JP6901166B2 - 磁気駆動関節軟骨再生システム - Google Patents
磁気駆動関節軟骨再生システム Download PDFInfo
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- JP6901166B2 JP6901166B2 JP2019523699A JP2019523699A JP6901166B2 JP 6901166 B2 JP6901166 B2 JP 6901166B2 JP 2019523699 A JP2019523699 A JP 2019523699A JP 2019523699 A JP2019523699 A JP 2019523699A JP 6901166 B2 JP6901166 B2 JP 6901166B2
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Description
本明細書で使用される用語「骨関節炎」は、退行性関節炎とも言い、局所的な関節に漸進的な関節軟骨の消失及びそれと関連した二次的な変化と症状とを伴う疾患であって、関節を保護している軟骨の漸進的な損傷や退行性変化によって、関節を成す骨と靭帯などに損傷が起こって、炎症と疼痛とが生じる疾患である。
本発明の一態様によれば、磁性体及び軟骨生成細胞が付着された微細構造体を含む軟骨再生用組成物が提供される。
本発明の一実施例によって、PLGAマイクロスキャフォールドボディー(micro−scaffold body)は、少し変形されたプロセスを有した流体装置(fluidic device)を利用した二重エマルジョン(double emulsion)方法によって準備した。
本発明の一実施例によって、前記実施例1から製作されたスキャフォールドボディーに電磁駆動能力を付与するためのアミン機能化Fe3O4 MNPsを製造した。
本発明の一実施例によって、PLGAマイクロスキャフォールドの表面に、前記実施例2から製作されたFe3O4 MNPがコーティングされたPEIを付着するために、アミノ結合形成(amino bond formation)を利用した結合工程(coupling process)を利用した。まず、PLGAスキャフォールドを、33℃で1.5mM NHS(N−hydroxysuccinimide)及びEDC(1−Ethyl−(dimethylaminopropyl)carbodiimide)が添加された5ml MES(0.1M)溶液に浸漬した。マイクロスキャフォールドを含む溶液を、PLGAマイクロスキャフォールドの表面でカルボキシル基(carboxyl groups)を活性化するために、6時間機械的に撹拌した。マイクロスキャフォールド表面の活性化後に、5ml MES(0.1M)から変形されたMNPs(10mg/ml)が分散されたPEIを前記溶液に添加し、33℃で12時間撹拌した。その後、前記溶液を、無反応(unreactive)MNPsを除去するために濾過し、フィルターで固定化されたマイクロスキャフォールドのMNPsを収集し、脱イオン水で3回洗浄した。
10% FBS含むDMEM培地内に、前記実施例3から製造された磁性ナノ粒子(MNP)が付着されたマイクロスキャフォールドを浸漬させた後、顕微鏡下でマウス骨髄由来間葉幹細胞(MSC)1×106cells/scaffoldを前記マイクロスキャフォールド上に注入した後、5% CO2培養器に37℃で培養し、2日ごとに培養液を取り替えて、前記マイクロスキャフォールド内に前記間葉幹細胞を定着させた。この際、対照群として磁性ナノ粒子が付着されていないマイクロスキャフォールドに同じ濃度の間葉幹細胞を注入した。
本発明者らは、前記実施例4から製造された間葉幹細胞が導入されたマイクロスキャフォールド構造体に付着された間葉幹細胞が実際に軟骨細胞に分化されるかについて、軟骨細胞分化能を調査した。
本発明の一実施例によって、MNPsが導入されたマイクロスキャフォールド間葉幹細胞複合体が、本発明の磁気駆動システムを通じて移動調節が可能か否かを確認するために、微細流体チャンバを利用した2D磁気駆動の実験を行った。
本発明の一実施例によって、製作した磁気駆動マイクロスキャフォールドの関節欠損部位への標的能を観察した。まず、3D標的能テストのための膝ファントム(knee phantom)は、膝の3D CADモデルから3Dプリンターを用いて製作した(図10)。その後、標的領域に深さ3mm、直径2mmの穴を大腿骨(femur)の内側に形成した。3D標的能テストのために、前記製造されたモデルを、グリセリン(70wt%)溶液を満たしたアクリルチャンバに位置させた。その後、5個のマイクロスキャフォールドが、ピペッティングによって膝モデルファントムの関節欠損部位の間に注入され、標的領域への移動を観察した。
<付記>
<項1>
磁性体及び軟骨生成細胞が付着された微細構造体を含む軟骨再生用組成物。
<項2>
前記軟骨生成細胞は、軟骨細胞または幹細胞である<項1>に記載の組成物。
<項3>
