43 Ìèíè-îáçîðû Ñèíòåòè÷åñêèå áèîìàòåðèàëû íà îñíîâå ïîëèìåðîâ îðãàíè÷åñêèõ êèñëîò â òêàíåâîé èíæåíåðèè À.Â. Âîëêîâ  ïîñëåäíåå âðåìÿ âñå áîëüøèìè òåìïàìè èäåò ðàçâèòèå áèîòåõíîëîãèé, â òîì ÷èñëå è ìåäèöèíñêîé áèîòåõíîëîãèè. Èçó÷åíèå ìåõàíèçìîâ ðåãåíåðàöèè òêàíåé è îðãàíîâ, ïîèñê íîâûõ òåõíîëîãèé, êîòîðûå ìîãëè áû âîññòàíîâèòü óòðà÷åííóþ ôóíêöèþ êàêîãî ëèáî îðãàíà èëè ñèñòåìû, ïðèâåëè ê ïîÿâëåíèþ íîâûõ îòðàñëåé, âîçíèêøèõ íà ñòûêå áèîòåõíîëîãèè è ìåäèöèíû òêàíåâîé èíæåíåðèè, ðåãåíåðàòèâíîé ìåäèöèíû è îðãàíîãåíåçà. Ýòè íàóêè èçó÷àþò ñîçäàíèå îðãàíîâ è òêàíåé de novo.  èõ îñíîâå ëåæèò ïðèíöèï òðàíñïëàíòàöèè êëåòîê íà ìàòðèöàõ-íîñèòåëÿõ. Ìàòðèöà-íîñèòåëü èëè ìàòðèêñ ïðåäñòàâëÿåò ñîáîé ñèíòåòè÷åñêèé èëè áèîëîãè÷åñêèé êîìïëåêñ äëÿ îáåñïå÷åíèÿ ìåõàíè÷åñêîé ïðî÷íîñòè êîíñòðóêöèè ñ çàäàííûìè ñâîéñòâàìè, òðåõìåðíîãî îðèåíòèðîâàíèÿ íàíåñåííîé íà íåãî êëåòî÷íîé êóëüòóðû. Îñíîâíûìè êðèòåðèÿìè áèîëîãè÷åñêè ñîâìåñòèìîé ìàòðèöû äëÿ ñîçäàíèÿ òêàíåèíæåíåðíîé êîíñòðóêöèè äîëæíû áûòü: îòñóòñòâèå öèòîòîêñè÷íîñòè, ïîääåðæàíèå àäãåçèè, ôèêñàöèè, ïðîëèôåðàöèè è äèôôåðåíöèðîâêè, ïîìåùåííûõ íà åå ïîâåðõíîñòü êëåòîê, îòñóòñòâèå ýôôåêòà ïîääåðæàíèÿ âîñïàëåíèÿ, â òîì ÷èñëå èììóííîãî, äîñòàòî÷íàÿ ìåõàíè÷åñêàÿ ïðî÷íîñòü â ñîîòâåòñòâèè ñ íàçíà÷åíèåì, áèîðåçîðáèðóåìîñòü îáû÷íûìè ìåòàáîëè÷åñêèìè ïóòÿìè, íàïðèìåð, ôåðìåíòàòèâíûì èëè ãèäðîëèçîì [1, 4-10, 15-18, 20, 22, 25-27]. Îäíèìè èç ïåðâûõ ìàòåðèàëîâ äëÿ òêàíåâîé èíæåíåðèè ñòàëè áèîäåãðàäèðóåìûå ñèíòåòè÷åñêèå áèîìàòåðèàëû íà îñíîâå ïîëèìåðîâ îðãàíè÷åñêèõ êèñëîò. Áëàãîäàðÿ ñâîèì õèìè÷åñêèì è ôèçè÷åñêèì ñâîéñòâàì îíè ïîçâîëÿþò ïîëó÷àòü èç íèõ øèðîêèé ñïåêòð êîíñòðóêöèé, òàêèõ, êàê ñåòêè, ïîðèñòûå ìàòðèöû, ïëåíêè è íåòêàíûå ìàòåðèàëû. Ñåò÷àòûå êîíñòðóêöèè â îñíîâíîì èñïîëüçóþòñÿ êàê àðìèðóþùèé ìàòåðèàë â êîìáèíèðîâàííûõ ãðàôòàõ, òàê êàê áîëüøèå â äèàìåòðå íèòè íå ïîçâîëÿþò êóëüòèâèðîâàòü íà íèõ íåîáõîäèìîå êîëè÷åñòâî êëåòîê. Îíè ìîãóò ðàçìåùàòüñÿ ñ áîëüøåé èëè ìåíüøåé ïëîòíîñòüþ òîëüêî â óçëàõ ðåøåòêè, ÷òî íåäîñòàòî÷íî äëÿ ïðåñëåäóåìûõ èññëåäîâàòåëåì öåëåé. Íåòêàíûå ìàòåðèàëû ïðåäñòàâëÿþò ñîáîé ìàòåðèàë, ñõîäíûé ïî