Biomaterial and tissue-engineering strategies for the treatment of brain neurodegeneration

The incidence of neurodegenerative diseases is increasing due to changing age demographics and the incidence of sports-related traumatic brain injury is tending to increase over time.Currently approved medicines for neurodegenerative diseases only temporarily reduce the symptoms but cannot cure or delay disease progression.Cell transplantation strategies offer an alternative approach to facilitating central nervous system repair,but efficacy is limited by low in vivo survival rates of cells that are injected in suspension.Transplanting cells that are attached to or encapsulated within a suitable biomaterial construct has the advantage of enhancing cell survival in vivo.A variety of biomaterials have been used to make constructs in different types that included nanoparticles,nanotubes,microspheres,microscale fibrous scaffolds,as well as scaffolds made of gels and in the form of micro-columns.Among these,Tween 80-methoxy poly(ethylene glycol)-poly(lactic-co-glycolic acid)nanoparticles loaded with rhynchophylline had higher transport across a blood-brain barrier model and decreased cell death in an in vitro model of Alzheimer’s disease than rhynchophylline or untreated nanoparticles with rhynchophylline.In an in vitro model of Parkinson’s disease,trans-activating transcriptor bioconjugated with zwitterionic polymer poly(2-methacryoyloxyethyl phosphorylcholine)and protein-based nanoparticles loaded with non-Fe hemin had a similar protective ability as free non-Fe hemin.A positive effect on neuron survival in several in vivo models of Parkinson’s disease was associated with the use of biomaterial constructs such as trans-activating transcriptor bioconjugated with zwitterionic polymer poly(2-methacryoyloxyethyl phosphorylcholine)and protein-based nanoparticles loaded with non-Fe hemin,carbon nanotubes with olfactory bulb stem cells,poly(lactic-co-glycolic acid)microspheres with attached DI-MIAMI cells,ventral midbrain neurons mixed with short fibers of poly-(L-lactic acid)scaffolds and reacted with xyloglucan with/without glial-derived neurotrophic factor,ventral midbrain neurons mixed with Fmoc-DIKVAV hydrogel with/without glial-derived neurotrophic factor.Further studies with in vivo models of Alzheimer’s disease and Parkinson’s disease are warranted especially using transplantation of cells in agarose micro-columns with an inner lumen filled with an appropriate extracellular matrix material.

Next-generation surgicalmeshes for drug delivery and tissue engineering applications:materials,design and emerging manufacturing technologies

Surgical meshes have been employed in the management of a variety of pathological conditions including hernia,pelvic floor dysfunctions,periodontal guided bone regeneration,wound healing and more recently for breast plastic surgery after mastectomy.These common pathologies affect a wide portion of the worldwide population;therefore,an effective and enhanced treatment is crucial to ameliorate patients’living conditions both from medical and aesthetic points of view.At present,non-absorbable synthetic polymers are the most widely used class of biomaterials for the manufacturing of mesh implants for hernia,pelvic floor dysfunctions and guided bone regeneration,with polypropylene and poly tetrafluoroethylene being the most common.Biological prostheses,such as surgical grafts,have been employed mainly for breast plastic surgery and wound healing applications.Despite the advantages of mesh implants to the treatment of these conditions,there are still many drawbacks,mainly related to the arising of a huge number of post-operative complications,among which infections are the most common.Developing a mesh that could appropriately integrate with the native tissue,promote its healing and constructive remodelling,is the key aim of ongoing research in the area of surgical mesh implants.To this end,the adoption of new biomaterials including absorbable and natural polymers,the use of drugs and advanced manufacturing technologies,such as 3D printing and electrospinning,are under investigation to address the previously mentioned challenges and improve the outcomes of future clinical practice.The aim of this work is to review the key advantages and disadvantages related to the use of surgical meshes,the main issues characterizing each clinical procedure and the future directions in terms of both novel manufacturing technologies and latest regulatory considerations.

