Composite bioabsorbable vascular stents via 3D bio-printing and electrospinning for treating stenotic vessels

A new type of vascular stent is designed for treating stenotic vessels. Aiming at overcoming the shortcomings of existing equipment and technology for preparing a bioabsorbable vascular stent （BVS）, a new method which combines 3D bio-printing and electrospinning to prepare the composite bioabsorbable vascular stent （CBVS） is proposed. The inner layer of the CBVS can be obtained through 3D bio- printing using poly-p-dioxanone （PPDO）. The thin nanofiber film that serves as the outer layer can be built through electrospinning using mixtures of chitosan-PVA （poly （vinyl alcohol））. Tests of mechanical properties show that the stent prepared through 3D bio-printing combined with electrospinning is better than that prepared through 3D bio- printing alone. Cells cultivated on the CBVS adhere and proliferate better due to the natural, biological chitosan in the outer layer. The proposed complex process and method can provide a good basis for preparing a controllable drug-carrying vascular stent. Overall, the CBVS can be a good candidate for treating stenotic vessels.

Bioabsorbable Barrier Membrane Combined with rhBMP-2 Improved Bone Formation in an Experimental Model of Compromised Healing But Was Not Superior to rhBMP-2 Alone

Objective: Bioabsorbable barrier membranes placed over alveolar ridge bone defects are routinely used in dental surgery to promote bone formation. Combining these osteoconductive membranes with osteoinductive Bone Morphogenetic Proteins could prove useful in long bone fracture treatment. The hypothesis was tested in a clinically relevant model of compromised healing. Methods: Four groups of 8 rabbits underwent unilateral mid-tibial osteotomy, excision of periosteum and endosteum, and plate fixation. One group had rhBMP-2 deposited between the bone ends and Membrane wrapped around the osteotomy, the second group had Membrane wrapped around the osteotomy, the third group had rhBMP-2 placed between the bone ends, and the fourth group received no additional treatment. Results: After 7 weeks, callus size and blood flow were significantly higher in the Membrane+rhBMP-2 group than in the rhBMP-2 treated group, but torsion to failure test showed no significant difference. Membrane treatment and no treatment led to non-union. Conclusion: Absorbable barrier membrane combined with rhBMP-2 enhances bone formation, but has no advantage to rhBMP-2 alone. Membrane alone wrapped around the osteotomy was unable to prevent non-union formation.

Study on In-Vitro Degradation of Bioabsorbable Polymers Poly(hydroxybutyrate-co-valerate)-(PHBV)and Poly(caprolactone)-(PCL)

The increasing use of bioabsorbable polymeric materials in medicine has stimulated researchers in the materials field to search for solutions for the replacement of metallic artifacts by bioabsorbable polymers. Therefore, this study describes the in vitro degradation of PHBV, PCL and the blends of these polymers, both of which are bioabsorbable polymers. The samples were prepared by extrusion followed by injection, and subjected submitted to in vitro degradation in phosphate buffered saline solution with pH 7.3 and kept at 37° C. Through the characterization of the variation of mass, molar mass, mechanical properties and morphology, the results indicated that the samples analyzed are more stable to hydrolytic degradation when compared to other bioabsorbable polymers. The materials indicate signs of degradation after 30 days, with a small reduction in the molar mass. After 180 days, the materials indicated a significant reduction of molar mass and reduction in the mechanical properties.

Long-term clinical outcomes after bioabsorbable polymer- and durable polymer-based sirolimus-eluting stents implantation： two-year follow-up results from a large single-center database

