JP4717459B2 - 患者の組織の欠陥を修復するための組み合わせ移植片および組織の欠陥を修復する方法 - Google Patents
患者の組織の欠陥を修復するための組み合わせ移植片および組織の欠陥を修復する方法 Download PDFInfo
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- A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
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- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
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Description
小腸粘膜下組織(SIS)の組織スカホルドへのウシの切り刻まれた半月組織(BMT)の細胞の移住および新たな基質の形成が評価され比較された。半月組織は成体のウシの半月の白色および赤白色ゾーンから回収され、半月組織が切り刻まれて生存可能な組織の供給源が形成された。スカホルドが小腸粘膜下組織(SIS)から準備され、スリットがスカホルドに作られてポケットが形成された。切り刻まれた組織20mg/cm2 がスリットを通してSISスカホルド内に充填されて組み合わせ移植片が形成された。組み合わせ移植片はマウスのひとつの皮膚の切開部を通して半胸郭に形成されたポケット内に配置された。タッキング縫合糸5−0 Ethibond Excel(登録商標)が用いられて皮下への移住を防止するために皮膚を各組み合わせ移植片の周囲の筋系に取り付けた。
小腸粘膜下組織(SIS)の組織スカホルドへのウシの切り刻まれた半月組織(BMT)の細胞の移住および新たな基質の形成が評価され比較された。半月組織は成体のウシの半月の白色および赤白色ゾーンから回収され、半月組織が切り刻まれて生存可能な組織の供給源が形成された。スカホルドが小腸粘膜下組織(SIS)から準備され、スリットがスカホルドに作られてポケットが形成された。切り刻まれた組織が多血小板血漿(PRP)と組み合わされて、切り刻まれた組織とPRPの組み合わせ20mg/cm2 がスリットを通してSISスカホルド内に充填されて組み合わせ移植片が形成された。組み合わせ移植片はマウスのひとつの皮膚の切開部を通して半胸郭に形成されたポケット内に配置された。タッキング縫合糸5−0 Ethibond Excel(登録商標)が用いられて皮下への移住を防止するために皮膚を各組み合わせ移植片の周囲の筋系に取り付けた。
小腸粘膜下組織(SIS)の組織スカホルドへのウシの切り刻まれた半月組織(BMT)の細胞の移住および新たな基質の形成が評価され比較された。半月組織は成体のウシの半月の白色および赤白色ゾーンから回収され、半月組織が切り刻まれた。PRPが切り刻まれたBMTに加えられた。次に生存可能な組織の供給源がBMTおよびPRPを50:50の比率で生物再吸収性ポリマー製のスカホルド(「FPV」と呼ばれる。)と組み合わせることによって準備された。使用された生物再吸収性のスカホルドは不織繊維(PDS(ポリジオシサノン:Polydioxanone)およびビクリル(Vicryl)の混合物)で補強された凍結乾燥発泡スカホルド(65%のポリグリコール酸/35%のポリカプロラクトン)であった。スカホルドは小腸粘膜下組織(SIS)から準備され、スリットがスカホルドに作られてポケットが形成された。生存可能な組織の供給源であるFPV、BMT、およびPRPが20mg/cm2でスリットを通してSISスカホルド内に充填されて組み合わせ移植片が形成された。組み合わせ移植片はマウスのひとつの皮膚の切開部を通して半胸郭に形成されたポケット内に配置された。タッキング縫合糸5−0 Ethibond Excel(登録商標)が用いられて皮下への移住を防止するために皮膚を各組み合わせ移植片の周囲の筋系に取り付けた。
