Bone regeneration in osteoporosis by delivery BMP-2 and PRGF from tetronic–alginate composite thermogel

González, Enrique; García-García, Patricia; Reyes, Ricardo; Pérez-Herrero, Edgar; Delgado, Araceli; Évora, Carmen

doi:10.1016/j.ijpharm.2018.03.034

Cited by 52 publications

(33 citation statements)

References 46 publications

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“…In addition, microsphere-incorporating scaffolds provide appropriated mechanical properties for in vitro culture. In our system, we obtained microspheres diameter mean volume of 59.31 µm (10% < 26.75 µm and 90% < 84.23 µm), with capacity for high drug loading yield and a tunable sustained release 22 , which would be ready for fast testing in animal models after the in vitro assay 23,24 .…”

Section: Resultsmentioning

confidence: 99%

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Organotypic culture as a research and preclinical model to study uterine leiomyomas

Salas

López

Reyes

et al. 2020

Sci Rep

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Organotypic cultures of tissue slices have been successfully established in lung, prostate, colon, gastric and breast cancer among other malignancies, but until now an ex vivo model based on tissue slices has not been established for uterine leiomyoma. In the present study, we describe a method for culturing tumour slides onto an alginate scaffold. Morphological integrity of tissue slices was maintained for up to 7 days of culture, with cells expressing desmin, estrogen and progesterone receptors. Driver mutations were present in the ex vivo slices at all-time points analyzed. cultivated tumour slices responded to ovarian hormones stimulation upregulating the expression of genes involved in leiomyoma pathogenesis. This tissue model preserves extracellular matrix, cellular diversity and genetic background simulating more in-vivo-like situations. As a novelty, this platform allows encapsulation of microspheres containing drugs that can be tested on the ex vivo tumour slices. After optimizing drug release rates, microspheres would then be directly tested in animal models through local injection. Uterine leiomyoma (UL), also called fibroid or myoma, is the most commonly diagnosed tumour of the female genital tract with an incidence of 40% at the age of 35 and nearly 70-80% around the age of 50 1,2. Severe symptoms develop in 15-30% of patients being irregular, prolonged or heavy vaginal bleeding the most common manifestations frequently associated with moderate to severe anemia 1. In addition, UL may interfere with embryo implantation, complications during pregnancy and childbirth, decreasing reproductive success 3. Fibroids are the leading cause of hysterectomy with an estimated US healthcare cost of ~$21 billion annually 4. Although the etiology remains elusive, some progress has been made about the molecular mechanisms involved in tumour initiation and growth including (1) steroid hormone-dependency 2 , (2) excessive accumulation of extracellular matrix (ECM), a reservoir for growth factors, cytokines, chemokines, angiogenic and inflammatory response mediators and proteases that contribute to cell growth, differentiation and ECM turnover 5,6 and (3) alterations in driver genes such as HMGA2 (high mobility group AT-hook 2) and MED12 (mediator complex subunit 12) occurring in most of the tumours 7,8. Different cell populations are found in leiomyomas, including smooth muscle (SMC), fibroblast and stem cells 9-12 , all of them embedded in the abundant ECM. Communication between these cells seems to be critical for tumour proliferation and survival 9-11. Thus, it has been proposed that leiomyoma stem-progenitor cells devoid of sex hormonal receptors, respond to paracrine signals sent by surrounding tumour cells upon ovarian steroid stimulation, inducing self-renewal and tumour maintenance and growth 13. Furthermore, UL derived fibroblast stimulate the proliferation of leiomyoma cells and collagen type I production 6,11,14. Most studies published to date have used traditional 2D culture models of primary or immortalize...

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Section: Resultsmentioning

confidence: 99%

“…Microspheres size distribution was determined by laser diffractometry (Mastersizer 2000, Malvern Instruments, Malvern, UK). Porosity of the scaffolds was calculated as previously 23 and scaffold thickness was measured from photographs obtained by stereo-microscopy (Leica M205C, Leica LAS, v3 software, Germany). organotypic tissue culture.…”

Section: Discussionmentioning

confidence: 99%

Organotypic culture as a research and preclinical model to study uterine leiomyomas

Salas

López

Reyes

et al. 2020

Sci Rep

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“…Local application of the GF rich gel was able to induce bone regeneration in osteoporotic female rats. [ 108 ] The hydrogel system is composed of a poloxamine (T‐1307) reinforced with calcium chloride crosslinked alginate. PRGF and BMP‐2 were encapsulated within PLGA microspheres.…”

Section: Stimuli‐responsive Growth Factor Delivery Systems In Tissue mentioning

confidence: 99%

Stimuli‐Responsive Delivery of Growth Factors for Tissue Engineering

Jiang

Zhou

et al. 2020

Adv Healthcare Materials

105

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Growth factors (GFs) play a crucial role in directing stem cell behavior and transmitting information between different cell populations for tissue regeneration. However, their utility as therapeutics is limited by their short half‐life within the physiological microenvironment and significant side effects caused by off‐target effects or improper dosage. “Smart” materials that can not only sustain therapeutic delivery over a treatment period but also facilitate on‐demand release upon activation are attracting significant interest in the field of GF delivery for tissue engineering. Three properties are essential in engineering these “smart” materials: 1) the cargo vehicle protects the encapsulated therapeutic; 2) release is targeted to the site of injury; 3) cargo release can be modulated by disease‐specific stimuli. The aim of this review is to summarize the current research on stimuli‐responsive materials as intelligent vehicles for controlled GF delivery; Five main subfields of tissue engineering are discussed: skin, bone and cartilage, muscle, blood vessel, and nerve. Challenges in achieving such “smart” materials and perspectives on future applications of stimuli‐responsive GF delivery for tissue regeneration are also discussed.

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“…The analysis showed that the bone mineralization was higher for the rats without osteoporosis than for the ill rats. The study also revealed that the BMP2 improved the response to 17βestradiol (Segredo-Morales et al, 2018).…”

Section: New Approaches For Alginate-based Biomaterialsmentioning

confidence: 79%

A review of chitosan-, alginate-, and gelatin-based biocomposites for bone tissue engineering

2018

Biomater Tissue Eng Bull

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Bone diseases and injuries have a major impact on the quality of life. Classical treatments for bone repair/regeneration/replacement have various disadvantages. Bone tissue engineering (BTE) received a great attention in the last years. Natural polymers are intensively studied in this field due to their properties (biocompatibility, biodegradability, abundance in nature, high processability). Unfortunately, their mechanical properties are poor, which is why synthetic polymers or ceramics are added in order to provide the optimal compressive, elastic or fatigue strength. Moreover, growth factors, vitamins, or antimicrobial substances are also added to enhance the cell behavior (attachment, proliferation, and differentiation). In this review, new scientific results regarding potential applications of chitosan-, alginate-, and gelatin based biocomposites in BTE will be provided, along with their in vitro and/or in vivo tests.

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Bone regeneration in osteoporosis by delivery BMP-2 and PRGF from tetronic–alginate composite thermogel

Cited by 52 publications

References 46 publications

Organotypic culture as a research and preclinical model to study uterine leiomyomas

Organotypic culture as a research and preclinical model to study uterine leiomyomas

Stimuli‐Responsive Delivery of Growth Factors for Tissue Engineering

A review of chitosan-, alginate-, and gelatin-based biocomposites for bone tissue engineering

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