Background Several clinical trials have shown that sirolimus-eluting stents significantly reduce the risk of restenosis after percutaneous coronary intervention （PCI）. The FIREBIRD stent （coated with durable polymer） and the EXCEL stent （coated with bioabsorbable polymer） are two different types of sirolimus-eluting stents made in China; both have been approved for clinical use in China by the State Food and Drug Administration. The mid-term （6-month） angiographic and clinical results of both stents have been confirmed exciting perspective outcomes. However, it is unclear whether there are differences in the long-term safety and efficacy between the two types of stents in daily practice.Methods All consecutive patients undergoing elective PCI with EXCEL or FIREBIRD stents between June 1,2006 and December 31, 2006 at Fu Wai Hospital in Beijing were included. Patients were classified from the index admission according to stent types （EXCEL or FIREBIRD） used. Clinical and procedural risk factors were collected prospectively. With propensity score matching without replacement, the frequency of major adverse cardiac events （MACE, a composite of death, myocardial infarction or target vessel revascularization） and stent thrombosis during a 2-year follow-up period were compared between the two groups.Results A total of 474 patients were treated with EXCEL, and 640 were treated with FIREBIRD. Three hundred and ninety-seven EXCEL patients were matched to 397 FIREBIRD patients, 2-year risk-adjusted MACE rates were 6.1% in EXCEL group and 7.6% in FIREBIRD group （HR 0.84, 95%CI0.50-1.43）, whereas the respective rates for mortality, myocardial infarction and target-vessel revascularization were 2.3% vs 2.8% （HR 0.74, 95%CI0.30-0.85）, 1.8% vs 1.3% （HR 1.41,95%CI 0.45-4.43） and 2.5% vs 4.0% （HR 0.62, 95%CI0.28-0.37）, respectively. Cumulative incidence of stent thrombosis at 2 years was 1.8% in the EXCEL group vs 1.3% in the FIREBIRD group （P=0.5610）, whereas the rate of very late stent thrombosis was 0.5% vs 1.3% （P=0.2550）.Conclusions Results from this long-term, relatively large size, single-center study showed that both of the EXCEL and the FIREBIRD sirolimus-eluting stent had similar and lower incidence of MACE after PCI in daily practice.

A comparison of clinical and angiographic outcomes after Excel bioabsorbable polymer versus Firebird durable polymer rapamycin-eluting stent for the treatment of coronary artery disease in a “real world” setting:six-month follow-up results

Background Several clinical trials have shown that rapamycin-eluting stents significantly reduce the risk of restenosis after percutaneous coronary intervention （PCI）. The Firebird stent and the Excel stent （coated with bioabsorbable polymer） are two different types of rapamycin-eluUng stents made in China, both have been recently approved for clinical use in China by State Food and Drug Administration. However, it is unclear whether there are differences in safety and efficacy between the two types of stents in daily practice. Methods In the month of June 2006, a total of 190 consecutive patients were treated exclusively with Firebird stents （n=93, Firebird group） or Excel stents （n=97, Excel group） in our center and were included in this study. The frequency of major adverse cardiac events （MACE, a composite of death, myocardial infarction or target lesion revascularization）, binary restenosis, and late lumen loss and stent thrombosis dudng a six-month follow-up period were compared between the two groups. Results Patient and lesion characteristics were comparable between the groups. Major adverse cardiac event rates were low in hospital and at 6 months （2.1% in the Excel group and 0% in the Firebird group, P〉 0.05）. The 6-month angiographic in-stent restenosis rate was 0% in both groups, with an associated late loss of （0.15 ± 0.21） mm versus （0.14 ± 0.20） mm （P=0.858） and the in-segment restenosis rate was also 0% for the Excel group and the Firebird group. There was no definite stent thrombosis identified in either group during the six-month follow-up period and only one patient in the Excel group had probable stent thrombosis in hospital. Conclusions Results from this mid-term, single-center study showed that both of the Firebird and the Excel rapamycin eluUng stent had similar effects on reducing the incidence of MACE and the risk of restenosis （both in-stent and in-segment binary restenosis） after PCI in daily practice.

