Linear Biodegradable Elastomers Based On Pendent Cyclic Ketals Substituted Poly (Epsilon-Caprolactone) For Soft Tissue Engineering

Biomaterials play a critical role in engineering of tissue constructs,working as an artificial extracellular matrix to support regeneration.As the elastic stretchability is a major mechanical property of the nature tissue,and the elastomeric characteristics have been described as important criteria for cell interaction by modulating cellular behavior,an increasing number of experts were devoted to develop biodegradable elastic scaffold with high flexibility and elasticity capability,which can be used to provide mechanical stimuli for tissue engineering constructs and match the mechanical properties of the soft tissue.Indeed,for the repair of most soft tissue types,one of the major problems encountered by biomaterials scientists has been difficulty in providing elastic mechanical support during the regeneration of the soft tissue constructs.To develop biomaterials with mechanical compliance for the soft tissue engineering,pendent cyclic ketals were introduced into polycaprolactone(PCL)by the ring-opening copolymerization of ?-caprolactone(CL)and 1,4,8-trioxaspiro-[4,6]-9-undecanone(TOSUO)using Sn(Oct)2 as catalyst.The obtained poly(CL-co-TOSUO)(PCT)can be considered as pendent cyclic ketals substituted PCL,the pendent cyclic ketals substitution decreased the crystallinity of the PCL and could be used to modify the elasticity of the PCL.At first,a series of PCT with different composition were synthesized according to the corresponding feed mass ratios,in which CL:TOSUO mass ratio equal to 10:0,9:1,8:2 and 7:3 respectively,the obtained copolymer were abbreviated as PCL,PCT 9-1,PCT 8-2 and PCT 7-3.The structures and the properties of the copolyester were characterized by 1H NMR,GPC,DSC,XRD,static contact angle,tensile test and cytotoxicity test.Compositional analyses indicate that TOSUO was randomly distributed in the PCT molecular chain.When the TOSUO content in the copolymers increased,the polymer crystallinity decreased progressively and the hydrophilicity increased accordingly.Tensile test indicated that the modulus and the tensile-strength of the copolyester decreased with the increased TOSUO content,but the elongation at break were firstly increased with increased TOSUO content and then decreased in the case of the amorphous PCT 7-3.The elongation at break of PCL,PCT 9-1,PCT 8-2 and PCT 7-3 were 366.85 ± 165.93%,902.76 ± 362.85%? 1463.33 ± 509.36 % and 251.81 ± 60.80%,respectively.From the mechanical properties of the copolyester,the PCT 8-2 might be the most suitable elastic copolyester for the soft tissue engineering.Then a series of PCT 8-2 with different molecule weight was synthesized by controlling the feed ratio of the initiator to the monomer,PCT 8-2 with number average molecular weight of 50 kDa,100kDa,200 kDa and 400 kDa were obtained,which were abbreviated as PCT 8-2 50 kDa,PCT 8-2 100 kDa,PCT 8-2 200 kDa and PCT 8-2 400 kDa.The obtained copolyester were characterized by 1H NMR,GPC,static contact angle and tensile test,the results shown that when the molecular weight the copolyester increased,the strength of the copolyester increased and the hydrophobicity of the copolyester decreased accordingly.As the scaffold of the tissue engineering,the cytocompatibility of the PCT was evaluated by the CCK-8 test using 3T3 cell.As the result of the static contact angle test,when the TOSUO content in the copolymers increased,the hydrophilicity of the copolyester increased accordingly.The CCK-8 results indicated that the cytocompatibility increased with the increased TOSUO content,the existence of the pendent cyclic ketals substitution promoted the cytocompatibility of the PCL.The tissue engineering scaffold should provide sufficient mechanical support during the tissue constructs;in vitro degradation results indicated that the pendent cyclic ketals substitution accelerated the degradation of the PCL.As the existence of the pendent cyclic ketals substitution decreased the crystallinity of the PCL and increased the hydrophilicity of the PCL,the degradation rate increased with the increased pendent cyclic ketals content.The pendent cyclic ketals substituted PCL could overcome the disadvantages of the too slow degradation of PCL.In conclusion,the introduction of the pendent cyclic ketals to the PCL chain can be used to produce high elastic biodegradable copolyester PCT.The mechanical properties of the elastic PCT could be tuned by altering the feed ratio of the monomer and the initiator,which could be used to satisfy the different elastic requirement of the soft tissue regeneration.Compared with the PCL,the elastic PCT showed higher cytocompatibility and faster degradation rate and should help meet the mechanical compliance requirements of soft tissue engineering application.