小腸粘膜下組織(SIS)の組織スカホルドへのウシの切り刻まれた軟骨組織(BCT)の細胞の移住および新たな基質の形成が評価され比較された。軟骨組織は成体のウシの大腿骨の関節顆から回収され、軟骨組織が切り刻まれた。PRPが切り刻まれたBCTに加えられた。次に生存可能な組織の供給源がBCTおよびPRPを50:50の比率で生物再吸収性ポリマー製のスカホルド(「PV」と呼ばれる。)と組み合わせることによって準備された。使用された生物再吸収性のスカホルドは不織布スカホルド(PDS(ポリジオシサノン:Polydioxanone)およびビクリル(Vicryl)の混合物)であった。スカホルドは小腸粘膜下組織(SIS)から準備され、スリットがスカホルドに作られてポケットが形成された。生存可能な組織の供給源であるPV、BCT、およびPRPが20mg/cm2でスリットを通してSISスカホルド内に充填されて組み合わせ移植片が形成された。組み合わせ移植片はマウスのひとつの皮膚の切開部を通して半胸郭に形成されたポケット内に配置された。タッキング縫合糸5−0 Ethibond Excel(登録商標)が用いられて皮下への移住を防止するために皮膚を各組み合わせ移植片の周囲の筋系に取り付けた。
組織スカホルドに移住する在来の半月の細胞に対する生物活性物質を使用することの効果が評価された。半月がウシの膝から回収されて、4mmの外植片が白色および赤白色領域から取り出された。2mmのパンチ生検がスカホルドを挿入する前に外植片の中央から取り除かれた。直径2mmの生物再吸収性の発泡スカホルド(60%のポリ乳酸および40%のポリカプロラクトン)が血液、多血小板血漿(PRP)、または8倍の濃縮PRPで処理され、外植片の中央に挿入された。スカホルドが挿入された外植片が一日おきに培地を交換して標準的な細胞培養条件の下で2週間および3週間に亘って培養された。2週間および3週間の時点で、外植片内のスカホルドが取り除かれて、細胞の個数がシクワント(CyQuant)検定を用いてDNAの量によって見積もられた。
組織スカホルドに移住する在来の細胞に対する生物活性物質を使用することの効果が評価された。半月がウシの膝から回収されて、4mmの外植片が白色および赤白色領域から取り出された。2mmのパンチ生検がスカホルドを挿入する前に外植片の中央から取り除かれた。PDS(ポリジオキサノン)メッシュで補強された直径2mmの生物再吸収性の発泡スカホルド(65%のポリグリコール酸および35%のポリカプロラクトン)が濃度10ng/ml、濃度100ng/ml、および濃度300ng/mlの100μlのCDMP−1中に浸漬された。スカホルドが一晩に亘って凍結乾燥されて成長因子がスカホルド内で凍結乾燥され、スカホルドが外植片の中央に挿入された。スカホルドが挿入された外植片が一日おきに培地を交換して標準的な細胞培養条件の下で3週間に亘って培養された。2週間および3週間の時点で、外植片内のスカホルドが取り除かれて、細胞の個数がシクワント(CyQuant)検定を用いてDNAの量によって見積もられた。
組織スカホルドに移住する在来の細胞に対する生物活性物質を使用することの効果が評価された。半月がウシの膝から回収されて、4mmの外植片が白色および赤白色領域から取り出された。2mmのパンチ生検がスカホルドを挿入する前に外植片の中央から取り除かれた。PDS(ポリジオキサノン)メッシュで補強された直径2mmの生物再吸収性の発泡スカホルド(65%のポリグリコール酸および35%のポリカプロラクトン)が濃度150ng/mlの100μlのCDMP−1中に浸漬された。スカホルドが一晩に亘って凍結乾燥されて成長因子がスカホルド内で凍結乾燥され、スカホルドが外植片の中央に挿入された。スカホルドが挿入された外植片が一日おきに培地を交換して標準的な細胞培養条件の下で3週間に亘って培養された。3週間の時点で、外植片が取り除かれて、ヘマトキシリン−エオシン(H/E)で染色するために組織学的に処理された。
(1)患者の組織の欠陥を修復するための組み合わせ移植片であって、
生物再吸収性の合成ポリマー材料から作られていて生存可能な組織を収容するように適合された少なくともひとつのポケットが形成された多孔性の組織スカホルドを有する、組み合わせ移植片。
(2)組織スカホルドの少なくともひとつのポケット内に配置され上記組織スカホルド内に移住して上記組織スカホルドを取り囲む在来の組織と一体化するのに有効な生存可能な組織をさらに有する、上記実施態様(1)記載の組み合わせ移植片。
(3)生存可能な組織に適用されていて細胞の成長を活発にするのに有効な少なくともひとつの生物活性物質をさらに有する、上記実施態様(2)記載の組み合わせ移植片。
(4)生物活性物質が、血餅、多血小板血漿、軟骨由来の形態発生たんぱく、組み換え型のヒト成長因子、およびそれらの組み合わせからなる集合から選択される、上記実施態様(3)記載の組み合わせ移植片。
(5)組織スカホルドが上部部分および底部部分を含む、上記実施態様(1)記載の組み合わせ移植片。
(7)組織スカホルドの上部部分および底部部分が上記上部部分および上記底部部分の周縁部で互いに熱融着されて上記上部部分および上記底部部分の間に閉じたポケットが形成されている、上記実施態様(5)記載の組み合わせ移植片。