Safety and efficacy of cobalt chromium alloy based sirolimus-eluting stent with bioabsorbable polymer in porcine model

Background First generation drug-eluting stents （DESs） were based on 316L stainless steel and coated with a permanent polymer. The vessel wall of these DESs was inflammatory and late in-stent thrombosis was reported. Hence, cobalt chromium based DES coated with a bioabsorbable polymer was an alternate choice. Methods Cobalt chromium based DES with bioabsorbable polymer （Simrex stent） as well as control stents （Polymer stent and EXCELTM stent） were implanted into porcine arteries. At a designated time, angiography, quantitative coronary angiography （QCA） analysis, histomorphometry, and electron-microscopical follow-up were performed. Results A total of 98 stents of all the three groups were harvested. At week 24, percent diameter stenosis （%DS）, late loss （LL）, and percent area stenosis （%AS） of Simrex was （12.9±0.4）%, （0.35±0.02） mm, and （24.5±4.2）%, respectively, without significant difference in comparison to commercialized EXCELTM stent. Slight inflammatory reaction was seen around the stent strut of Simrex, just as in the other two groups. Electron-microscopical follow-up suggested that it might take 4-12 weeks for Simrex to complete its re-endothelialization process. Conclusions Cobalt chromium based, bioabsorbable polymer coated sirolimus-eluting stent showed excellent biocompatibility. During 24 weeks observation in porcine model, it was proved that this novel DES system successfully inhibited neointima hyperplasia and decreased in-stent stenosis. It is feasible to launch a clinical evaluation to improve the current prognosis of DES implantation.

A STUDY OF STRUCTURE AND PROPERTY CHANGES OF BIODEGRADABLE POLYGLYCOLIDE AND POLY(GLYCOLIDE-co-LACTIDE)FIBERS DURING PROCESSING AND IN VITRO DEGRADATION

Structure and properties of bioabsorbable polyglycolide (PGA) and poly(glycolide-co-lactide) (PGA-co-PLA)fibers were investigated during several industrial processing stages and in vitro degradation by means of wide-angle X-raydiffraction (WAXD), dynamic mechanical analysis (DMA) and mechanical property tests. In the orientation stage, the PGAfibers were found to have higher degrees of crystallinity than corresponding PGA-co-PLA samples produced under similarconditions. In the hot-stretching and post-annealing stages, after fibers were braided, PGA samples were found to gain morecrystallinity and higher T_g than PGA-co-PLA samples. The higher crystallinity in PGA fibers resulted in a slower rate ofdegradation. DMA results showed that a great deal of internal stress that was built during orientation and hot-stretchingstages was released in the post-annealing stage for a1l PGA and PGA-co-PLA samples. During earlier stages of in vitrodegradation, both PGA and PGA-co-PLA samples exhibited the typical cleavage-induced crystallization mechanism. Theheat shrinkage in the glass transition area was found to disappear after 6-8 days of degradation for all PGA and PGA-co-PLAsamples, indicating the amorphous portions of the polymers lost orientation after a short period in the buffer solution, mostlikely due to relaxation of the cleaved chains.

Radial Compressive Property of Nerve Regeneration Conduit with PGLA Biodegradable Fibers

Radial compressive property greatly influences nerve regeneration and functional recovery. In this study,four types of braided bioabsorbable nerve regeneration conduits made from poly(glycolide-co-L-lactide)(PGLA) were produced. The aim is to test the radial compressive force and elastic recovery ratio of nerve regeneration conduits. The results indicated that radial compressive force was closely related to the inner diameter and length of tubes and elastic recovery ratio was nearly unaffected by these two factors.

THE SYNTHESIS AND CHARACTERIZATION OFPOLY-L-LACTIDE USED FOR THE INTERNALFIXATION OF BONE FRACTURE

A high Mw of PLLA was synthesized, it intended to be used in the manufacture ofbioabsorbable screw applied in bone fracture internal fixation. The optical reactionconditions have been discussed.

Pitfalls and promises of bile duct alternatives:A narrative review

Biliodigestive anastomosis between the extrahepatic bile duct and the intestine for bile duct disease is a gastrointestinal reconstruction that abolishes duodenal papilla function and frequently causes retrograde cholangitis.This chronic inflammation can cause liver dysfunction,liver abscess,and even bile duct cancer.Although research has been conducted for over 100 years to directly repair bile duct defects with alternatives,no bile duct substitute(BDS)has been developed.This narrative review confirms our understanding of why bile duct alternatives have not been developed and explains the clinical applicability of BDSs in the near future.We searched the PubMed electronic database to identify studies conducted to develop BDSs until December 2021 and identified studies in English.Two independent reviewers reviewed studies on large animals with 8 or more cases.Four types of BDSs prevail:Autologous tissue,non-bioabsorbable material,bioabsorbable material,and others(decellularized tissue,3D-printed structures,etc.).In most studies,BDSs failed due to obstruction of the lumen or stenosis of the anastomosis with the native bile duct.BDS has not been developed primarily because control of bile duct wound healing and regeneration has not been elucidated.A BDS expected to be clinically applied in the near future incorporates a bioabsorbable material that allows for regeneration of the bile duct outside the BDS.

