The induction of bone formation by 3D-printed PLGA microsphere scaffolds in a calvarial orthotopic mouse model: a pilot study.

IF 4.3 3区 工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Frontiers in Bioengineering and Biotechnology Pub Date : 2024-10-25 eCollection Date: 2024-01-01 DOI:10.3389/fbioe.2024.1425469
Roland M Klar, James C Cox, Claire J Houchen, Naren Raja, Houssam Bouloussa, Stefan Lohfeld
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引用次数: 0

Abstract

Polymeric biodegradable microspheres are readily utilized to support targeted drug delivery for various diseases clinically. 3D printed tissue engineering scaffolds from polymer filaments with embedded microspheres or nanoparticles, as well as bulk microsphere scaffolds, have been investigated for regenerative medicine and tissue engineering. However, 3D printed scaffolds consisting only of a homogenous microsphere size with an optimized architecture that includes a unique micro- and macroporosity, have been challenging to produce and hence, have not been assessed in the literature yet. Utilizing our recently established 3D-MultiCompositional Microsphere-Adaptive Printing (3D-McMap) method, the present study evaluated the effectiveness of 3D-printed poly (lactic-co-glycolic acid) (PLGA) microsphere scaffolds, consisting of microsphere sizes 50, 100, or 200 μm, on the induction of bone formation when implanted in the calvarial murine regeneration model. Our results showed that PLGA microsphere scaffolds possess unique properties that support bone regeneration by supporting osteoconduction and stimulating, in our opinion, true spontaneous osteoinduction. The study demonstrated that PLGA microsphere-based scaffolds support bone growth in the absence of additional growth factors and promote osteogenesis primarily via their unique geometric configuration. The larger the microspheres were, the greater de novo bone formation was. This proves that bone tissue engineering scaffolds 3D printed from microspheres, enabled by the 3D-McMap method, are superior over bulk material printed scaffolds, as they possess the unique capability of spontaneous induction of new bone formation. With the addition of encapsulated modulatory bone-forming biomolecules they can substantially improve the spatiotemporal control of tissue morphogenesis, potentially leading to new innovative clinical tissue repair therapies that regenerate bone in large defects correctly and fully.

三维打印聚乳酸(PLGA)微球支架在小鼠腓骨正位模型中诱导骨形成的试验研究。
聚合物生物可降解微球可用于支持临床上各种疾病的靶向给药。人们已经研究了由嵌入微球或纳米颗粒的聚合物丝制成的三维打印组织工程支架,以及块状微球支架,用于再生医学和组织工程。然而,三维打印支架仅由具有独特微孔和大孔的优化结构的均匀微球组成,其生产具有挑战性,因此尚未在文献中进行评估。本研究利用我们最近建立的三维多成分微球自适应打印(3D-McMap)方法,评估了三维打印聚(乳酸-共聚-乙醇酸)(PLGA)微球支架(微球尺寸为 50、100 或 200 μm)植入小鼠腓肠肌再生模型时诱导骨形成的效果。我们的研究结果表明,PLGA 微球支架具有独特的特性,可通过支持骨诱导和刺激(我们认为)真正的自发骨诱导来支持骨再生。研究表明,在没有额外生长因子的情况下,PLGA 微球支架能支持骨生长,并主要通过其独特的几何结构促进骨生成。微球越大,新生骨形成越多。这证明,利用 3D-McMap 方法用微球三维打印的骨组织工程支架优于大块材料打印的支架,因为它们具有自发诱导新骨形成的独特能力。通过添加封装的调节骨形成的生物大分子,它们可以大大改善对组织形态发生的时空控制,从而有可能开发出新的创新型临床组织修复疗法,在大面积缺损中正确、全面地再生骨骼。
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来源期刊
Frontiers in Bioengineering and Biotechnology
Frontiers in Bioengineering and Biotechnology Chemical Engineering-Bioengineering
CiteScore
8.30
自引率
5.30%
发文量
2270
审稿时长
12 weeks
期刊介绍: The translation of new discoveries in medicine to clinical routine has never been easy. During the second half of the last century, thanks to the progress in chemistry, biochemistry and pharmacology, we have seen the development and the application of a large number of drugs and devices aimed at the treatment of symptoms, blocking unwanted pathways and, in the case of infectious diseases, fighting the micro-organisms responsible. However, we are facing, today, a dramatic change in the therapeutic approach to pathologies and diseases. Indeed, the challenge of the present and the next decade is to fully restore the physiological status of the diseased organism and to completely regenerate tissue and organs when they are so seriously affected that treatments cannot be limited to the repression of symptoms or to the repair of damage. This is being made possible thanks to the major developments made in basic cell and molecular biology, including stem cell science, growth factor delivery, gene isolation and transfection, the advances in bioengineering and nanotechnology, including development of new biomaterials, biofabrication technologies and use of bioreactors, and the big improvements in diagnostic tools and imaging of cells, tissues and organs. In today`s world, an enhancement of communication between multidisciplinary experts, together with the promotion of joint projects and close collaborations among scientists, engineers, industry people, regulatory agencies and physicians are absolute requirements for the success of any attempt to develop and clinically apply a new biological therapy or an innovative device involving the collective use of biomaterials, cells and/or bioactive molecules. “Frontiers in Bioengineering and Biotechnology” aspires to be a forum for all people involved in the process by bridging the gap too often existing between a discovery in the basic sciences and its clinical application.
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