Blood-derived biomaterials: fibrin sealant,platelet gel and platelet fibrin glue

Blood-derived biomaterials include fibrin sealant (FS) (also called fibrin glue), platelet gel (PG), and platelet fibrin glue. They are used in many surgical fields because of their functional properties and unique physical advantages compared to synthetic products. FS can be made industrially by the fractionation of large plasma pools, or from single plasma donations. Thanks to a high content in fibrinogen, FS exhibits, after activation by thrombin and formation of a strong fibrin clot, tissue sealing and haemostatic properties. PG and platelet fibrin glue are made from single blood donations (platelet concentrates combined or not with cryoprecipitate). Owing to their richness in platelet, PG and PFG can release, upon thrombin activation, a myriad of growth factors that can stimulate cell growth and differentiation, generating much interest for hard and soft tissues regeneration and healing, as well as, increasingly, cell therapy protocols to replace fetal bovine serum. Blood-derived biomaterials have the advantages, over synthetic glues and other biomaterials, of being physiologically compatible with human tissues, and of not inducing tissue necrosis or other tissue reactions. They can be readily colonized by cells and are totally biodegradable in a matter of days to weeks. These blood-derived biomaterials are used increasingly as tissue engineering tools, allowing surgeons to influence and improve the in vitro or in vivo cellular environment to enhance the success of tissue grafting. We review here the three main types of biomaterials that can be made from human blood and describe their biochemical and physiological properties as well as their clinical applications.     

Repair of articular cartilage defect by cell transplantation

Full-thickness articular cartilage defects are a major clinical problem; however, at present there is no treatment that is widely accepted to regeneratively repair these lesions. The current therapeutic approach is to drill or abrade the base of the defect to expose the bone marrow with its cells and growth factors. This usually results in a repaired tissue of fibrocartilage that functions poorly in the loaded joint environment. Recently, autologous cultured chondrocyte transplantation and mosaic plasty were explored. We can repair small articular cartilage defects using these methods, although their effectiveness is still controversial. We have reported that transplantation of allogeneic chondrocytes embedded in collagen gels or allogeneic chondrocytes cultured in collagen gels could repair articular cartilage defect in a rabbit model. We also reported that autologous culture-expanded bone marrow mesenchymal cell transplantation could repair articular cartilage defect in a rabbit model. This procedure offers expedient clinical use, given that autologous bone marrow cells are easily obtained and can be culture-expanded. We transplanted autologous culture-expanded bone marrow cells into the cartilage defect of the osteoarthritic knee joint on 11 patients at the time of high tibial osteotomy. As early as 6.8 weeks after transplantation, the defect was covered with white soft tissue, in which slight metachromasia was histologically observed. Thirty-three weeks after transplantation, the repaired tissue had hardened. Histologically, repaired tissues showed stronger metachromasia and a partial hyaline cartilage-like appearance. This procedure may prove a promising method by which to repair articular cartilage defects.     

Characteristics of platelet gels combined with silk

Platelet gel, a fibrin network containing activated platelets, is widely used in regenerative medicine due the capacity of platelet-derived growth factors to accelerate and direct healing processes. However, limitations to this approach include poor mechanical properties, relatively rapid degradation, and the lack of control of release of growth factors at the site of injection. These issues compromise the ability of platelet gels for sustained function in regenerative medicine. In the present study, a combination of platelet gels with silk fibroin gel was studied to address the above limitations. Mixing sonicated silk gels with platelet gels extended the release of growth factors without inhibiting gel-forming ability. The released growth factors were biologically active and their delivery was modified further by manipulation of the charge of the silk protein. Moreover, the silk gel augmented both the rheological properties and compressive stiffness of the platelet gel, tuned by the silk concentration and/or silk/platelet gel ratio. Silk-platelet gel injections in nude rats supported enhanced cell infiltration and blood vessel formation representing a step towards new platelet gel formulations with enhanced therapeutic impact.     