(8)閉じたポケット内に配置された生存可能な組織をさらに有する、上記実施態様(7)記載の組み合わせ移植片。
(9)組織スカホルドが実質的に楔形の形状を有し、ポケットが上記組織スカホルドに形成された中空内部からなる、上記実施態様(1)記載の組み合わせ移植片。
(10)組織スカホルドが実質的に楔形の形状を有し、ポケットが上記組織スカホルド内に延在する少なくともひとつの内腔からなる、上記実施態様(1)記載の組み合わせ移植片。
(12)少なくともひとつの表面特徴部が組織スカホルドの外側面に形成された複数のチャネルからなる、上記実施態様(11)記載の組み合わせ移植片。
(13)患者の組織の欠陥を修復するための組み合わせ移植片であって、
少なくともひとつのポケットが形成された多孔性の組織スカホルドと、
上記組織スカホルドの上記少なくともひとつのポケット内に配置され上記組織スカホルド内に移住して上記組織スカホルドを取り囲む在来の組織と一体化するのに有効で、切り刻まれた組織の破片、スライスされた組織の破片、および細長く切られた組織の破片からなる集合から選択された生存可能な組織と
を有する、組み合わせ移植片。
(14)組織スカホルドが、天然ポリマー、合成ポリマー、およびそれらの組み合わせからなる集合から選択された少なくともひとつの材料から作られている、上記実施態様(13)記載の組み合わせ移植片。
(15)生存可能な組織に適用されていて細胞の成長を活発にするのに有効な少なくともひとつの生物活性物質をさらに有する、上記実施態様(13)記載の組み合わせ移植片。
(17)組織スカホルドが上部部分および底部部分を含む、上記実施態様(13)記載の組み合わせ移植片。
(18)上部部分および底部部分が少なくとも部分的に結合されている、上記実施態様(17)記載の組み合わせ移植片。
(19)組織スカホルドの上部部分および底部部分が上記上部部分および上記底部部分の周縁部で互いに熱融着されて上記上部部分および上記底部部分の間に生存可能な組織を収容する閉じたポケットが形成されている、上記実施態様(17)記載の組み合わせ移植片。
(20)組織スカホルドが実質的に楔形の形状を有し、ポケットが上記組織スカホルドに形成された中空内部からなる、上記実施態様(13)記載の組み合わせ移植片。
(22)組織スカホルドが血管の形成を促進するために形成された少なくともひとつの表面特徴部を含む、上記実施態様(13)記載の組み合わせ移植片。
(23)少なくともひとつの表面特徴部が組織スカホルドの外側面に形成された複数のチャネルからなる、上記実施態様(22)記載の組み合わせ移植片。
(24)組織の欠陥を修復する方法であって、
生物再吸収性の合成ポリマー材料から作られていて生存可能な組織を収容するように適合された少なくともひとつのポケットが形成された組織スカホルドを提供する過程と、
上記生存可能な組織を得る過程と、
上記組織スカホルドの上記少なくともひとつのポケット内に上記生存可能な組織を装填する過程と、
上記生存可能な組織が配置された上記組織スカホルドを患者の体の欠陥部位に植え込む過程と
を有する、組織の欠陥を修復する方法。
(25)細胞の成長を促進するために少なくともひとつの生物活性物質を生存可能な組織に適用する過程をさらに有する、上記実施態様(24)記載の方法。
(27)組織スカホルドが上部部分および底部部分を含む、上記実施態様(24)記載の方法。
(28)上部部分および底部部分が少なくとも部分的に結合されている、上記実施態様(27)記載の方法。
(29)組織スカホルドの上部部分および底部部分が上記上部部分および上記底部部分の周縁部で互いに熱融着されて上記上部部分および上記底部部分の間に生存可能な組織を収容する閉じたポケットが形成されている、上記実施態様(27)記載の方法。
(30)組織スカホルドが実質的に楔形の形状を有し、ポケットが上記組織スカホルドに形成された中空内部からなる、上記実施態様(24)記載の方法。
(32)組織スカホルドが血管の形成を促進するために形成された少なくともひとつの表面特徴部を含む、上記実施態様(24)記載の方法。
(33)少なくともひとつの表面特徴部が組織スカホルドの外側面に形成された複数のチャネルからなる、上記実施態様(32)記載の方法。
(34)組織の欠陥を修復する方法であって、
生存可能な組織を収容するように適合された少なくともひとつのポケットが形成された組織スカホルドを提供する過程と、
上記生存可能な組織を得る過程と、