前記幹細胞は、骨髄由来幹細胞または脂肪由来幹細胞である<項2>に記載の組成物。
<項4>
前記磁性体は、磁性ナノ粒子である<項1>に記載の組成物。
<項5>
前記磁性ナノ粒子は、アミン機能化Fe 3 O 4 ナノ粒子である<項4>に記載の組成物。
<項6>
前記アミン機能化Fe 3 O 4 ナノ粒子は、前記微細構造体のカルボキシル基と共有結合される<項5>に記載の組成物。
<項7>
前記微細構造体は、生体適合性ポリマースキャフォールドである<項1>に記載の組成物。
<項8>
前記生体適合性ポリマースキャフォールドは、多孔性スキャフォールドである<項7>に記載の組成物。
<項9>
前記生体適合性ポリマースキャフォールドは、ポリ乳酸−グリコール酸(PLGA)、ポリ乳酸(PLA)、ポリグリコール酸(PGA)、ポリビニルアルコール(PVA)、ポリエチレングリコール(PEG)、ポリ(N−2−ヒドロキシプロピルメタクリルアミド)、ポリヒドロキシアルカノン酸(PHA)、ポリカプロラクトン(PCL)、ポリ(プロピレンフマレート)、ポリアンヒドリド、ポリアセタール、またはポリカーボネート、ポリ(オルトエステル)から製造されたものである<項7>に記載の組成物。
<項10>
<項1>に記載の軟骨再生用組成物と、
軟骨欠損部位にX線を照射した後、前記軟骨再生用組成物及び患部をイメージングするための映像撮影部と、
前記軟骨再生用組成物を軟骨欠損部位に移動させる磁界生成部と
を含む、磁気駆動関節軟骨再生システム。
<項11>
前記磁界生成部は、コイル型または着用型である<項10>に記載の磁気駆動関節軟骨再生システム。
<項12>
前記磁界生成部は、電磁石または永久磁石により磁界生成される<項10>に記載の磁気駆動関節軟骨再生システム。
<項13>
前記永久磁石は、フェライト、ネオジム、アルニコ、サマリウムコバルトまたはゴム磁石である<項12>に記載の磁気駆動関節軟骨再生システム。
Claims (8)
- コラーゲン、ヒアルロン酸、ゼラチン、キトサン、PLGA{poly(lactic−co−glycolic acid)}、PGA{poly(glycolic acid)}、PLA{poly(lactic acid)} 及びPEG(poyethylene glycol)で構成された群から選択された生分解性ポリマーからなる多孔性微細構造体の表面にアミン基を有した生体適合性材料でアミン機能化された磁性ナノ粒子が付着された磁性多孔性微細構造体に軟骨生成細胞が付着された、磁性ナノ粒子及び軟骨生成細胞が付着された多孔性微細構造体を含む軟骨再生用組成物。
- 前記軟骨生成細胞は、軟骨細胞または幹細胞である請求項1に記載の組成物。
- 前記幹細胞は、骨髄由来幹細胞または脂肪由来幹細胞である請求項2に記載の組成物。
- 前記アミン機能化ナノ粒子は、前記微細構造体のカルボキシル基と共有結合される請求項1に記載の組成物。
- 請求項1に記載の軟骨再生用組成物と、
軟骨欠損部位にX線を照射した後、前記軟骨再生用組成物及び患部をイメージングするための映像撮影部と、
前記軟骨再生用組成物を軟骨欠損部位に移動させる磁界生成部と
を含む、磁気駆動関節軟骨再生システム。 - 前記磁界生成部は、コイル型または着用型である請求項5に記載の磁気駆動関節軟骨再生システム。
- 前記磁界生成部は、電磁石または永久磁石により磁界生成される請求項5に記載の磁気駆動関節軟骨再生システム。
- 前記永久磁石は、フェライト、ネオジム、アルニコ、サマリウムコバルトまたはゴム磁石である請求項7に記載の磁気駆動関節軟骨再生システム。
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US10507111B2 (en) * | 2018-03-09 | 2019-12-17 | Stephen Bramblett Johnson | Magnetic prosthetic |
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KR102315368B1 (ko) * | 2018-08-13 | 2021-10-20 | 재단법인대구경북과학기술원 | 자기장 구동 약물전달 마이크로 구조체 및 이의 제조방법 |
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KR102366335B1 (ko) * | 2019-03-29 | 2022-02-23 | 전남대학교산학협력단 | 조직재생용 성장인자 담지 다공성 마이크로스캐폴드 및 이의 제조방법 |
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KR102366334B1 (ko) * | 2019-03-29 | 2022-02-22 | 전남대학교산학협력단 | 자기 구동력이 증가된 조직재생용 다공성 마이크로스캐폴드 및 이의 제조방법 |
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