生物蛋白胶复合骨髓间充质干细胞修复兔多层软组织缺损

背景：符合软组织生理结构的生物蛋白胶适合作为修复软组织缺损的载体材料。 目的：观察生物蛋白胶复合骨髓间充质干细胞修复软组织缺损的可行性。 方法：在新西兰大白兔大腿处造成深达肌肉层,直径大于3 cm的软组织缺损。将24只新西兰大白兔随机分为3组,实验组将同种异体来源的骨髓间充质干细胞复合生物蛋白胶注射到软组织缺损处,对照组将生物蛋白胶注射到软组织缺损处,模型组造模后不注射。 结果与结论：术后14,21 d创面收缩率,实验组>对照组>模型组(P < 0.01);愈合时间,实验组<对照组<模型组(P < 0.01)。结果显示以生物蛋白胶为载体复合骨髓间充质干细胞能快速的修复多层软组织缺损。     

Fibrin: a versatile scaffold for tissue engineering applications

Tissue engineering combines cell and molecular biology with materials and mechanical engineering to replace damaged or diseased organs and tissues. Fibrin is a critical blood component responsible for hemostasis, which has been used extensively as a biopolymer scaffold in tissue engineering. In this review we summarize the latest developments in organ and tissue regeneration using fibrin as the scaffold material. Commercially available fibrinogen and thrombin are combined to form a fibrin hydrogel. The incorporation of bioactive peptides and growth factors via a heparin-binding delivery system improves the functionality of fibrin as a scaffold. New technologies such as inkjet printing and magnetically influenced self-assembly can alter the geometry of the fibrin structure into appropriate and predictable forms. Fibrin can be prepared from autologous plasma, and is available as glue or as engineered microbeads. Fibrin alone or in combination with other materials has been used as a biological scaffold for stem or primary cells to regenerate adipose tissue, bone, cardiac tissue, cartilage, liver, nervous tissue, ocular tissue, skin, tendons, and ligaments. Thus, fibrin is a versatile biopolymer, which shows a great potential in tissue regeneration and wound healing.     

Mesenchymal stromal cells form vascular tubes when placed in fibrin sealant and accelerate wound healing in vivo

Non-healing, chronic wounds are a growing public health problem and may stem from insufficient angiogenesis in affected sites. Here, we have developed a fibrin formulation that allows adipose-derived mesenchymal stromal cells (ADSCs) to form tubular structures in vitro. The tubular structures express markers of endothelium, including CD31 and VE-Cadherin, as well as the pericyte marker NG2. The ability for the MSCs to form tubular structures within the fibrin gels was directly dependent on the stoichiometric ratios of thrombin and fibrinogen and the resulting gel concentration, as well as on the presence of bFGF. Fibrin gel formulations that varied in stiffness were tested. ADSCs that are embedded in a stiff fibrin formulation express VE-cadherin and CD31 as shown by PCR, FACS and immunostaining. Confocal imaging analysis demonstrated that tubular structures formed, containing visible lumens, in the stiff fibrin gels in vitro. There was also a difference in the amounts of bFGF secreted by ADSCs grown in the stiffer gels as compared to softer gels. Additionally, hAT-MSCs gave rise to perfusable vessels that were VE-cadherin positive after subcutaneous injection into mice, whereas the softer fibrin formulation containing ADSCs did not. The application of ADSCs delivered in the stiff fibrin gels allowed for the wounds to heal more quickly, as assessed by wound size, amount of granulation tissue and collagen content. Interestingly, following 5 days of healing, the ADSCs remained within the fibrin gel and did not integrate into the granulation tissue of healing wounds in vivo. These data show that ADSCs are able to form tubular structures within fibrin gels, and may also contribute to faster wound healing, as compared with no treatment or to wounds treated with fibrin gels devoid of ADSCs.     