ñòðóêòóðå ñ âàòîé, òîíêèå íèòè, ïåðåïëåòåííûå ìåæäó ñîáîé, îáåñïå÷èâàþò äîñòàòî÷íóþ ïðî÷íîñòü è ôèêñàöèþ êëåòîê â 3D ïðîñòðàíñòâå. Ïîðèñòûå ìàòåðèàëû ïîëó÷àþò ñìåøèâàíèåì ïîëèìåðîâ ñ òàê íàçûâàåìûìè ïîðîãåíàìè âåùåñòâàìè, êîòîðûå âûìûâàþòñÿ èíûìè, ÷åì ïîëèìåð, ðàñòâîðèòåëÿìè, íàïðèìåð, NaCl è âîäà. PGA, ðàñòâîðåííûé â ñâîåì ðàñòâîðèòåëå (õëîðîôîðì), ñîåäèíÿåòñÿ ñ íóæíûìè ïî ðàçìåðó êðèñòàëëàìè ñîëè. Ïîñëå òîãî, êàê óëåòó÷èâàåòñÿ õëîðîôîðì è çàòâåðäåâàåò ïîëèìåð, åãî îïóñêàþò â ðàñòâîðèòåëü äëÿ ïîðîãåíà (âîäó). Âîäà ðàñòâîðÿåò ñîëü è â ìåñòàõ ïðèñóòñòâèÿ êðèñòàëëîâ îáðàçóþòñÿ ïîðû. Ïîðèñòûå ìàòåðèàëû ïîäõîäÿò äëÿ ïîëó÷åíèÿ ýêâèâàëåíòîâ òàêèõ òêàíåé, êàê êîñòíàÿ è õðÿùåâàÿ. Ïëåíêè èç ïîëèìåðîâ îðãàíè÷åñêèõ êèñëîò ïîçâîëÿþò ïîëó÷èòü ëèøü 2D êîíñòðóêöèè, êîòîðûå ìîãóò áûòü èñïîëüçîâàíû è äëÿ ñîçäàíèÿ ýêâèâàëåíòîâ ýïèòåëèàëüíûõ òêàíåé è êàê àðìèðóþùèé ýëåìåíò. Áèîäåãðàäèðóåìûå ïîëèýñòåðû ñåìåéñòâî áèîäåãðàäèðóåìûõ ìàòåðèàëîâ, ñîñòîÿùèõ èç öåïè ïîâòîðÿþùèõñÿ îñòàòêîâ êîðîòêîöåïî÷å÷íûõ îðãàíè÷åñêèõ êèñëîò, òàêèõ, êàê ìîëî÷íàÿ è ãëèêîëåëèåâàÿ.  ñîñòàâ ïîëèìåðà ìîæåò âõî- äèòü êàê îäèí òèï êèñëîòíîãî îñòàòêà - PGA, PLA, òàê è èõ ñî÷åòàíèå â ðàçëè÷íûõ ïðîïîðöèÿõ, íàïðèìåð PGLA 30/70.  ìåäèöèíñêîé ïðàêòèêå ýòè ïîëèìåðû íàøëè øèðîêîå ïðèìåíåíèå â âèäå øîâíîãî ìàòåðèàëà, àðìèðóþùèõ êîíñòðóêöèé, ñåòîê äëÿ ãåðìèíîïëàñòèêè. Ïåðâûì êîììåð÷åñêèì ïðîäóêòîì áûë øîâíûé ìàòåðèàë ïîä íàçâàíèåì Dexon TM è Vicryl (American Cyanamid Co.). PGA - òâåðäûé, òåðìîïëàñòè÷íûé ìàòåðèàë, òåìïåðàòóðà ïëàâëåíèÿ 225 ãðàäóñîâ. Áëàãîäàðÿ âûñîêîé êðèñòàëëè÷íîñòè (40-50%) îí íå ðàñòâîðèì â áîëüøèíñòâå îðãàíè÷åñêèõ ðàñòâîðèòåëåé. Áèîäåãðàäàöèÿ ïîëèìåðà ïðîèñõîäèò ïóòåì ãèäðîëèçà äî óãëåêèñëîãî ãàçà è âîäû (ðèñ. 1), ñ íåêîòîðûì ïîâûøåíèåì pH îêðóæàþùèõ òêàíåé [11], à òàêæå âûâîäèòñÿ â âèäå ìîíîìåðà. Ìåõàíè÷åñêàÿ ïðî÷íîñòü ñîõðàíÿåòñÿ ìàêñèìóì äî 21 29 äíÿ, ñ ïîòåðåé ìàññû äî 40% ê ýòîìó ïåðèîäó. Ìàòåðèàë íå îáëàäàåò öèòîòîêñè÷åñêèìè ñâîéñòâàìè, ïîääåðæèâàåò àäãåçèþ è ïðîëèôåðàöèþ êëåòîê, à òàêæå â íåêîòîðîé ñòåïåíè îáëàäàåò îñòåîèíäóêòèâíûìè ñâîéñòâàìè. Èç ýòîãî ìàòåðèàëà ìîãóò