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Injection-type platelet lysate-loaded temperature-sensitive hydrogel-high-dispersion nanoparticle system and application thereof

A platelet lysate, temperature-sensitive hydrogel technology, applied in prosthesis, medical science, tissue regeneration, etc., can solve the problems of aggravating patient pain, rapid in-situ degradation, and poor tissue in situ.

Pending Publication Date: 2020-12-22
SHANGHAI SIXTH PEOPLES HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the side effects of long-term oral drug treatment and surgery often aggravate the suffering of patients, so new OA treatment methods need to be developed urgently
In recent years, the intra-articular injection of platelet-rich plasma (PRP) and its derivative platelet lysate (PL) for the treatment of OA has been supported by a large number of studies, which is considered to delay the progression of OA, but it still has local burst release, the original reason Rapid site degradation, poor tissue in-situ and other deficiencies

Method used

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  • Injection-type platelet lysate-loaded temperature-sensitive hydrogel-high-dispersion nanoparticle system and application thereof
  • Injection-type platelet lysate-loaded temperature-sensitive hydrogel-high-dispersion nanoparticle system and application thereof
  • Injection-type platelet lysate-loaded temperature-sensitive hydrogel-high-dispersion nanoparticle system and application thereof

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Experimental program
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preparation example Construction

[0042] Also provide a kind of preparation method of system as described above, the step comprises:

[0043] S1. Preparation of heparin / ε-polylysine nanoparticles loaded with platelet lysate;

[0044] S2. Preparation of thermosensitive hydrogel-platelet lysate-highly dispersed nanoparticle composite system.

[0045] Preferably, the preparation step S1 includes:

[0046] Platelet lysate-loaded heparin / ε-polylysine nanoparticles were prepared by electrostatic self-assembly of heparin and ε-polylysine and the high affinity between heparin and platelet lysate.

[0047] Preferably, the preparation step S2 includes:

[0048] Using Sn(Oct) 2 As a catalyst, initiate ring-opening copolymerization of polyethylene glycol and D,L-lactide to synthesize poly(D,L-lactide)-poly(ethylene glycol)-poly(D,L-lactide) ternary Segment polymer copolymer;

[0049] Hydrocoagulation of heparin / ε-polylysine nanoparticles loaded with platelet lysate embedded in poly(D,L-lactide)-poly(ethylene glycol)-...

Embodiment 1

[0055] Preparation and characterization of heparin (Hep) / ε-polylysine (EPL) nanoparticles (NPs) loaded with platelet lysate:

[0056] As we all know, PL contains complex protein components, of which negatively charged albumin accounts for the majority, and the growth factors that play the main biological activity in PL, including PDGF-BB, TGF-β1, and bFGF, are all negatively charged, and their isoelectric point , are 9.8, 8.9 and 9.6 respectively. Such different charging properties and uneven composition may lead to their aggregation and even precipitation. Dynamic light scattering (DLS) results ( figure 1 and figure 2 ) shows that the particle size distribution of PL is relatively dispersed and irregular (10nm to several microns, average 2089.96±391.23nm). To improve the dispersibility of PL and delay the release of growth factors in PL in a mild loading manner, we prepared PL-loaded NPs solution by taking advantage of the high affinity between Hep and GFs and the electro...

Embodiment 2

[0058] Preparation and characterization of thermosensitive hydrogel-platelet lysate-highly dispersed nanoparticles composite system:

[0059] Use Sn(Oct) 2 As a catalyst, PEG-initiated D,L-lactide was subjected to ring-opening copolymerization to synthesize PLEL triblock copolymers. NMR spectroscopy ( 1 H-NMR)( Figure 5 ) shows that the peaks at 5.10ppm and 1.55ppm represent proton peak (-CH-) and methyl proton peak (-CH 3 ). The peak at 4.30ppm represents the methylene proton peak between D,L-lactide and PEG (-O-CH 2 -CH 2 -), the peak at 3.65ppm corresponds to the methylene proton of PEG (-CH 2 -). Furthermore, Fourier transform infrared spectroscopy (FTIR) plots show ( Figure 6 ), at 1757cm -1 A strong C=O peak appeared at 1097cm -1 The absorption peak at is the representative C-O-C extended PEG –OCH 2 CH 2 The vibration of the repeating unit, at 3664cm -1 The absorption peak at is the terminal hydroxyl group (-OH) of the PLEL copolymer. Simultaneously, DLS ...

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Abstract

The invention relates to an injection-type platelet lysate-loaded temperature-sensitive hydrogel-high-dispersion nanoparticle system. The system comprises temperature-sensitive hydrogel, and a platelet lysate-loaded heparin / epsilon-polylysine nanoparticle embedded into the temperature-sensitive hydrogel. A double slow-release microsphere hydrogel system is designed for the first time to load platelet lysate, and the system is applied to cartilage tissue engineering. The effects of single injection, long-acting slow release and continuous curative effects are achieved. A material is designed according to the characteristics of the platelet lysate itself for the first time, the situation that the platelet lysate with heterogeneous particle distribution can affect the physical characteristicsof the hydrogel is found for the first time, and the situation can be well improved through microsphere construction, so that the constructed material is more reasonable.

Description

technical field [0001] The invention relates to the field of osteoarthritis treatment, in particular to an injection-type temperature-sensitive hydrogel-highly dispersed nanoparticle system loaded with platelet lysate and its application. Background technique [0002] Osteoarthritis (OA) is a degenerative joint disease characterized pathologically by articular cartilage hypertrophy and calcification, subchondral bone remodeling, and synovial inflammation. More than 10% of people over the age of 60 worldwide suffer from OA. Although multiple risk factors, including age, gender, genetic factors, trauma, and obesity, have been reported to be associated with OA, its exact etiology and effective treatment options are still a major clinical problem. The current FDA-approved OA drugs, including non-steroidal anti-inflammatory drugs widely used in early-stage patients, sodium hyaluronate injected into the joint cavity, etc., can only help relieve symptoms, but cannot prevent the de...

Claims

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Application Information

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IPC IPC(8): A61L27/52A61L27/50A61L27/54C08J3/075C08L67/04
CPCA61L27/52A61L27/50A61L27/54C08J3/075A61L2400/06A61L2430/06A61L2400/12A61L2300/602A61L2300/412C08J2367/04
Inventor 唐千朱振中位晓娟张长青
Owner SHANGHAI SIXTH PEOPLES HOSPITAL
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