Severe blood loss during spinal reconstructive procedures: the potential usefulness of topical hemostatic agents

Complex spinal reconstructive procedures are invariably associated with excessive intraoperative blood loss that significantly increases the risk of severe perioperative complications. In some cases, excessive hemorrhage is equivalent to estimated total blood volume. Unfortunately, widely exposed bony surfaces are not amenable to standard hemostatic maneuvers utilized during soft tissue surgery. This article evaluates the clinical effectiveness of several approaches to blood management in this setting, and hypothesizes that underappreciated topical hemostatic agents may provide benefit by reducing the need for autologous predonation, banked donor blood or antifibrinolytic agents. Topical agents combining collagen, thrombin and fibrin have demonstrated initial promise by inducing platelet aggregation and initiating the clotting cascade when applied directly to bleeding bony sites. Clinical studies are clearly warranted.     

Injectable allogeneic bone mesenchymal stem cells: a potential minimally invasive therapy for atrophic nonunion

How to enhance atrophic nonunion repairing is a common challenge encountered in orthopaedic surgeons. With the increasing popularity of minimally invasive techniques, one of the major thrusts in treatment approaches for atrophic nonunions is to develop injectable systems that can shorten the surgical operation time, reduce the morbidity and costs for patients. Bone mesenchymal stem cells (BMSCs) may provide new strategies to treat atrophic nonunion because of their prolonged self-renewal capacity and ability to differentiate into osteogenic lineage under the proper conditions. However, providing an autologous BMSCs in the clinical setting is often limited, because the patient’s marrow is damaged or the cell yield from healthy marrow is reduced. Due to the limitation of autologous BMSCs in clinical application, we turn to consider allogeneic BMSCs as seeding cells in atrophic nonunion repair. Allogeneic BMSCs could are isolated from one or more donors would have the potential to be expanded and cryopreserved for future use. Previous studies have indicated that BMSCs possess immune-privileged properties, which avoid or actively suppress the immunological responses. Here we propose the hypothesis that the application of osteo-induced allogeneic BMSCs in fibrin gels for delivery of the cells by means of an injectable device would enhance repair of atrophic nonunion without the use of immunosuppressive therapy. Furthermore, fibrin gel could be useful as BMSCs carrier to deliver cells in vivo, there is no immunogenicity to be expected and BMSCs were able to spread and proliferate into the fibrin. Therefore, if the hypothesis is proved to be practical, it might represent a novel minimally invasive therapeutic approach and enhance atrophic nonunion repairing.     

输血支持在造血干细胞移植中的应用

背景：接受造血干细胞移植的患者经常需要血液制品输注支持,而患者对红细胞和血小板输注的需求差异非常大,这主要依赖于造血干细胞移植的类型和患者本身的疾病性质。 目的：评价中山大学附属中山医院接受造血干细胞移植患者移植期间输血的需求和数量。 方法：收集中山大学附属中山医院2004-01/2010-06接受造血干细胞移植患者的资料,包括移植的适应证、移植的类型、CD34+细胞的数量、红细胞和血小板的输注数量、费用、脱离输注时间以及中性粒细胞和血小板植入时间;红细胞输注的阈值是血红蛋白计数为70 g/L,而血小板的输注阈值是计数为20×10⁹ L^-1。研究分析了患者移植期间红细胞和血小板输注的需求、输注量、输血费用,以及患者的生存情况。 结果与结论：自体造血干细胞移植组中有14例(93%)患者,而异基因造血干细胞移植组中有35例(90%)患者显示了造血细胞植入和脱离输注证据。自体造血干细胞移植组取得脱离红细胞输注天数为14.6 d,明显短于异基因造血干细胞移植组。与异基因造血干细胞移植组比较,自体造血干细胞移植组红细胞输注单位明显减少;而异基因造血干细胞移植组的红细胞输注费用明显高于自体造血干细胞移植组。输血花费昂贵,但却是造血干细胞移植中必不可少的一部分,异基因造血干细胞移植组需要更多的输血支持。脱离输注时间有望成为评估造血干细胞移植成功的指标。     