赝复体钛网同期植入修复上颌骨切除后眶面部缺损

背景:上颌骨创伤或肿瘤切除后可发生面部骨缺损,严重影响患者的外观和生活质量,早期修复对患者意义重大。目的:探讨上颌骨切除后同期钛网与赝复体植入修复眶面部缺损以及长期疗效。方法:选取2009年6月至2013年1月在解放军第四军医大学西京医院耳鼻咽喉头颈外科接受上颌骨切除的患者,治疗中同期植入钛网修复眶底以及上颌窦前壁骨质缺损的上颌窦恶性肿瘤患者共21例,其中上颌骨部分切除4例,上颌骨全切11例,上颌骨扩大切除6例,随访观察钛网在上颌骨切除后遗留的面中部及眶区缺损的修复效果。结果与结论:所有患者同期钛网植入后创口均一期愈合,颜面部轮廓对称,眼球功能正常,患者对颜面部外观基本满意,联合赝复体后能进软食,语言清晰,2例患者在修复后辅助放疗,出现钛网植入体部分外露,经临近皮瓣转移修复后痊愈。结果显示,钛网可以对上颌骨缺损患者进行面部修复重建,对恢复面部形态、防止复视发生、后期功能修复以及提高患者生存质量均有明确疗效。

骨科修复重建中医用钛网的应用

背景:钛网在骨科修复重建治疗中效果良好,已得到广泛的应用。目的:探讨钛网在颅骨缺损、四肢骨缺损、大块胸壁缺损、掌指骨骨折及颌面部骨折等相关骨科疾病应用中的可靠性及优越性。方法:收集钛网在颌面骨缺损、大块胸壁缺损、颅骨缺损、四肢长骨干骨缺损、掌指骨折等骨科疾病修复重建的临床研究及相关实验研究,评价钛网治疗骨科疾病的效果。结果与结论:与其他修复材料相比,钛网在骨科修复重建中有明显的优越性,但作为重建材料尚有一定的缺点,如X射线透光性差等。因此,在骨科应用中应针对不同部位的缺损采用不同的操作方法,以减少并发症的发生和达到更好的修复重建效果。

聚醚醚酮和钛网材料修补颅骨缺损远期效果及不良事件的差异:前瞻性、单中心、非随机对照、2年随访临床试验方案

背景:聚醚醚酮和钛网材料是目前临床上用于颅骨修补的常用修复材料,但目前尚缺乏两种材料的远期(如术后2年)修复效果及安全性对比的临床试验证据。目的:评估聚醚醚酮和钛网材料在颅骨修补中的远期修复效果及不良事件的差异。方法:方案设计为前瞻性、单中心、非随机、对照、2年随访、临床试验。将纳入中国医科大学附属第四医院的颅骨修补住院患者60例,按术中颅骨修补材料的不同分为2组,试验组采用聚醚醚酮材料修复,对照组采用钛网材料修复,每组30例,术后随访6,12,24个月。试验已获得中国医科大学附属第四医院医学伦理委员会批准,伦理批件号:EC-2021-HS-002,批准时间:2021-02-01。此试验符合世界医学会制定的《赫尔辛基宣言》的要求;所有患者均需签署知情同意书。试验对象招募时间为2021-08-01/2022-08-01,结果分析时间为2024-09-01/2024-09-30,试验完成时间为2024-10-31。结果与结论:试验的主要结局指标为术后24个月采用修复体失败率评估修复效果;次要结局指标为术后6,12个月修复体失败率、术后6,12,24个月采用不良事件发生率评估植入材料的安全性,采用格拉斯哥预后量表评分评估神经功能恢复情况,采用塑形满意度评分评估颅骨塑形效果,采用头部CT成像评估颅骨损伤愈合情况,采用成本效果比和增量成本效果比评估两种材料的成本效果差异。该试验希望证实,与钛网材料修复相比,采用聚醚醚酮材料进行颅骨修复后的2年修复效果更好,不良事件发生率更低,生物相容性更好,在远期疗效及安全性方面优势明显。试验已在中国临床试验注册中心注册(注册号:ChiCTR2100043703),注册时间:2021-02-27,方案版本号1.0。

