularization can be monitored microscopically with fluorescence staining in vivo for up to 21 days followed by a histological evaluation at the end of the study period for further cellular characterization (Gniesmer et al, ).…”

Section: Introductionmentioning

confidence: 99%

“…(de Cassan et al, ). The improved vascularization and cellular attachment of this surface‐modified PCL compared with the unmodified material could be shown in in vitro cell culture studies (de Cassan et al, ) and in a special femur chamber model, where progressing graft vascularization can be monitored microscopically with fluorescence staining in vivo for up to 21 days followed by a histological evaluation at the end of the study period for further cellular characterization (Gniesmer et al, ). De Cassan et al reported a good adhesion and morphology of human mesenchymal stromal cells in contact to CS‐g‐PCL, and Gniesmer et al showed a significantly increased vascularization combined with a thinner ensheathing fibrous capsule in CS‐g‐PCL‐coated fiber mats compared with uncoated PCL fiber mats or to a commercially available polyurethane based scaffold (Biomerix 3D Scaffold).…”

Section: Introductionmentioning

confidence: 99%

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Possibilities and limitations of electrospun chitosan‐coated polycaprolactone grafts for rotator cuff tear repair

Willbold

Wellmann

Welke

et al. 2019

J Tissue Eng Regen Med

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Acute and chronic rotator cuff tears remain challenging for therapy. A wide range of therapeutic approaches were developed but re-tears and postoperative complications occur regularly. Especially in elderly people, the natural regeneration processes are decelerated, and graft materials are often necessary to stabilize the tendon-to-bone attachment and to improve the healing process. We here investigated in a small animal model a newly developed electrospun polycaprolactone fiber implant coated with a chitosan-polycaprolactone graft copolymer and compared these implants biomechanically and histologically with either a commercially available porous polyurethane implant (Biomerix 3D Scaffold) or suture-fixed tendons. Fifty-one rats were divided into three groups of 17 animals each. In the first surgery, the left infraspinatus tendons of all rats were detached, and the animals recovered for 4 weeks. In the second surgery, the tendons were fixed with suture material only (suture-fixed group; n = 17), whereas in the two experimental groups, the tendons were fixed with suture material and the polyurethane implant (Biomerix scaffold group; n = 17) or the modified electrospun polycaprolactone fiber implant (CS-g-PCL scaffold group; n=17), respectively. The unaffected right infraspinatus tendons were used as native controls. After a recovery of 8 weeks, all animals were clinically inconspicuous. In 12 animals of each group, repaired entheses were biomechanically tested for force at failure, stiffness, and modulus of elasticity, and in five animals, repaired entheses were analyzed histologically. Biomechanically, all parameters did not differ statistically significant between both implant groups, and the entheses failed typically at the surgical site.However, with respect to the force at failure, the median values of the two implant groups were smaller than the median value of the suture-fixed group. Histologically, the modified polycaprolactone fiber implant showed no acute inflammation processes, a good infiltration with cells, ingrowth of blood vessels and tendinous tissue, and a normal fibrous ensheathment. Further improvement of the implant material could be achieved by additional implementation of drug delivery systems. Therewith, the used CS-g-PCL fiber mat is a promising basic material to reach the goal of a clinically usable graft for rotator cuff tear repair.Elmar Willbold and Mathias Wellmann contributed equally to this work

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Possibilities and limitations of electrospun chitosan‐coated polycaprolactone grafts for rotator cuff tear repair

Willbold

Wellmann

Welke

et al. 2019

J Tissue Eng Regen Med

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“…Therefore, PCL is unattractive for biomedical applications (Nair & Laurencin, ). Furthermore, because PCL is an aliphatic polyester, it lacks access to easy modifications, and chemically more reactive moieties have to be introduced by various approaches such as plasma or wet chemical treatment, blending, and attachment of graft copolymers (Fu, Sammons, Bertóti, Jenkins, & Dong, ; Tallawi et al, ; de Cassan et al, ). These modifications can help overcome these weaknesses of PCL, while maintaining good properties, and create implants applicable in a variety of orthopaedic areas, for example, the use in therapy of chronic rotator cuff tears.…”

