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

Gniesmer, Sarah; Brehm, Ralph; Hoffmann, Andrea; Cassan, Dominik de; Menzel, Henning; Hoheisel, Anna-Lena; Glasmacher, Birgit; Willbold, Elmar; Reifenrath, Janin; Wellmann, Mathias; Ludwig, Nils; Tavassol, Frank; Zimmerer, Rüdiger; Gellrich, Nils‐Claudius; Kampmann, Andreas

doi:10.1002/term.2868

Cited by 29 publications

(35 citation statements)

References 51 publications

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“…This characterization technique based on the displacement of a wetting liquid (Porofil1, Quantachrome GmbH & Co. KG) from the pores of the sample by increasing the pressure from an inert gas. The underlying equations for the calculation of the porosity and the pore diameter were described elsewhere [26]. The porosity and the pore diameter of the reticulated polyurethane based scaffold was evaluated in a previous study [26].…”

Section: Evaluation Of Porosity and Pore Diametermentioning

confidence: 99%

“…The underlying equations for the calculation of the porosity and the pore diameter were described elsewhere [26]. The porosity and the pore diameter of the reticulated polyurethane based scaffold was evaluated in a previous study [26].…”

Section: Evaluation Of Porosity and Pore Diametermentioning

confidence: 99%

“…The specific design of the fiber mat in turn stimulates the regeneration of organized tendon structures. In a previous study we analyzed electrospun PCL fiber mats with undirected fiber orientation, that were intended to mimic the specific fiber orientation at the tendon-bone transition in the femur chamber in rats [26]. In this study fiber mats with directed fiber structures were used to simulate the tendonmuscle transition.…”

Section: Introductionmentioning

confidence: 99%

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Vascularization and biocompatibility of poly(ε-caprolactone) fiber mats for rotator cuff tear repair

Gniesmer

Brehm²,

Hoffmann

et al. 2020

PLoS ONE

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Rotator cuff tear is the most frequent tendon injury in the adult population. Despite current improvements in surgical techniques and the development of grafts, failure rates following tendon reconstruction remain high. New therapies, which aim to restore the topology and functionality of the interface between muscle, tendon and bone, are essentially required. One of the key factors for a successful incorporation of tissue engineered constructs is a rapid ingrowth of cells and tissues, which is dependent on a fast vascularization. The dorsal skinfold chamber model in female BALB/cJZtm mice allows the observation of microhemodynamic parameters in repeated measurements in vivo and therefore the description of the vascularization of different implant materials. In order to promote vascularization of implant material, we compared a porous polymer patch (a commercially available porous polyurethane based scaffold from Biomerix™) with electrospun polycaprolactone (PCL) fiber mats and chitosan-graft-PCL coated electrospun PCL (CS-g-PCL) fiber mats in vivo. Using intravital fluorescence microscopy microcirculatory parameters were analyzed repetitively over 14 days. Vascularization was significantly increased in CS-g-PCL fiber mats at day 14 compared to the porous polymer patch and uncoated PCL fiber mats. Furthermore CS-g-PCL fiber mats showed also a reduced activation of immune cells. Clinically, these are important findings as they indicate that the CS-g-PCL improves the formation of vascularized tissue and the ingrowth of cells into electrospun PCL scaffolds. Especially the combination of enhanced vascularization and the reduction in immune cell activation at the later time points of our study points to an improved clinical outcome after rotator cuff tear repair.

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Section: Evaluation Of Porosity and Pore Diametermentioning

confidence: 99%

Section: Evaluation Of Porosity and Pore Diametermentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Vascularization and biocompatibility of poly(ε-caprolactone) fiber mats for rotator cuff tear repair

Gniesmer

Brehm²,

Hoffmann

et al. 2020

PLoS ONE

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“…Here, mats of CS‐g‐PCL‐coated PCL also significantly improved the vascularization when compared with Biomerix 3D Scaffold mats. Using unmodified PCL fiber mats, the vascular structures were only present around the implant (Gniesmer et al, ).…”

Section: Discussionmentioning

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: 95%

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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Understanding the In Vivo Fate of Advanced Materials by Imaging

Garlin

et al. 2020

Adv Funct Materials

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Engineered materials are ubiquitous in biomedical applications ranging from systemic drug delivery systems to orthopedic implants, and their actions unfold across multiple time‐ and length‐scales. The efficacy and safety of biologics, nanomaterials, and macroscopic implants are all dictated by the same general principles of pharmacology as applied to small molecule drugs, comprising how the body affects materials (pharmacokinetics, PK) and conversely how materials affect the body (pharmacodynamics, PD). Imaging technologies play an increasingly insightful role in monitoring both of these processes, often simultaneously: translational macroscopic imaging modalities such as magnetic resonance imaging and positron emission tomography/computed tomography offer whole‐body quantitation of biodistribution and structural or molecular response, while ex vivo approaches and optical imaging via in vivo (intravital) microscopy reveal behaviors at subcellular resolution. In this review, the authors survey developments in imaging the in situ behavior of systemically and locally administered materials, with a particular focus on using microscopy to understand transport, target engagement, and downstream host responses at a single‐cell level. The themes of microenvironmental influence, controlled drug release, on‐target molecular action, and immune response, especially as mediated by macrophages and other myeloid cells, are examined. Finally, the future directions of how new imaging technologies may propel efficient clinical translation of next‐generation therapeutics and medical devices are proposed.

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

Cited by 29 publications

References 51 publications

Vascularization and biocompatibility of poly(ε-caprolactone) fiber mats for rotator cuff tear repair

Vascularization and biocompatibility of poly(ε-caprolactone) fiber mats for rotator cuff tear repair

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

Understanding the In Vivo Fate of Advanced Materials by Imaging

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