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Functional reconstruction of injured corpus cavernosa using 3D-printed hydrogel scaffolds seeded with HIF-1?-expressing stem cells.

ABSTRACT: Injury of corpus cavernosa results in erectile dysfunction, but its treatment has been very difficult. Here we construct heparin-coated 3D-printed hydrogel scaffolds seeded with hypoxia inducible factor-1? (HIF-1?)-mutated muscle-derived stem cells (MDSCs) to develop bioengineered vascularized corpora. HIF-1?-mutated MDSCs significantly secrete various angiogenic factors in MDSCs regardless of hypoxia or normoxia. The biodegradable scaffolds, along with MDSCs, are implanted into corpus cavernosa defects in a rabbit model to show good histocompatibility with no immunological rejection, support vascularized tissue ingrowth, and promote neovascularisation to repair the defects. Evaluation of morphology, intracavernosal pressure, elasticity and shrinkage of repaired cavernous tissue prove that the bioengineered corpora scaffolds repair the defects and recover penile erectile and ejaculation function successfully. The function recovery restores the reproductive capability of the injured male rabbits. Our work demonstrates that the 3D-printed hydrogels with angiogenic cells hold great promise for penile reconstruction to restore reproductive capability of males.

SUBMITTER: An G

PROVIDER: S-EPMC7264263 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Functional reconstruction of injured corpus cavernosa using 3D-printed hydrogel scaffolds seeded with HIF-1α-expressing stem cells.

An Geng G Guo Feixiang F Liu Xuemin X Wang Zhifang Z Zhu Ye Y Fan Yong Y Xuan Chengkai C Li Yan Y Wu Hongkai H Shi Xuetao X Mao Chuanbin C

Nature communications 20200601 1

Injury of corpus cavernosa results in erectile dysfunction, but its treatment has been very difficult. Here we construct heparin-coated 3D-printed hydrogel scaffolds seeded with hypoxia inducible factor-1α (HIF-1α)-mutated muscle-derived stem cells (MDSCs) to develop bioengineered vascularized corpora. HIF-1α-mutated MDSCs significantly secrete various angiogenic factors in MDSCs regardless of hypoxia or normoxia. The biodegradable scaffolds, along with MDSCs, are implanted into corpus cavernosa ...[more]

PMID: 32483116

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Project description:INTRODUCTION:Prosthesis-assisted penile reconstruction has been performed extensively to restore a cosmetically acceptable phallus. However, a large number of patients will undergo revision surgery for various prosthesis-related complications. AIM:To develop a 1-stage prosthesis-free dynamic cavernosa reconstruction method using bilateral innervated gracilis muscles and to investigate the feasibility and reliability of the surgical design. METHODS:10 fresh cadavers were dissected to assess the availability of bilateral gracilis muscles for functional cavernosa rebuilding. 11 mongrel female dogs were involved in the penile reconstruction surgery. The neophallus consisted of bilateral gracilis muscles as the neo-cavernosa, a right gracilis skin flap as the neourethra, and a lower abdominal flap with an anterior rectus sheath as the skin envelope and neo-tunica albuginea. The function and structure of the neo-phalli were assessed 7 months postoperatively. MAIN OUTCOME MEASURES:The neurovascular pedicle length of the gracilis muscles and the volume of the gracilis venter musculi were measured in the cadaveric investigation. The average dimensions of the canine neo-phalli at rest and during electrostimulated erection were obtained and the muscular fatigue-resistant curve was drawn. Histologic evaluations also were performed. RESULTS:The neurovascular pedicle length and volume of the gracilis muscles were sufficient to yield a nearly normal appearance of the neo-cavernosa in the cadaveric and animal studies. The muscular fatigue-resistant curve demonstrated adequate length, stiffness, and duration of erection of the neo-phalli to accomplish normal coitus. Histologic evaluations showed an intact neourethra and nearly normal muscle structure in the inner layer of the canine neo-cavernosa, except for significantly increased amount of collagen fibers and type I/III collagen ratio in the outer layer of the neo-cavernosa. The percentage of type II (fatigue-prone) muscle fibers did not change significantly. CONCLUSION:Our preclinical investigation proves that corpora cavernosa reconstruction using bilateral innervated gracilis muscles is technically feasible and functionally efficacious. Yin Z, Liu L, Xue B, et al. Dynamic Penile Corpora Cavernosa Reconstruction Using Bilateral Innervated Gracilis Muscles: A Preclinical Investigation. Sex Med 2018;6:162-170.

Project description:The aim of this study was to predefine the pore structure of ?-tricalcium phosphate (?-TCP) scaffolds with different macro pore sizes (500, 750, and 1000 µm), to characterize ?-TCP scaffolds, and to investigate the growth behavior of cells within these scaffolds. The lead structures for directional bone growth (sacrificial structures) were produced from polylactide (PLA) using the fused deposition modeling techniques. The molds were then filled with ?-TCP slurry and sintered at 1250 °C, whereby the lead structures (voids) were burnt out. The scaffolds were mechanically characterized (native and after incubation in simulated body fluid (SBF) for 28 d). In addition, biocompatibility was investigated by live/dead, cell proliferation and lactate dehydrogenase assays. The scaffolds with a strand spacing of 500 µm showed the highest compressive strength, both untreated (3.4 ± 0.2 MPa) and treated with simulated body fluid (2.8 ± 0.2 MPa). The simulated body fluid reduced the stability of the samples to 82% (500), 62% (750) and 56% (1000). The strand spacing and the powder properties of the samples were decisive factors for stability. The fact that ?-TCP is a biocompatible material is confirmed by the experiments. No lactate dehydrogenase activity of the cells was measured, which means that no cytotoxicity of the material could be detected. In addition, the proliferation rate of all three sizes increased steadily over the test days until saturation. The cells were largely adhered to or within the scaffolds and did not migrate through the scaffolds to the bottom of the cell culture plate. The cells showed increased growth, not only on the outer surface (e.g., 500: 36 ± 33 vital cells/mm² after three days, 180 ± 33 cells/mm² after seven days, and 308 ± 69 cells/mm² after 10 days), but also on the inner surface of the samples (e.g., 750: 49 ± 17 vital cells/mm² after three days, 200 ± 84 cells/mm² after seven days, and 218 ± 99 living cells/mm² after 10 days). This means that the inverse 3D printing method is very suitable for the presetting of the pore structure and for the ingrowth of the cells. The experiments on which this work is based have shown that the fused deposition modeling process with subsequent slip casting and sintering is well suited for the production of scaffolds for bone replacement.

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Functional reconstruction of injured corpus cavernosa using 3D-printed hydrogel scaffolds seeded with HIF-1?-expressing stem cells.

Publications

Functional reconstruction of injured corpus cavernosa using 3D-printed hydrogel scaffolds seeded with HIF-1α-expressing stem cells.

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