Platelet biology in regenerative medicine of skeletal muscle

Platelet‐based applications such as platelet‐rich plasma (PRP) and platelet releasate have gained unprecedented attention in regenerative medicine across a variety of tissues as of late. The rationale behind utilizing PRP originates in the delivery of key cytokines and growth factors from α‐granules to the targeted area, which in turn act as cell cycle regulators and promote the healing process across a variety of tissues. The aim of the present review is to assimilate current experimental evidence on the role of platelets as biomaterials in tissue regeneration, particularly in skeletal muscle, by integrating findings from human, animal and cell studies. This review is composed of 3 parts: firstly, we review key aspects of platelet biology that precede the preparation and use of platelet‐related applications for tissue regeneration. Secondly, we critically discuss relevant evidence on platelet‐mediated regeneration in skeletal muscle focusing on findings from (i) clinical trials, (ii) experimental animal studies and (iii) cell culture studies; and thirdly, we discuss the application of platelets in the regeneration of several other tissues including tendon, bone, liver, vessels and nerve. Finally, we review key technical variations in platelet preparation that may account for the large discrepancy in outcomes from different studies. This review provides an up‐to‐date reference tool for biomedical and clinical scientists involved in platelet‐mediated tissue regenerative applications.     

Influence of platelet-derived growth factor-AB on tissue development in autologous platelet-rich plasma gels

Fibrin-based scaffolds are widely used in tissue engineering. We postulated that the use of platelet-rich plasma (PRP) in contrast to platelet-poor plasma and pure fibrinogen as the basic material leads to an increased release of autologous platelet-derived growth factor (PDGF)-AB, which may have a consequent positive effect on tissue development. Therefore, we evaluated the release of PDGF-AB during the production process and the course of PDGF release during cultivation of plasma gels with and w/o platelets. The influence of PDGF-AB on the proliferation rate of human umbilical cord artery smooth muscle cells (HUASMCs) was studied using XTT assay. The synthesis of extracellular matrix by HUASMCs in plasma- and fibrin gels was measured using hydroxyproline assay. The use of PRP led to an increase in autologous PDGF-AB release. Further, the platelet-containing plasma gels showed a prolonged release of growth factor during cultivation. Both PRP and platelet-poor plasma gels had a positive effect on the production of collagen. However, PDGF-AB as a supplement in medium and in pure fibrin gel had neither an effect on cell proliferation nor on the collagen synthesis rate. This observation may be due to an absence of PDGF receptors in HUASMCs as determined by flow cytometry. In conclusion, although the prolonged autologous production of PDGF-AB in PRP gels is possible, the enhanced tissue development by HUASMCs within such gels is not PDGF related.     

Discrete crosslinked fibrin microthread scaffolds for tissue regeneration

In this study, we report on the development of discrete fibrin microthreads as well as novel scaffolds composed of arrays of fibrin threads. These scaffolds exhibit mechanical properties that are significantly greater than fibrin gels and cellular responses suggesting that the materials are conducive to the development of organized, aligned tissues. Fibrin microthreads were produced by coextruding solutions of 70 mg/mL fibrinogen and 6 U/mL thrombin through small diameter polyethylene tubing. Uncrosslinked fibrin microthreads averaged 55-65 microm in hydrated diameter and achieved ultimate tensile strengths approaching 4.5 MPa. The strengths and stiffnesses of the microthreads were approximately twofold greater when the materials were treated with exposure to ultraviolet (UV) light. Although UV crosslinking attenuated fibroblast proliferation, uncrosslinked fibrin microthreads supported fibroblast attachment, proliferation, and alignment, suggesting that they represent a viable biomaterial for the aligned regeneration of tissues. Because of the physiologic roles of fibrin matrices in the early phase of wound healing, we anticipate that these fibrin-based microthreads will direct the spatially and temporally complex processes of cell-mediated tissue ingrowth and regeneration.     