áûòü èçãîòîâëåíû ìàòðèöû ðàçëè÷íîé ñòðóêòóðíîé îðãàíèçàöèè (ðèñ. 2, 3). Ðèñ. 1. Ñõåìà ãèäðîëèçà PGLA. Ïðîäóêòû ãèäðîëèçà íå òîêñè÷íû è ó÷àñòâóþò â öèêëå Êðåáñà ñ îáðàçîâàíèåì óãëåêèñëîãî ãàçà è âîäû Ñåìåéñòâî PLA âêëþ÷àåò ïîëèìåðû èç îñòàòêîâ ìîëî÷íîé êèñëîòû, ïðåäñòàâëåíî öåëîé ïëåÿäîé ïðîäóêòîâ, îòëè÷àþùèõñÿ ñâîèìè ñâîéñòâàìè, áëàãîäàðÿ èçîôîðìàì è êîëè÷åñòâó ìîëåêóë â ïîëèìåðå (òàáë. 1). Ïî ñâîèì õèìè÷åñêèì, ôèçè÷åñêèì è áèîëîãè÷åñêèì ñâîéñòâàì ýòîò ïîëèìåð áëèçîê ê PGA, îäíàêî óñòóïàåò åìó â ïðî÷íîñòè è ñêîðîñòè ãèäðîëèçíîé ðåçîðáöèè, êîòîðàÿ ó íåãî íèæå. Ðèñ. 2. Âîëîêíèñòàÿ (íåòêàíàÿ) ìàòðèöà èç PGA. Ñêàíèðóþùàÿ ýëåêòðîííàÿ ìèêðîñêîïèÿ (ÑÝÌ) Ðèñ. 3. Ãóá÷àòàÿ ìàòðèöà èç PLA. ÑÝÌ Êëåòî÷íàÿ òðàíñïëàíòîëîãèÿ è òêàíåâàÿ èíæåíåðèÿ ¹ 2, 2005 44 Ìèíè-îáçîðû Íàèëó÷øèìè æå ïîêàçàòåëÿìè îáëàäàþò ñîïîëèìåðû PGA è PLA (PDLA) PGLA (PGDLA).  çàâèñèìîñòè îò ïðîöåíòíîãî ñîîòíîøåíèÿ ìîëî÷íîé è êëèêîëåâîé êèñëîò ìîæíî ìåíÿòü ñâîéñòâà ïðîäóêòà, íàïðèìåð, ïëàñòè÷íîñòü, ïðî÷íîñòü, ñðîê áèîäåãðàäàöèè è äð.  òå÷åíèå äëèòåëüíîãî âðåìåíè ïðîèçâîäèëîñü òåñòèðîâàíèå ýòèõ ïîëèìåðîâ ñ ðàçëè÷íûìè òèïàìè êëåòîê. Áûëî óñòàíîâëåíî, ÷òî äàííûå ìàòåðèàëû ìîãóò ñëóæèòü ìàòðèöåé äëÿ ñîçäàíèÿ òêàíåèíæåíåðíûõ êîíñòðóêöèé ìûøå÷íîé, õðÿùåâîé, êîñòíîé è ýïèòåëèàëüíîé òêàíåé. Îñîáîå ìåñòî ïîëèìåðû íà îñíîâå ìîëî÷íîé è êëèêîëåâîé êèñëîò çàíÿëè â ðåêîíñòðóêòèâíîé õèðóðãèè è ðåãåíåðàòèâíîé ìåäèöèíå. Îíè èñïîëüçóþòñÿ äëÿ âîññòàíîâëåíèÿ äåôåêòîâ êîñòíîé è õðÿùåâîé òêàíè â êëèíè÷åñêîé ïðàêòèêå [1, 6-10, 15, 19, 25-27] è áûëè îäîáðåíû FDA (Àãåíòñòâîì ïî êîíòðîëþ çà ëåêàðñòâàìè è ïðîäóêòàìè ïèòàíèÿ ÑØÀ) êàê áåçîïàñíûå ìàòåðèàëû äëÿ òêàíåâîé èíæåíåðèè [28]. Ïîëèêàïðîëàêòîí (PCL) åùå îäèí ïðåäñòàâèòåëü ñåìåéñòâà ïîëèýñòåðîâ (ðèñ. 4). Ïîëóïðîçðà÷íûé ïîëèìåð ñ òåìïåðàòóðîé ïëàâëåíèÿ ìåíåå 60 ãðàäóñîâ (ñì. òàáë. 1). Ñðîê áèîäåãðàäàöèè ñîñòàâëÿåò îêîëî 3 Ðèñ. 4. Ôîðìóëà PCL ëåò. Ýòè ñâîéñòâà ïîçâîëÿþò ïîëó÷àòü äîñòàòî÷íî ïëàñòè÷íûå êîíñòðóêöèè, îáåñïå÷èâàþùèå äëèòåëüíóþ ìåõàíè÷åñêóþ ïðî÷íîñòü è ïîääåðæêó. Êðîìå òîãî, ïîëèìåð îáëàäàåò îò÷åòëèâûìè îñòåîèíäóêòèâíûìè ñâîéñòâàìè, è íà íåì