上記生存可能な組織を準備して、切り刻まれた組織の破片、スライスされた組織の破片、および細長く切られた組織の破片からなる集合から選択された組織の破片を形成する過程と、
上記組織スカホルドの上記少なくともひとつのポケット内に上記組織の破片を装填する過程と、
上記組織の破片が配置された上記組織スカホルドを患者の体の欠陥部位に植え込む過程と
を有する、組織の欠陥を修復する方法。
(35)組織スカホルドが、天然ポリマー、合成ポリマー、およびそれらの組み合わせからなる集合から選択された少なくともひとつの材料から作られている、上記実施態様(34)記載の方法。
(37)生物活性物質が、血餅、多血小板血漿、軟骨由来の形態発生たんぱく、組み換え型のヒト成長因子、およびそれらの組み合わせからなる集合から選択される、上記実施態様(36)記載の方法。
(38)組織スカホルドが実質的に楔形の形状を有し、ポケットが上記組織スカホルドに形成された中空内部からなる、上記実施態様(34)記載の方法。
(39)組織スカホルドが実質的に楔形の形状を有し、ポケットが上記組織スカホルド内に延在する少なくともひとつの内腔からなる、上記実施態様(34)記載の方法。
(40)組織スカホルドが血管の形成を促進するために形成された少なくともひとつの表面特徴部を含む、上記実施態様(34)記載の方法。
(41)少なくともひとつの表面特徴部が組織スカホルドの外側面に形成された複数のチャネルからなる、上記実施態様(40)記載の方法。
12 組織スカホルド
12a 上部壁
12b 底部壁
12c 側面壁
12d 側面壁
12e 端部壁
14 ポケット
16 生存可能な組織
20 組み合わせ移植片
22 組織スカホルド
22a 上部壁
22b 底部壁
22c 側面壁
22d 側面壁
22e 端部壁
24 ポケット
26 生存可能な組織
30 組み合わせ移植片
32 組織スカホルド
32a 上部部分
32b 底部部分
34 ポケット
36 生存可能な組織
40 組み合わせ移植片
42 組織スカホルド
42a 上部層
42b 底部層
44 ポケット
46 生存可能な組織
50 組み合わせ移植片
52 組織スカホルド
52a 上部層
52b 底部層
54 ポケット
56 生存可能な組織
60 移植片
62 組織スカホルド
62a 上部部分
62b 底部部分
64 ポケット
66 生存可能な組織
68 チャネル
70 移植片
72 組織スカホルド
72a 上部部分
72b 底部部分
74 ポケット
76 生存可能な組織
78 ボア
80a 対照の組織スカホルド
80d FPVスカホルド
80e 組織スカホルド80e
82b BMT
82c BMTおよびPRP
82d BMTおよびPRPの組織の供給源
82e 生存可能な組織の供給源
84b 在来の半月組織の細胞
84c 在来の半月組織の細胞
84d 在来の半月組織の細胞
84e 在来の軟骨組織の細胞
100 熱融着装置
102a 上側部材
102b 下側トレー
104 ヒンジ
Claims (27)
- 患者の組織の欠陥を修復するための組み合わせ移植片であって、
生物再吸収性の合成ポリマー材料から作られていて生存可能な組織を収容するように適合された少なくともひとつのポケットが形成された多孔性の楔形組織スカホルドを有し、
前記生存可能な組織が前記スカホルドに移住可能な在来の組織からの細胞および前記細胞の細胞外基質を含み、前記生存可能な組織は、細かく切り刻まれた組織の破片の形態である、組み合わせ移植片。 - 前記生存可能な組織に適用されていて細胞の成長を活発にするのに有効な少なくともひとつの生物活性物質をさらに有する、請求項1記載の組み合わせ移植片。
- 前記生物活性物質が、血餅、多血小板血漿、軟骨由来の形態発生たんぱく、組み換え型のヒト成長因子、およびそれらの組み合わせからなる集合から選択される、請求項2記載の組み合わせ移植片。
- 前記組織スカホルドが上部部分および底部部分を含む、請求項1記載の組み合わせ移植片。
- 前記上部部分および前記底部部分が少なくとも部分的に結合されている、請求項4記載の組み合わせ移植片。
- 前記組織スカホルドの前記上部部分および前記底部部分が前記上部部分および前記底部部分の周縁部で互いに熱融着されて前記上部部分および前記底部部分の間に閉じたポケットが形成されている、請求項4記載の組み合わせ移植片。
- 前記ポケットが前記組織スカホルドに形成された中空内部からなる、請求項1記載の組み合わせ移植片。
- 前記ポケットが前記組織スカホルド内に延在する少なくともひとつの内腔からなる、請求項1記載の組み合わせ移植片。