Section: Introductionmentioning

confidence: 99%

In vivo analysis of vascularization and biocompatibility of electrospun polycaprolactone fibre mats in the rat femur chamber

Gniesmer

Brehm²,

Hoffmann

et al. 2019

J Tissue Eng Regen Med

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In orthopaedic medicine, connective tissues are often affected by traumatic or degenerative injuries, and surgical intervention is required. Rotator cuff tears are a common cause of shoulder pain and disability among adults. The development of graft materials for bridging the gap between tendon and bone after chronic rotator cuff tears is essentially required. The limiting factor for the clinical success of a tissue engineering construct is a fast and complete vascularization of the construct. Otherwise, immigrating cells are not able to survive for a longer period of time, resulting in the failure of the graft material. The femur chamber allows the observation of microhaemodynamic parameters inside implants located in close vicinity to the femur in repeated measurements in vivo. We compared a porous polymer patch (a commercially available porous polyurethane‐based scaffold from Biomerix™) with electrospun polycaprolactone (PCL) fibre mats and chitosan (CS)‐graft‐PCL modified electrospun PCL (CS‐g‐PCL) fibre mats in vivo. By means of intravital fluorescence microscopy, microhaemodynamic parameters were analysed repetitively over 20 days at intervals of 3 to 4 days. CS‐g‐PCL modified fibre mats showed a significantly increased vascularization at Day 10 compared with Day 6 and at Day 14 compared with the porous polymer patch and the unmodified PCL fibre mats at the same day. These results could be verified by histology. In conclusion, a clear improvement in terms of vascularization and biocompatibility is achieved by graft‐copolymer modification compared with the unmodified material.

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Blending chitosan‐g‐poly(caprolactone) with poly(caprolactone) by electrospinning to produce functional fiber mats for tissue engineering applications

Cassan

Becker

Glasmacher

et al. 2019

J of Applied Polymer Sci

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Use of electrospun fiber mats for tissue engineering applications has become increasingly prominent. One of the most important polymers in research, poly(ε-caprolactone) (PCL), however, lacks biological performance, easy access to modifications and cellular recognition sites. To improve these properties and to enable further modifications, PCL was blended with chitosan grafted with PCL (CS-g-PCL) and subsequently processed via electrospinning. In this way, chitosan was enriched at the fiber's surface presenting cationic amino groups. The fiber mats were analyzed by various techniques such as scanning electron microscopy (SEM), confocal laser scanning microscopy (CLSM), and X-ray photoelectron spectroscopy (XPS). Furthermore, analyzing thermal properties and crystallinity, showed that an increased content of CS-g-PCL in blend composition leads to a higher overall crystallinity in produced fiber mats. Blending CS-g-PCL into PCL significantly increased initial cellular attachment and proliferation as well as cell vitality, while maintaining adequate mechanical properties, fiber diameter, and interstitial volume. As proof of principle for easy access to further modification, fluorescently labeled alginate (Alg-FA) was attached to the fiber's surface and verified by CLSM. Hence, blending CS-g-PCL with PCL can overcome an inherent weakness of PCL and create bioactive implants for tissue engineering applications.

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Attachment of nanoparticulate drug-release systems on poly(ε-caprolactone) nanofibers via a graftpolymer as interlayer

Cited by 35 publications

References 63 publications

Possibilities and limitations of electrospun chitosan‐coated polycaprolactone grafts for rotator cuff tear repair

Possibilities and limitations of electrospun chitosan‐coated polycaprolactone grafts for rotator cuff tear repair

In vivo analysis of vascularization and biocompatibility of electrospun polycaprolactone fibre mats in the rat femur chamber

Blending chitosan‐g‐poly(caprolactone) with poly(caprolactone) by electrospinning to produce functional fiber mats for tissue engineering applications

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