Injectable hydrogel microsphere for treating orthopedic diseases as well as preparation method and application thereof

A technology of hydrogel microspheres and orthopedic diseases, applied in the field of biomedical materials, can solve the problems of difficult and minimally invasive injection of GelMA hydrogel, and achieve the effects of promoting bone healing, achieving controlled release, good treatment and repair

Active Publication Date: 2021-04-09
杭州贤石生物科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, bulk GelMA hydrogels are difficult to achieve minimally invasive injection applications without special technical improvements such as in situ cross-linking or shear-thinning cross-linking.

Method used

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  • Injectable hydrogel microsphere for treating orthopedic diseases as well as preparation method and application thereof
  • Injectable hydrogel microsphere for treating orthopedic diseases as well as preparation method and application thereof
  • Injectable hydrogel microsphere for treating orthopedic diseases as well as preparation method and application thereof

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0050] A method for preparing hydrogel microspheres, which uses one-step microfluidic technology and photochemical cross-linking reaction to incorporate highly dispersed fullerenol nanocrystals with enhanced biological reactivity into hydrogel microspheres to construct rich Letol functional microfluidic spheres (FMS) as stem cell carriers to in situ regulate redox homeostasis in refractory bone healing (specific steps as figure 1 ).

[0051] Such as figure 1 As shown, in a) from left to right are the three-dimensional structure of FMS, the molecular structure of fullerenol and the structural schematic diagram of gelatin methacryloyl (GelMA). To reveal the three-dimensional structure, the hydrogel matrix network of FMS is rendered in different colors in the figure. Through the physical entanglement of the hydrogel matrix network and the non-covalent interaction between GelMA and fullerenol, the fullererol was immobilized within the hydrogel microspheres.

[0052] b) is a sch...

Embodiment 2

[0057] Characterize the FMS, the results are as follows figure 2 .

[0058] Such as figure 2 As shown, a) is the SEM image of FMS; b) is the LSCM image of FMS embedded with alizarin red (i) and calcein (ii). Alizarin red and calcein were incorporated into the GelMA pre-solution and then photochemically cross-linked into dye-labeled FMS. c) Light microscope image of FMS. d) is the particle size distribution of FMS. e) TEM image of fullerenol nanocrystals in FMS. The FMS was degraded by type II collagenase solution, and the free fullerenol nanocrystals in the aqueous solution were detected by TEM. f) Gross photographs of FMS containing different concentrations of fullerenol (0, 1, 10, 100 and 200 μM).

[0059] FMS is prepared by a modified microfluidic device [1]. The device includes a water phase and an oil phase, wherein the water phase is composed of fullererol and 5wt% GelMA pre-solution containing 0.5wt% photoinitiator, while the oil phase is composed of paraffin o...

Embodiment 3

[0066] Incubate FMS with collagenase for degradation analysis, the results are as follows image 3 .

[0067] image 3 In, a) Microscope images showing the morphological changes of FMS over 5 weeks. In the early stage, the fine particles around the FMS increased, and in the later stage, cracks or fractures appeared near the FMS. b) is the remaining weight of FMS (n=3). c) is the TEM image of fullerenol nanocrystals in the degradation solution after 5 weeks.

[0068] To evaluate the ability of FMS as a stem cell carrier to repair bone defects, its degradation properties were investigated. Previous studies used 2U mL -1 Collagenase solution to study the degradation properties of GelMA hydrogels [1]. However, at 2U mL -1 In the collagenase solution, FMS was rapidly degraded within hours, which may be due to the larger specific surface area of ​​FMS compared with bulk hydrogel, which accelerated the enzymatic degradation reaction. In fact, a few hours is too fast to observ...

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Abstract

The invention provides an injectable hydrogel microsphere for treating orthopedic diseases as well as a preparation method and application thereof. A hydrogel microsphere is taken as a matrix, a substance capable of enhancing the biological reaction activity is doped into the hydrogel microsphere, and a functionalized hydrogel microsphere is prepared by adopting a microfluidic technology and a photochemical cross-linking reaction. The orthopedic diseases include refractory bone healing or osteoarthritis. The substance capable of enhancing the biological reaction activity includes any one of fullerol nanocrystals, lipidosome loaded with KGN, and a copolymer obtained from dopamine methacrylamide and sulfobetaine methacrylate. The preparation method provided by the invention is simple, a prepared microgel material can effectively remove ROS, a good microenvironment is created for survival of mesenchymal stem cells, and osteogenic differentiation of the mesenchymal stem cells is promoted; and meanwhile, the drug loading stability can be improved, the controlled release of a drug is realized, and the effect of well treating and repairing the orthopedic diseases can be achieved.

Description

technical field [0001] The invention belongs to the technical field of biomedical materials, and relates to a microgel material, in particular to an injectable hydrogel microsphere for treating orthopedic diseases, a preparation method and application thereof. Background technique [0002] Orthopedic disease is a clinical condition that people often face. For example, restoration of massive bone loss and defects is the challenge of modern orthopedics. In the case of aging and other diseases such as diabetes or osteoporosis, this The difficulty of repairing orthopedic diseases will be intensified, which makes refractory bone repair an extremely difficult medical problem and seriously endangers the health of individuals around the world. In addition, osteoarthritis (OA) is also a common orthopedic disease, which is a debilitating joint disease, its incidence increases with age, mainly manifested by persistent pain and immobility, which Seriously impairs an individual's physic...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K35/28A61K31/196A61K9/52A61K9/06A61K47/69A61K47/42A61K47/32A61P19/08A61P19/02A61P29/00
CPCA61K35/28A61K31/196A61K9/0019A61K9/06A61K9/5057A61K9/5026A61K9/5089A61K47/6949A61P19/08A61P19/02A61P29/00
Inventor 崔文国杨接来林佳炜朱渊齐进王非卢敏梁静徐向阳邓廉夫
Owner 杭州贤石生物科技有限公司
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