Choukroun富血小板纤维蛋白在口腔种植骨缺损中的研究与进展

背景：近年来,Choukroun富血小板纤维蛋白作为一种富含自体细胞因子和生长因子的新型生物材料,在口腔种植骨缺损的临床应用中受到了广泛关注。 目的：就富血小板纤维蛋白的实验及临床研究进展进行综述。 方法：由第一作者应用计算机检索PubMed数据库及中国期刊网全文数据库2000-01/2011-12有关富血小板纤维蛋白生物学特性、实验研究以及临床应用等方面的文章,英文检索词为“choukroun’s platelet-rich fibrin,platelet-rich plasma,dental implant,bone defect,GBR”,中文检索词为“富血小板纤维蛋白,富血小板血浆,口腔种植,骨缺损,引导骨再生”。排除重复性研究,共保留30篇文献进行综述。 结果与结论：富血小板纤维蛋白由纤维蛋白网、血小板及粒细胞等组成,是目前较为先进的一种富含成骨作用因子的血液制品。具有制备过程操作简单、不需要添加其他制剂的特点,同时还有效模拟生理状态下血凝块中纤维蛋白的形成,与人体正常血凝块中的纤维蛋白相似,并很好地避免了免疫排斥和交叉感染的发生。在实验研究及临床应用中均显示了很好的促进组织愈合的能力。加之其成本低廉、取材方便等优点,在今后的口腔种植领域将得到越来越多的关注。     

造血干细胞移植与血小板输注

背景：血小板输注被认为是对致死性出血最为有效的治疗措施,已成为治疗造血干细胞移植后血小板减少的标准方法。关于血小板输注临床应用的相关研究资料相对缺乏,各医院间实际情况变化较大。 目的：对52例造血干细胞移植患者移植期间血小板输注的情况进行回顾性分析。 方法：将出现活动性出血所进行的血小板输注归为治疗性输注,在没有出血表现的情况下进行的血小板输注定义为预防性输注。根据24 h血小板回收率和出血改善情况来评价不同血小板输注性质、自体或异基因移植类型等因素对血小板输注疗效的影响。 结果与结论：预防性和治疗性血小板输注有效率分别为63.6%和55.6%;接受造血干细胞移植患者血小板输注有效率和平均血小板升高值分别为60.9%和26.8×10⁹ L^-1。而自体造血干细胞移植组和异基因造血干细胞移植组间预防性和治疗性输注的疗效无差别。回归分析中,凝血功能异常被认为是影响血小板输注疗效的独立风险因素。     

Platelet‐rich plasma (PRP) and platelet derivatives for topical therapy. What is true from the biologic view point?

Background PubMed accessed on January 23 revealed 160 items about ‘platelet gel or releasate’ associated to topical therapy. Yahoo! provided 8580 items; Altavista 8650; Google 25 300. Companies providing blood separators are going to offer devices to prepare platelet‐rich plasma (PRP) for topical therapy. Several devices are filling the marketplace aiming to produce platelet gels for human therapy. Never‐ending lists of clinical conditions supposed to benefit from platelet gel application are published. Clinical benefits include bactericidal activity, pain reduction, tissue repair and regeneration. Are platelet derivatives the magic bullet for topical therapy? Methods Many in vitro studies account for clinical benefit from platelet gel. Several in vivo studies provide clinical evidence about healing of tissue repair induced by platelet derivatives. Nevertheless, systematic reviews reveal inadequate studies providing enough methodological strength to confirm evidence‐based efficacy. At present we must deal the subject with care using mostly inductive criteria. Only reproducible scientific data are to be considered. Every effort should be made for commercial, private and personal popularity‐related scenarios to be rejected from our consideration. Sometimes, this is not so simple to be done. Results There is a list of more than 60 biologically active platelet‐derived factors directly involved in tissue repair mechanisms: chemotaxis, cell proliferation, angiogenesis, extracellular matrix deposition and remodelling. Biological functions are also indirectly mediated by platelet‐derived growth factors; such functions are triggered by chemokines and cytokines produced by bystander cells such as fibroblasts, macrophages, endothelial cells, lymphocytes, under platelet‐derived factor stimulation. All of this is well demonstrated. Clinical studies endorsed with stringent randomized controlled trials are lacking. However, several serious studies have been published reporting clinical efficacy of platelet derivatives in many clinical areas. Considering these papers seriously, we maintain that in most cases, clinical efficacy is by far more than just a suggestion. Discussion Although we consider evidence‐based medicine (EBM) highly meaningful, we emphasize that medicine moved forwards also before EBM was conceived. We do not consider platelet gel and releasate such as a ‘magic bullet’, but we are strongly impressed by the results our group, and other groups have obtained treating a variety of tissue lesions in a variety of clinical conditions. Clinical benefits are a composite result of the lesion state, severity and duration, coexisting pathologies, patient's age and product characteristics. From our point of view, the last is a pivotal variable that has strong influence over the clinical outcome. Platelet‐rich plasma, platelet gel and platelet releasate need stringent definitions. Too many methods are used to prepare these products. Both methods and product need definition, validation, specific quality parameters and clinical indications. Further biologic and biochemical studies are needed as well to understand (if possible to modulate) the inner mechanisms of healing induced by topical treatment with platelet derivatives.     