áåñïðåïÿòñòâåííî àäãåçèðóþòñÿ ìàëîäèôôåðåíöèðîâàííûå ìåçåíõèìàëüíûå êëåòêè (ðèñ. 5). Êîììåð÷åñêèé ïðåïàðàò, ïðèìåíÿåìûé â çäðàâîîõðàíåíèè, MONOCRYL, Ethicon Inc. øîâíûé ìàòåðèàë äëÿ õèðóðãèè. Ðèñ. 5. Ôèáðîáëàñòîïîäîáíûå êëåòêè, àäãåçèðîâàâøèå â óñëîâèÿõ êóëüòóðû ê ãðàíóëàì êàïðîëàêòîíà (À) è ê ïîðèñòîìó êàïðîëàêòîíó (Â). ÑÝÌ Òàáëèöà 1. Ñâîéñòâà áèîäåãðàäèðóåìûõ ïîëèìåðîâ Ïîëèìåð Òåìïåðàòóðíûå è ìåõàíè÷åñêèå ñâîéñòâà t ïëàâëåíèÿ (°C) ëèçàöèè (°C) ïðî÷íîñòü Âðåìÿ äåãðàäàöèè (ìåñÿöû) t êðèñòàë- Ïðîäóêòû äåãðàäàöèè Ïðèìå÷àíèÿ Poly(glycolic acid), PGA 225230 3540 7,0 GPa 62 Glycolic acid, CO2, H2O Poly(l-lactic acid), PLLA 173178 6065 2,7 GPa >24 l-lactic acid, CO2, H2O Poly(d,l-lactic acid), PLDA Àìîðôíûé 5560 1,9 GPa 1216 d,l-lactic acid, CO2, H2O Poly(d,l-lactic-co-glycolic acid)(85/15), PDLGA85/15 Àìîðôíûé 5055 2,0 GPa 56 d,l-lactic acid b glycolic acid, CO2, H2O Poly(d,l-lactic-co-glycolic acid)(85/15), PDLGA85/15 Àìîðôíûé 5055 2,0 GPa 45 d,l-lactic acid è glycolic acid, CO2, H2O Poly(d,l-lactic-co-glycolic acid)(85/15), PDLGA85/15 Àìîðôíûé 4550 2,0 GPa 34 d,l-lactic acid è glycolic acid, CO2, H2O Poly(d,l-lactic-co-glycolic acid)(85/15), PDLGA85/15 Àìîðôíûé 4550 2,0 GPa I2 d,l-lactic acid è glycolic acid, CO2, H2O Poly(capro- lactone), PCL 5863 6065 0,4 GPa >24 Caproic acid, CO2, H2O Òêàíåñîâìåñòèìûé ïîëèìåð ñ íèçêîé öèòîòîêñè÷íîñòüþ Poly(propylene fumarate) Fumaric acid, propylene glycol è poly(acrylic acidco-fumaric acid) Âûçûâàåò óìåðåííûå ìåñòíûå âîñïàëèòåëüíûå ðåàêöèè, ðåàêöèþ íà èíîðîäíîå òåëî, ôèáðîç Êëåòî÷íàÿ òðàíñïëàíòîëîãèÿ è òêàíåâàÿ èíæåíåðèÿ ¹ 2, 2005 230 MPa  çàâèñèìîñòè îò ôîðìóëû, ìîæåò äîñòèãàòü íåñêîëüêî ìåñÿöåâ Áîëüøîå êîëè÷åñòâî èññëåäîâàíèé ïîêàçàëè, ÷òî äàííûå ïðåïàðàòû íå èìåþò âûðàæåííîé öèòîòîêñè÷íîñòè, õîòÿ è ñíèæàþò ðÍ ñðåäû âî âðåìÿ ãèäðîëèçà. Ïðåèìóùåñòâî ïîëíûé ãèäðîëèç äî óãëåêèñëîãî ãàçà è âîäû, îáû÷íûìè ìåòàáîëè÷åñêèìè ïóòÿìè Ìèíè-îáçîðû Ïîëèïðîïèëåí ôóìàðàò äîñòàòî÷íî ïðî÷íûé, ïëàñòè÷íûé ïîëèìåð, òàêæå ïðåäíàçíà÷åííûé äëÿ äëèòåëüíîé ïîääåðæêè ìåõàíè÷åñêîé ïðî÷íîñòè êîíñòðóêöèè â òå÷åíèå êàê ìèíèìóì 