Effect of Absorbable Hydroxyapatite/Poly-DL-Lactide Rods on Experimental Fracture Healing

Summary: In order to investigate the effect of a new institute-designed absorbable hydroxyapatite microparticles/poly-DL-lactide (HA/PDLLA) fracture fixation devices on experimental fracture healing, 25 rabbits with a transverse transcondylar osteotomy of the distal femur were fixed in- tramedullary by a HA/PDLLA rod (4. 5 mm in diameter, 30-40 mm in length). The follow-up time lasted 1, 2, 4, 6 and 12 week(s). Roentgenographic, histological and ultrastructural analyses were conducted. The results showed that all osteotomies united within 6 weeks without delay. No accumulation of inflammatory cells was seen. Ultrastructural studies showed that polymorphonuclear neutrophils and macrophages were observed mainly at the 1st week, but only few were noted at the 2nd week. The inflammatory and debridement stages were not prolonged. Large amount of active fibroblasts and some chondroblasts were observed at the 2nd week, suggesting a fibrous callus stage. The main cellularity at 4th week was osteoblasts and osteocytes. Part of osteocytes had already entered the static stage at the 6th week. Our experiment showed that the HA/PDLLA had good biocompatibility, sufficient mechanical strength and caused no delay to the fracture healing.

Biodegradable stent

The bare metal stent (BMS) used in the blood vessel caused the restenosis after the operation due to formation and proliferation of neointimal. Recently, as a method to overcome the problems of BMS, drug eluting stent (DES) is developed and being applied to human body which has drug reducing restenosis applied on the metal surface. DES has the advantage of greatly reducing the restenosis after the operation;however, metal stent remains in the body after the drug is released causing issues such as late thrombosis and restenosis so that currently the attention is increasing for biodegradable materials that reduce restenosis and thrombosis by degrading as a certain amount of time passes after the drug is released by the stent material. In this review, the study trend of biodegradable stent will be explained.

Antibiotic-Loaded Resorbable Bone-Graft Substitute： A New Treatment for Osteomyelitis/Osteitis

Patients with osteomyelitis require lengthy antibiotic treatment, often only to see the inflammation flare up once antibiotics are suspended. Unfortunately, patients often discontinue the antibiotic treatment due to collateral effects. Patients with osteitis are often polymorbid patients with other severe diseases such as diabetes mellitus and polyneuropathy, arteriopathy or polyarthfitis with immunosuppression. The eight patients included in the study presented nine bones with osteomyelitis （macroscopically, bacteriologically, histologically or radiologically）. The diseased part of the bone was resected, a locally radical debridement was done and a biopsy for bacteriology and histology were taken. The residual bone was then drilled out and filled with antibiotic-loaded （gentamicin） resorbable bone-graft substitute under radiologic imaging control. In total, seven patients are currently without recurrent osteomyelitis with a mean follow-up of 5.77 months （2-11 months）. The Kaplan Meier curve shows 80% survival rate without recurrent osteomyelitis at 11 months. Only one patient suffering from Morbus Buerger had a relapse osteomyelitis after cutting off severing his foot while swimming in the sea. Antibiotic-loaded resorbable bone-graft substitute is easy to use, has in our hands few complications and low recurrence rate.