Collagen composite biomaterials resist contraction while allowing development of adipocytic soft tissue in vitro

Soft tissue defects resulting from tumor resection or trauma require surgery to restore the body's contours. Because autologous tissues or synthetic implant reconstructions can be less than ideal, engineered tissues produced in vitro are being developed as alternatives. Collagen gels have been proposed for this application because they are biocompatible and can be shaped to fill a specific defect. In the present study, constructs of collagen gels with embedded short collagen fibers (which are more permeable than plain collagen gels and which maintain size and shape in culture) were seeded with preadipocytes and cultured in vitro. The addition of increasing volume fractions of embedded fibers limited cell-mediated contraction of the constructs. Including epithelial cell-seeded collagen gel layers resulted in more contraction, but still less than that observed in constructs without fibers. Constructs with embedded collagen fibers contained significantly more cells at all time points examined when compared to constructs without embedded fibers. Mature adipocytes were observed throughout constructs after 21 days in culture; spectroscopic analyses indicated lipid inclusion in constructs seeded with preadipocytes, which differed from analyses of natural porcine adipose tissue. These results support the promise of collagen composites as a biomaterial for use in producing soft tissues in vitro.     

Outgrowth endothelial cells isolated and expanded from human peripheral blood progenitor cells as a potential source of autologous cells for endothelialization of silk fibroin biomaterials

One challenge of particular importance in tissue engineering is to improve vascularization of larger size defects, which would then facilitate a sufficient supply with oxygen and nutrients to the central regions of a larger tissue-engineered construct or in highly vascularized tissues. In this study, we show that outgrowth endothelial cells (OECs) derived from human peripheral blood can serve as a source of human autologous endothelial cells and can be used in combination with fibroin silk fiber meshes for applications in tissue engineering. OEC reveal a highly differentiated endothelial phenotype as well as a high phenotypic stability during their expansion. Furthermore, OEC showed very promising results in the endothelialization of fibroin silk fiber meshes, maintaining their endothelial characteristics and functions. On the fibroin fiber meshes OECs formed differentiated endothelial cell layers covering the single fibers as shown by data from scanning electron microscopy, immunofluorescence, and gene expression analysis. After embedding in a wound-healing matrix, mimicked by fibrin gels, OEC migrated from the fibroin scaffolds into the fibrin and formed a microvessel-like network. Thus, we conclude that OEC could serve as a valuable source of autologous endothelial cells, supporting pro-angiogenic therapies in combination with silk fibroin-based scaffolding materials in the field of tissue engineering and regenerative medicine.     

Biomimetic delivery of keratinocyte growth factor upon cellular demand for accelerated wound healing in vitro and in vivo