- 前記組織スカホルドが血管の形成を促進するために形成された少なくともひとつの表面特徴部を含む、請求項1記載の組み合わせ移植片。
- 少なくともひとつの前記表面特徴部が前記組織スカホルドの外側面に形成された複数のチャネルからなる、請求項9記載の組み合わせ移植片。
- 患者の組織の欠陥を修復するための組み合わせ移植片であって、
少なくともひとつのポケットが形成された多孔性の楔形組織スカホルドと、
上記組織スカホルドの上記少なくともひとつのポケット内に配置され上記組織スカホルド内に移住して上記組織スカホルドを取り囲む在来の組織と一体化するのに有効な生存可能な組織であって、前記生存可能な組織が前記在来の組織からの細胞および前記細胞の細胞外基質を含み、細かく切り刻まれた組織の破片の形態である生存可能な組織と
を有する、組み合わせ移植片。 - 前記組織スカホルドが、天然ポリマー、合成ポリマー、およびそれらの組み合わせからなる集合から選択された少なくともひとつの材料から作られている、請求項11記載の組み合わせ移植片。
- 前記生存可能な組織に適用されていて細胞の成長を活発にするのに有効な少なくともひとつの生物活性物質をさらに有する、請求項11記載の組み合わせ移植片。
- 前記生物活性物質が、血餅、多血小板血漿、軟骨由来の形態発生たんぱく、組み換え型のヒト成長因子、およびそれらの組み合わせからなる集合から選択される、請求項13記載の組み合わせ移植片。
- 前記組織スカホルドが上部部分および底部部分を含む、請求項11記載の組み合わせ移植片。
- 前記上部部分および前記底部部分が少なくとも部分的に結合されている、請求項15記載の組み合わせ移植片。
- 前記組織スカホルドの前記上部部分および前記底部部分が前記上部部分および前記底部部分の周縁部で互いに熱融着されて前記上部部分および前記底部部分の間に前記生存可能な組織を収容する閉じたポケットが形成されている、請求項15記載の組み合わせ移植片。
- 前記ポケットが上記組織スカホルドに形成された中空内部からなる、請求項11記載の組み合わせ移植片。
- 前記ポケットが上記組織スカホルド内に延在する少なくともひとつの内腔からなる、請求項11記載の組み合わせ移植片。
- 前記組織スカホルドが血管の形成を促進するために形成された少なくともひとつの表面特徴部を含む、請求項11記載の組み合わせ移植片。
- 少なくともひとつの前記表面特徴部が前記組織スカホルドの外側面に形成された複数のチャネルからなる、請求項20記載の組み合わせ移植片。
- 前記組織スカホルドの前記ポケット内の前記生存可能な組織からの細胞が前記組織スカホルドの少なくとも一部で増殖する、請求項1記載の組み合わせ移植片。
- 前記在来の組織からの細胞が前記組織スカホルドの少なくとも一部で増殖する、請求項1記載の組み合わせ移植片。
- 前記組織の破片の厚みが200μmから3mmまでの範囲にある、請求項11記載の組み合わせ移植片。
- 前記組織の破片の粒子サイズが0.5mm3から3mm3までの範囲にある、請求項11記載の組み合わせ移植片。
- 前記組織スカホルドの前記ポケット内の前記生存可能な組織からの細胞が前記組織スカホルドの少なくとも一部で増殖する、請求項11記載の組み合わせ移植片。
- 前記在来の組織からの細胞が前記組織スカホルドの少なくとも一部で増殖する、請求項11記載の組み合わせ移植片。
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US10/775,034 US11395865B2 (en) | 2004-02-09 | 2004-02-09 | Scaffolds with viable tissue |
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US20220331491A1 (en) | 2022-10-20 |
EP1561481B1 (en) | 2012-03-28 |
US11395865B2 (en) | 2022-07-26 |
CA2496184A1 (en) | 2005-08-09 |
AU2005200305A1 (en) | 2005-08-25 |
CA2496184C (en) | 2012-04-24 |
EP1561481A2 (en) | 2005-08-10 |
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US20050177249A1 (en) | 2005-08-11 |
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