Microalgae as Bioabsorbents for Treating Mixture of Electroplating and Sewage Effluent

The effectiveness of copper and nickel uptake by microalgae grown in the mixture of electroplating effluent and sewage was studied. The results showed that a high percentage of copper removal (68.1%-88.2%) was achieved by Chlorellapyrenoidosa (strain No. 26) reared in the mixture of 90% electroplating effluent and 10% raw sewage during the first 3 days despite the fact that cell growth was inhibited. Similar results were also obtained by using Chlorella HKBC-C3, another species collected from one of the heavy metal polluted sites in Hong Kong, isolated and cultured in the Biology Department. There was no significant difference (P>0.05) in the removal of copper and nickel from the effluent between these 2 algal species. However, it was noted that removal of nickel from the mixture by the two species were comparatively lower (<20%) than the removal of copper (>68%).

Effects of serum proteins on corrosion rates and product bioabsorbability of biodegradable metals

Corrodible metals are the newest kind of biodegradable materials and raise a new problem of the corrosion products.However,the removal of the precipitated products has been unclear and even largely ignored in publications.Herein,we find that albumin,an abundant macromolecule in serum,enhances the solubility of corrosion products of iron in blood mimetic Hank’s solution significantly.This is universal for other main biodegradable metals such as magnesium,zinc and polyester-coated iron.Albumin also influences corrosion rates in diverse trends in Hank’s solution and normal saline.Based on quantitative study theoretically and experimentally,both the effects on corrosion rates and soluble fractions are interpreted by a unified mechanism,and the key factor leading to different corrosion behaviors in corrosion media is the interference of albumin to the Ca/P passivation layer on the metal surface.This work has illustrated that the interactions between metals and media macromolecules should be taken into consideration in the design of the next-generation metal-based biodegradable medical devices in the formulism of precision medicine.The improved Hank’s solution in the presence of albumin and with a higher content of initial calcium salt is suggested to access biodegradable metals potentially for cardiovascular medical devices,where the content of calcium salt is calculated after consideration of chelating of calcium ions by albumin,resulting in the physiological concentration of free calcium ions.

新型完全生物可吸收封堵器经导管封堵膜周部室间隔缺损:一项多中心前瞻性随机对照研究

生物可吸收封堵器的应用有望降低传统金属封堵器并发症的风险.之前研制的生物可吸收封堵器存在不完全降解的局限性并导致新的并发症,因此目前尚未有相关产品获批上市.本研究使用了一种新型完全可吸收封堵器,旨在探索完全可吸收封堵器治疗室间隔缺损的疗效和安全性.从2019年4月到2020年1月,本研究在七个医学中心入组125名膜周部室间隔缺损患者,经筛查后108名患者被纳入研究并随机分为植入生物可吸收封堵器实验组和金属封堵器组.所有受试者均成功植入封堵器并完成24个月的随访.生物可吸收封堵器组患者经胸超声心动图显示高亮回声在24个月内逐渐消失,说明可吸收封堵器在体内实现完全降解.对比金属封堵器,实验组器械相关心律失常发生率(5.56%vs.14.81%,P=0.112)和持续传导阻滞发生率(0/54 vs.6/54,P=0.036)显著降低.本研究提示新型完全可吸收封堵器可以在单纯超声引导下实现成功植入,同时降低术后永久性心律失常的发生率.

Mg-based absorbable membrane for guided bone regeneration(GBR): a pilot study

A novel calcium-phosphate(Ca–P)-coated magnesium(Mg) membrane used for guided bone regeneration(GBR) was studied.The microstructural characterization, electrochemical test, immersion test,fluorescence labeling analysis and histopathological evaluation were carried out.The results showed that Ca–P coating could obviously improve the corrosion resistance of the pure Mg membrane.The in vivo results showed that Mg membrane coated with Ca–P would take 8 weeks to be completely absorbed.However, Mg membrane was completely absorbed within 1 week.Histopathological evaluation showed that the Ca–P-coated Mg membranes were significantly better than Ti membranes at the early implantation time(4 weeks), and with the time prolonging,the performance of the coated Mg membrane was not as good as pure Ti membranes(but still better than blank group) at 8 and 12 weeks.The coated biodegradable Mg membrane had a good promising application in GBR.But further studies have to be done to further decrease the degradation rate of pure Mg membrane.