生物补片应用于先天性无阴道的疗效观察

目的 评价生物补片在治疗先天性无阴道的疗效。方法 选择我院2013年9月至2014年12月18例先天性无阴道患者行生物补片阴道成形术。结果 18例患者均获成功,随访3∽18个月,11例有性生活者术后性功能正常。结论 生物补片阴道成形术简便可行,安全有效。

两种阴道成形术治疗先天性无阴道的疗效探讨

目的探讨生物补片代阴道成形术与腹腔镜下回肠代阴道成形术治疗先天性无阴道的疗效。方法 2008年6月-2015年3月收治23例先天性无阴道患者。15例使用胸普外科修补膜行生物补片代阴道成形术,8例行腹腔镜下回肠代阴道成形术。结果生物补片代阴道成形术和腹腔镜回肠代阴道成形术手术时间分别为（59.3±7.0）、（136.3±20.0）min,术中出血量（20.7±5.9）、（22.5±4.6）ml,术后排气时间（1.9±0.5）（3.4±1.2）d,术后住院时间（5.5±0.5）、（7.2±1.0）d,住院费用（2.95±1.27）万、（2.49±0.08）万元。23例均无并发症。术后随访18-72个月,平均33.7月。8例生物补片代阴道成形术及5例腹腔镜回肠代阴道成形术患者对性生活较为满意,阴道湿润感较好,疼痛感较少;5例生物补片代阴道成形术及1例腹腔镜回肠代阴道成形术患者无性生活,自述佩戴模具时阴道内阻力小,无明显不适感。结论两种术式治疗先天性无阴道疗效确切,可满足患者性生活的需求。生物补片代阴道成形术的手术方法简单,耗时短,损伤小,术后恢复快,但费用较高。

3D打印数字化塑形聚醚醚酮和钛网颅骨修补后并发症异同和应用改进

背景:颅骨修补材料种类繁多,但目前仍然没有哪种材料能在生物相容性、性价比等各方面性能上全部满足临床需要。目的:分析3D打印数字化塑形聚醚醚酮和钛网修补颅骨缺损的术后并发症差异,针对并发症明确改进方向。方法:回顾性分析长江大学附属黄冈市中心医院2014年6月至2021年6月收治的207例颅骨缺损患者,男157例,女50例,年龄16-68岁,其中42例使用聚醚醚酮修补材料,165例使用钛网修补材料。术后第3周,进行额颞顶区缺损区塑形满意度调查;术后随访统计并发症发生情况。结果与结论:(1)聚醚醚酮组32例进行额颞顶区缺损修补,塑形满意度为56.3%;钛网组117例进行额颞顶区缺损修补,塑形满意度为75.2%,两组塑形满意度比较差异有显著性意义(P<0.05);(2)聚醚醚酮组42例中14例发生并发症,其中皮下积液12例(28.6%)、癫痫1例、额部螺钉固定处隆起疼痛1例,并发症发生率为33.3%;钛网组165例中28例发生并发症,其中皮下积液15例(9.1%)、癫痫7例、颅内感染2例、材料外露2例、颅内血肿1例、材料松动1例,并发症发生率为17.0%,两组间皮下积液及总并发症发生率比较差异有显著性意义(P<0.05);(3)结果表明,额颞顶区骨质缺损处采用钛网修补较聚醚醚酮材料修补美观、满意度更高,聚醚醚酮材料应用于颅骨修补的主要改进方向是降低术后皮下积液的发生率。

Evaluation of corneal cell growth on tissue engineering materials as artificial cornea scaffolds

The keratoprosthesis(KPro;artificial cornea)is a special refractive device to replace human cornea by using heterogeneous forming materials for the implantation into the damaged eyes in order to obtain a certain vision.The main problems of artificial cornea are the biocompatibility and stability of the tissue particularly in penetrating keratoplasty.The current studies of tissue-engineered scaffold materials through comprising composites of natural and synthetic biopolymers together have developed a new way to artificial cornea.Although a wide agreement that the long-term stability of these devices would be greatly improved by the presence of cornea cells,modification of keratoprosthesis to support cornea cells remains elusive.Most of the studies on corneal substrate materials and surface modification of composites have tried to improve the growth and biocompatibility of cornea cells which can not only reduce the stimulus of heterogeneous materials,but also more importantly continuous and stable cornea cells can prevent the destruction of collagenase.The necrosis of stroma and spontaneous extrusion of the device,allow for maintenance of a precorneal tear layer,and play the role of ensuring a good optical surface and resisting bacterial infection.As a result,improvement in corneal cells has been the main aim of several recent investigations;some effort has focused on biomaterial for its well biological properties such as promoting the growth of cornea cells.The purpose of this review is to summary the growth status of the corneal cells after the implantation of several artificial corneas.