200 äíåé. Áèîäåãðàäàöèÿ ïðîèñõîäèò ôåðìåíòàòèâíûì ãèäðîëèçíûì ïóòåì, íî, â îòëè÷èå îò ïðåäûäóùèõ ìàòåðèàëîâ, íå âëèÿåò íà pH îêðóæàþùèõ òêàíåé ïðè áèîäåãðàäàöèè. Ê ñóùåñòâåííûì íåäîñòàòêàì ìîæíî îòíåñòè îáðàçîâàíèå ôèáðîçíîé êàïñóëû êàê îòâåò íà èíîðîäíîå òåëî, ÷òî îêàçûâàåòñÿ íåáëàãîïðèÿòíûì â ðÿäå ñèòóàöèé [12, 14]. Òàêèì îáðàçîì, â íàñòîÿùåì îáçîðå ïðåäñòàâëåíû îñíîâíûå ðàçíîâèäíîñòè îðãàíè÷åñêèõ ïîëèìåðíûõ áèîäåãðàäèðóåìûõ ìàòåðèàëîâ äëÿ òêàíåâîé èíæåíåðèè. Íàèáîëåå ÿðêèìè ïðåäñòàâèòåëÿìè, çàðåêîìåíäîâàâøèìè ñåáÿ êàê â ýêñïåðèìåíòàëüíûõ, òàê è â êëèíè÷åñêèõ èññëåäîâàíèÿõ, ÿâëÿþòñÿ ïîëèýôèðû ìîëî÷íîé è êëèêîëåâîé ËÈÒÅÐÀÒÓÐÀ 1. Agrawal C.M., Athanasiou K.A., Heckman J.D. Biodegradable PLA/PGA polymers for tissue engineering in orthopaedica. Material Science Forum 1997; 250: 115-28. 2. Alcock H.R. Inorganic-organic polymers as route to biodegradable materials. Macromol. Symp. 1999; 144: 33-46. 3. Andriano K.P., Tabata Y., Ikada Y., Heller J. In vitro and In vivo comparison of bulk and surface hydrolysis in absorbable polymer scaffolds for tissue engineering. J. Biomed. Mater. Res. 1999; 48: 602-12. 4. Attawia M.A., Uhrich K.E., Botchwey E. et al. Cytotoxocity testing of poly(anhydride) for orthopaedic applications. J. Biomed. Mater. Res. 1995; 29: 1233-40. 5. Behravesh E., Yasko A.W., Engle P.S., Mikos A.G. Synthetic biodegradable polymers for orthopaedic applications. Clin. Orthop. 1999; 367S: 118-85. 6. Bostman O.M. Osteolytic changes accompanying degradation of absorbable fracture fixation implants. J. Bone Joint Surg. 1991; 73B: 679-82. 7. Bostman O.M. Intense granulomatous inflammatory lesions associated with absorbale internal fixation devices made of polyglycolide in ankle fractures. Clin. Orthop. 1992; 278: 178-99. 8. Bostman O., Paivaarinta U., Partio E. et al. Degradation and tissue replacement of an absorbable polyglycolide screw in the fixation of rabbit osteomies. J. Bone Joint Surg. 1992; 74A: 1021-31. 9. Bostman O., Partio E., Hirvensalo E., Rokannen P. Foreign-body reactions to polyglycolide screws. Acta Orthop. Scand. 