Exogenous keratinocyte growth factor (KGF) significantly enhances wound healing, but its use is hampered by a short biological half-life and lack of tissue selectivity. We used a biomimetic approach to achieve cell-controlled delivery of KGF by covalently attaching a fluorescent matrix-binding peptide that contained two domains: one recognized by factor XIII and the other by plasmin. Modified KGF was incorporated into the fibrin matrix at high concentration in a factor XIII-dependent manner. Cell-mediated activation of plasminogen to plasmin degraded the fibrin matrix and cleaved the peptides, releasing active KGF to the local microenvironment and enhancing epithelial cell proliferation and migration. To demonstrate in vivo effectiveness, we used a hybrid model of wound healing that involved transplanting human bioengineered skin onto athymic mice. At 6 weeks after grafting, the transplanted tissues underwent full thickness wounding and treatment with fibrin gels containing bound KGF. In contrast to topical KGF, fibrin-bound KGF persisted in the wounds for several days and was released gradually, resulting in significantly enhanced wound closure. A fibrinolytic inhibitor prevented this healing, indicating the requirement for cell-mediated fibrin degradation to release KGF. In conclusion, this biomimetic approach of localized, cell-controlled delivery of growth factors may accelerate healing of large full-thickness wounds and chronic wounds that are notoriously difficult to heal.     

Autologous fibrin matrices: a potential source of biological mediators that modulate tendon cell activities

The use of autologous fibrin matrices has been proposed as a therapeutic strategy for the local and physiological delivery of growth factors in the treatment of several clinical conditions requiring tendon healing or tendon graft remodelling. In the present work, we investigated the proliferation, synthesis of type-I collagen and angiogenic factors by tendon cells seeded on platelet-rich (PR) and platelet-poor (PP) matrices. Furthermore, in vivo cellular and vascular effects of each treatment were examined after infiltration in Achilles tendon in sheep. Results showed that the presence of platelets within the fibrin matrices increased significantly the proliferation of tendon cells. Additionally, cultured tendon cells synthesised type I collagen and angiogenic factors such as VEGF and HGF. The synthesis of VEGF, but not of HGF, was significantly higher when platelets were present within the matrix. In the sheep model, the injection of pre-clotted plasma within tendons increased cellular density and promoted neovascularization. These results indicate that administration of fibrin matrices is a safe and easy strategy that may open new avenues for enhancing tissue healing and remodelling and influences the process of regeneration in clinical situations characterised by a poor healing outcome.     

改良型富血小板纤维蛋白膜包裹颗粒软骨移植的长期组织学改变

文题释义：改良型富血小板纤维蛋白膜：是第二代富血小板浓缩制品富血小板纤维蛋白通过低速延时的方法得到的改良型富血小板纤维蛋白凝胶,再经过压制后得到的一种具有一定韧性的膜状物,可起到包裹作用,有利于细胞的增殖分化。 颗粒软骨移植：将自体软骨切成1.0-2.0 mm的颗粒状后移植于受区,但术后远期存在移植物吸收、变形等风险,目前国内外关于有效减少颗粒软骨移植后并发症等风险的报道仍然较少。背景：已有学者研究并制备了改良型富血小板纤维蛋白,并通过动物实验证实了改良型富血小板纤维蛋白可以促进自体软硬组织的再生与修复。目的：制备改良型富血小板纤维蛋白膜,观察改良型富血小板纤维蛋白膜及自体筋膜包裹颗粒软骨移植术后移植物的组织学改变。 方法：新西兰雄兔12只,均进行以下相同手术流程：制备改良型富血小板纤维蛋白膜,取兔左耳软骨组织及右后肢自体筋膜组织,制备成3种移植物：颗粒软骨;自体筋膜包裹颗粒软骨;改良型富血小板纤维蛋白膜包裹颗粒软骨。将移植物分别回植于兔背部皮下,术后4个月取出移植物,进行一般形态观察和组织病理学检测。 结果与结论：①自体筋膜和改良型富血小板纤维蛋白膜包裹颗粒软骨移植物厚度较颗粒软骨移植物厚,移植物外形较圆润,表面较平整;②改良型富血小板纤维蛋白膜包裹颗粒软骨移植物软骨细胞存活率和再生潜力明显优于另外2种移植物(P < 0.05);其他组织学参数各组之间无显著差异;③结果说明：改良型富血小板纤维蛋白膜包裹颗粒软骨移植能够提高颗粒软骨存活率和移植物塑形效果,减少移植后软骨再吸收。ORCID:0000-0002-4733-9912(杨银辉) 中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程