生物补片法阴道成形术治疗先天性无阴道的疗效分析

目的：探讨采用生物补片法阴道成形术治疗先天性无阴道（Mayer-Rokitansky-K＆#252;ster-Hauser，MRKH）综合征的疗效。方法选取2006—2013年广东省佛山市妇幼保健院妇科住院收治的15例MRKH综合征患者作为研究对象，均采用生物材料[人工脱细胞真皮（acelluardermalmatrixallograft，ADM）]行人工阴道成形术，对其术中、术后及随访情况进行分析。结果15例患者手术均顺利完成，术中和术后均无严重不良反应发生，手术平均时间（69．4±13．6）min，术中平均出血量（50．6±15．3）ml，术后排气时间（57．7±13．2）h，术后平均住院时间（33．9±5．9）d，住院平均费用（15683．9±1111．8）元。结论生物补片法人工阴道成形术能够有效地治疗先天性无阴道综合征，手术方式理想、安全、有效，为患者重塑一个在解剖上、功能上接近正常的人工阴道，值得在临床上推广和应用。

Hernia Mesh and Hernia Repair:A Review

Hernia repair for primary and incisional hernia is the most commonly performed abdominal surgery done with extremely high costs.Treatment for hernia requires surgery to close the defect;however,there are post-operative complications like chronic pain,adhesion,and infection that are common.Hernia repair involves two types of biomaterials:a fixation biomaterial and a mesh biomaterial to close the defect.Synthetic meshes,mostly made from different polymers,provide adequate mechanical support but are associated with postoperative complications like infection.Biological meshes are derived from allografts and xenografts that are prone to less infection;however,their mechanical strength may be too weak depending the characteristics of the hernia defect.Novel meshes being developed try to combat the post-operative complications of current surgical meshes.Composite meshes that have two different surfaces have shown to have less adhesion effects but still produce varying inflammatory responses.Drug-loaded meshes are also a novel mesh that is designed to reduce infection with antibiotics.This review will highlight the different fixation methods as well as the pros and cons of different mesh options.Possible future improvements will be highlighted as well.

应用膨体聚四氟乙烯补片行乙状结肠造口腹膜内固定对造口旁疝的预防

目的 评估应用膨体聚四氟乙烯补片行乙状结肠造口腹膜内固定预防造口旁疝的结果。方法2003年1月至2005年1月间中山大学附属第一医院需行腹会阴联合切除直肠肿瘤（Miles术）手术的60例患者按信封法随机分成两组，每组30例。对照组行经腹膜经腹直肌乳头型造口，试验组加用膨体聚四氟乙烯补片行乙状结肠造口腹膜内固定．观察造口并发症及随访造口旁疝发生情况。结果对照组有8例（26．7％）出现造口旁疝；观察组患者无造口旁疝发生。结论使用膨体聚四氟乙烯补片行乙状结肠造口腹膜内固定可预防造口旁疝的发生。

盆底疝的发病特点及治疗现状

盆底疝(pelvic floor hernia)从解剖部位及疝内容物可以分为:坐骨孔疝(ischiatic hernia)、闭孔疝(obturator hernia)、会阴疝(perineal hernia)、盆底腹膜疝(peritoneo-cele)。主要表现为盆腔疼痛、下坠感、性功能障碍、尿失禁、排便不尽感,以及盆腔器官脱垂。临床上盆底疝主要采用传统张力性缝合修补和人工合成材料疝修补的手术方法,临床应用虽广泛,但有诸多不足。近年来,应用生物材料补片修复盆底疝已逐渐成为临床应用趋势和研究热点。