1992; 63: 173-6. 10. Burg K.J.L., Porter S., Kellam J.F. Biomaterials development for bone tissue engineering. Biomaterials 2000; 21: 2347-59. 11. Chu C.C. The in vitro degradation of poly(glycolic acid) sutures- effect of pH. J. Biomed. Mater. Res. 1981; 15: 795-804. 12. Domb A.J. Poly(propylene glycol fumarate) compositions for biomedical applications. United States Patent 1989; 4888; 413: 1-31. 13. Domb A.J., Langer R. Polyanhydrides I: Preparation of high molecular weight polyanhydrides. J. Polym. Sci., Part A, Polymer Chem. 1987; 25: 3373-86. 14. Frazier D.D., Lathi V.K., Gerhart T.N., Hayes W.C. Ex vivo degradation of a poly(propylene glycol-fumarate) biodegradable particulate composite bone cement. J. Biomed. Mater. Res. 1997; 5; 35(3):383-9. 15. Gogolewski S., Pennings A.J. An artificial skin based on biodegradable 45 êèñëîò. Êðîìå òîãî, äàííûå ìàòåðèàëû îäîáðåíû FDA êàê áåçîïàñíûå ìàòåðèàëû äëÿ òêàíåèíæåíåðíûõ êîíñòðóêöèé. Îäíàêî èõ íåäîñòàòêè, òàêèå, êàê ïîâûøåíèå pH îêðóæàþùèõ òêàíåé ïðè ãèäðîëèçå, íåäîñòàòî÷íàÿ ìåõàíè÷åñêàÿ ïðî÷íîñòü, îãðàíè÷èâàþò èñïîëüçîâàíèå è íå ïîçâîëÿþò èõ ïðèìåíÿòü êàê óíèâåðñàëüíûé ìàòåðèàë äëÿ ìàòðèö è ïîäëîæåê. Íåñìîòðÿ íà íåêîòîðûå ìèíóñû, åùå â òå÷åíèå äëèòåëüíîãî âðåìåíè îíè ñìîãóò ñîñòàâèòü çíà÷èòåëüíóþ êîíêóðåíöèþ äðóãèì ïîëèìåðàì. Ê ñåãîäíÿøíåìó äíþ ìàòðèöû íà îñíîâå PGA, PLA è PGLA (PGDLA) ëåãëè â îñíîâó ñîçäàíèÿ òàêèõ îðãàíîâ è òêàíåé, êàê êîæà, êîñòü, õðÿù, ñóõîæèëèå, ïîïåðå÷íî-ïîëîñàòàÿ, ãëàäêàÿ è ñåðäå÷íàÿ ìûøöà, òîíêàÿ êèøêà è äð. è ïðîäîëæàþò ñâîå òðèóìôàëüíîå øåñòâèå ïî ïðîñòîðàì ðåãåíåðàòèâíîé ìåäèöèíû. Äðóãèå æå ïðåäñòàâèòåëè ñåìåéñòâà ïîëèýñòåðîâ çàéìóò, ïî-âèäèìîìó, ñâîå ìåñòî â ñòðóêòóðå áèîìàòðèö. mixtures of polylactides and polyurethanes for full-thickness skin wound covering. Makromol. Chem. Rapid. Commun. 1983; 4: 675-80. 16. Jen A.C., Peter S.J., Mikos A.G. Preparation and use of porous poly(ahydroxyester scaffolds for bone tissue engineering. In: Tissue Engineering Methods and Protocols. Morhgan J.R, Yarmush M.L eds Humana Press, Totowa: 1999; 133-40. 