先天性无阴道综合征生物补片法阴道成形术的手术方法介绍和临床结局

目的先天性无阴道(Mayer-Rokitansky-Küster-Hauser)综合征手术治疗方法繁多,探讨及评价生物补片法阴道成形术的手术疗效及临床结局。方法选自2006～2011年北京协和医院应用生物材料[人工脱细胞真皮(acelluar dermal matrix allograft,ADM)]人工阴道成形术的MRKH综合征患者53例,进行术后随访,以及术后随诊超过6月的患者采用女性性功能指数(female sexual function index,FSFI)问卷来了解性生活情况。对照组选择同期健康体检、年龄因素匹配的患者进行FSFI问卷。结果采用Mann-Whitney U检验统计分析。结果 53例患者均没有出现膀胱或直肠损伤、盆腔血肿等并发症,术后随诊时间为(21.1±10.4)月。术后3月的解剖学成功率为100%。功能学评价方面,所有患者对自身体像满意。术后有性生活者32例进行FSFI问卷,MRKH患者FSFI总分为(26.7±3.9),在性欲、性唤起、湿润感、性高潮、性生活满意度、疼痛感这些方面的分值,与正常对照组比较均没有统计学差异[(24.6±9.3),P>0.05]。结论生物补片法人工阴道成形术手术简便易行,安全有效。

Current progress of skin tissue engineering:Seed cells, bioscaffolds, and construction strategies

The development of cell biology, molecular biology, and material science, has been propelling biomimic tissue-engineered skins to become more sophisticated in scientificity and more simplified in practicality. In order to improve the safety, durability, elasticity, biocompatibility, and clinical efficacy of tissue-engineered skin, several powerful seed cells have already found their application in wound repair, and a variety of bioactive scaffolds have been discovered to influence cell fate in epidermogenesis. These exuberant interests provide insights into advanced construction strategies for complex skin mimics. Based on these exciting developments, a complete full-thickness tissue-engineered skin is likely to be generated.

不同生物材料补片在治疗腹股沟嵌顿疝的临床疗效比较

目的比较不同生物材料补片在治疗腹股沟嵌顿疝的临床疗效。方法选取2019年2月-2020年4月偃师市中医院收治的90例腹股沟嵌顿疝患者,按随机数字法分为A、B、C三组。A组行传统手术,B、C组进行开放式无张力疝修补术,其中B组使用人体真皮脱皮细胞基质补片,C组选用猪小肠粘膜下层生物补片。比较三组手术与住院时间、术后血清肿发生率,并进行3个月随访,比较三组病情复发情况。结果A组手术时间短于B、C组(P<0.05),三组住院时间差异无统计学意义(P>0.05)。C组术后血清肿发生率高于A、B组(P<0.05),B、C组腹股沟疼痛、手术部位感染发生率低于A组(P<0.05)。随访结果显示,A组复发率高于B、C组(P<0.05)。结论人体真皮脱皮细胞基质补片和猪小肠粘膜下层生物补片均可有效降低腹股沟嵌顿疝患者术后复发率,其中猪小肠粘膜下层生物补片易发生血清肿可能,临床可根据患者实际情况选择性使用。

Accelerated neutral atom beam(ANAB)and gas clustered ion beam(GCIB)treatment of implantable device polymers leads to decreased bacterial attachment in vitro and decreased inflammation in vivo

Infections at the placement site of biomaterial-based devices and subsequent scar formation results in morbidity,which may require revision surgery.Biomaterials intended for permanent implantation in the body need to be biologically inert to avoid excessive foreign body response and to reduce bacterial attachment.In this study,we show that polymeric materials commonly used in medical devices,including polyetheretherketone(PEEK)and polypropylene,treated by gas cluster ion beam(GCIB)or by accelerated neutral atom beam(ANAB)result in a nanoscale-modified surface topography that changes the ability of extracellular proteins to bind.This leads to decreased bacterial attachment and an attenuated inflammatory response using both in vitro and in vivo assays.Differential adsorption of extracellular proteins to the polymeric surface improved the competitive attachment of osteoblasts over bacteria,without resorting to growth factor of antibiotic use.