17. Kronenthal R.L. Biodegradable polymers in medicine and surgery. Polymer Sci. Technol. 1975; 8: 119-37. 18. Laurencin C.T., El-Amin S.F., Ibim S.E. et al. A highly porous 3-dimentional polyphophazene polymer matrix for skeletal tissue regeneration. J. Biomed. Mater. Res. 1996; 30: 133-8. 19. Peter S.J., Miller M.J., Yaszemski M.J., Mikos A.G. Poly(propylene fumarate). In: Handbook of Biodegradable Polymers. Domb A.J., Kost J., Wiseman D.M. eds. Harwood Academic Publishers, Amsterdam: 1997; 87-98. 20. Skarja G.A., Woodhouse K.A. Synthesis and characterization of degradable polyurethane elastomers containing an amino acid-based chain extender. J. Biomater. Sci. Polym. Ed 1998; 9: 271-95. 21. Temenoff J.S., Mikos A.G. Injectable biodegradable materials for orthopedic tissue engineering. Biomaterials 2000; 21: 2405-12. 22. Thomson R.C., Wake M.C., Yaszemski, Mikos A.G. Biodegradable polymer scaffolds to regenerate organs. Adv. Polymer. Sci. 1995; 122: 245-74. 23. Van Sliedregt A., van Blitterswijk C.A., Hesseling S.C. et al. The effect of the molecular weight of polylactic acid on in vivo biocompatibility. Adv. Biomaterials 1990; 9: 207-12. 24. VanSliedregt A., Radder A.M., deGroot K., Van Blitterswijk C.A. In vitro biocompatibility testing of polylactides Part I: Proliferation of different cell types. J. Mater. Sci.: Mater. Med. 1992; 3: 365-70. 25. William D.F., Mort E. Enzyme-accelerated hydrolysis of polyglycolic acid. J. Bioeng. 1977; 1: 231-8. 26. Wong W.H., Mooney D.J. Synthesis and properties of biodegradable polymers used as synthetic matrices for tissue engineering. In: Synthetic Biodegradable Polymer Scaffolds. Atala A., Mooney D., eds. Burkhauser, Boston; 1997: 51-84. 27. Yazemski M.J., Payne R.G., Hayes W.C. et al. Evolution of bone transplantation: molecular, cellular and tissue strategies to engineer human bone. Biomaterials 1996; 17: 175-85. 28. Gunatillake P.A., Adhikari R. Biodegradable synthetic polymer for tissue engineering. European Cells and Materials 2003; 5: 1-16. Êëåòî÷íàÿ òðàíñïëàíòîëîãèÿ è òêàíåâàÿ èíæåíåðèÿ ¹ 2, 2005