Chiara Rinoldi, Ph.D., Eng.

Department of Biosystems and Soft Matter (ZBiMM)
Division of Modelling in Biology and Medicine (PMBM)
position: assistant
telephone: (+48) 22 826 12 81 ext.: 330
room: 320
e-mail: crinoldi

Recent publications
1.Fallahi A., Yazdi I., Serex L., Lasha E., Faramarzi N., Tarlan F., Avci H., Almeida R., Sharifi F., Rinoldi C., Gomes M.E., Shin S.R., Khademhosseini A., Akbari M., Tamayol A., Customizable composite fibers for engineering skeletal muscle models, ACS BIOMATERIALS SCIENCE & ENGINEERING, ISSN: 2373-9878, DOI: 10.1021/acsbiomaterials.9b00992, Vol.6, No.2, pp.1112-1123, 2020
Abstract:

Engineering tissue-like scaffolds that can mimic the microstructure, architecture, topology, and mechanical properties of native tissues while offering an excellent environment for cellular growth has remained an unmet need. To address these challenges, multi-compartment composite fibers are fabricated. These fibers can be assembled through textile processes to tailor tissue-level mechanical and electrical properties independent of cellular level components. Textile technologies also allow controlling the distribution of different cell types and microstructure of fabricated constructs and directing cellular growth within 3D microenvironment. Here, we engineered composite fibers from biocompatible cores and biologically relevant hydrogel sheaths. The fibers are mechanically robust to be assembled using textile processes and could support adhesion, proliferation and maturation of cell populations important for engineering of skeletal muscles. We also demonstrated that the changes in the electrical conductivity of the multi-compartment fibers could significantly enhance myogenesis in vitro.

Keywords:

reinforced fibers, biotextiles, tissue engineering, organ weaving, interpenetrating network hydrogels, skeletal muscles

Affiliations:
Fallahi A.-Paul Scherrer Institut (CH)
Yazdi I.-Massachusetts Institute of Technology (US)
Serex L.-Brigham and Women's Hospital (US)
Lasha E.-Brigham and Women's Hospital (US)
Faramarzi N.-Brigham and Women's Hospital (US)
Tarlan F.-Brigham and Women's Hospital (US)
Avci H.-Eskisehir Osmangazi University (TR)
Almeida R.-Brigham and Women's Hospital (US)
Sharifi F.-Massachusetts Institute of Technology (US)
Rinoldi C.-other affiliation
Gomes M.E.-University of Minho (PT)
Shin S.R.-Massachusetts Institute of Technology (US)
Khademhosseini A.-Massachusetts Institute of Technology (US)
Akbari M.-Brigham and Women's Hospital (US)
Tamayol A.-Massachusetts Institute of Technology (US)
2.Pawłowska S., Rinoldi C., Nakielski P., Ziai Y., Urbanek O., Li X., Kowalewski T.A., Ding B., Pierini F., Ultraviolet light‐assisted electrospinning of core–shell fully cross‐linked P(NIPAAm‐co‐NIPMAAm) hydrogel‐based nanofibers for thermally induced drug delivery self‐regulation, Advanced Materials Interfaces, ISSN: 2196-7350, DOI: 10.1002/admi.202000247, Vol.7, No.12, pp.2000247-1-13, 2020
Abstract:

Body tissues and organs have complex functions which undergo intrinsic changes during medical treatments. For the development of ideal drug delivery systems, understanding the biological tissue activities is necessary to be able to design materials capable of changing their properties over time, on the basis of the patient's tissue needs. In this study, a nanofibrous thermal‐responsive drug delivery system is developed. The thermo‐responsivity of the system makes it possible to self‐regulate the release of bioactive molecules, while reducing the drug delivery at early stages, thus avoiding high concentrations of drugs which may be toxic for healthy cells. A co‐axial electrospinning technique is used to fabricate core–shell cross‐linked copolymer poly(N‐isopropylacrylamide‐co‐N‐isopropylmethacrylamide) (P(NIPAAm‐co‐NIPMAAm)) hydrogel‐based nanofibers. The obtained nanofibers are made of a core of thermo‐responsive hydrogel containing a drug model, while the outer shell is made of poly‐l‐lactide‐co‐caprolactone (PLCL). The custom‐made electrospinning apparatus enables the in situ cross‐linking of P(NIPAAm‐co‐NIPMAAm) hydrogel into a nanoscale confined space, which improves the electrospun nanofiber drug dosing process, by reducing its provision and allowing a self‐regulated release control. The mechanism of the temperature‐induced release control is studied in depth, and it is shown that the system is a promising candidate as a "smart" drug delivery platform.

Keywords:

biomimetic nanomaterials, electrospun core–shell nanofibers, hierarchical nanostructures, smart drug delivery, thermo‐responsive hydrogels

Affiliations:
Pawłowska S.-IPPT PAN
Rinoldi C.-IPPT PAN
Nakielski P.-IPPT PAN
Ziai Y.-IPPT PAN
Urbanek O.-IPPT PAN
Li X.-Donghua University (CN)
Kowalewski T.A.-IPPT PAN
Ding B.-Donghua University (CN)
Pierini F.-IPPT PAN
3.Rinoldi C., Costantini M., Kijeńska-Gawrońska E., Testa S., Fornetti E., Heljak M., Ćwiklińska M., Buda R., Baldi J., Cannata S., Guzowski J., Gargioli C., Khademhosseini A., Święszkowski W., Tendon tissue engineering: effects of mechanical and biochemical stimulation on stem cell alignment on cell‐laden hydrogel yarns, ADVANCED HEALTHCARE MATERIALS, ISSN: 2192-2659, DOI: 10.1002/adhm.201801218, Vol.8, No.7, pp.1801218-1-10, 2019
Abstract:

Fiber-based approaches hold great promise for tendon tissue engineering enabling the possibility of manufacturing aligned hydrogel filaments that can guide collagen fiber orientation, thereby providing a biomimetic micro-environment for cell attachment, orientation, migration, and proliferation. In this study, a 3D system composed of cell-laden, highly aligned hydrogel yarns is designed and obtained via wet spinning in order to reproduce the morphology and structure of tendon fascicles. A bioink composed of alginate and gelatin methacryloyl (GelMA) is optimized for spinning and loaded with human bone morrow mesenchymal stem cells (hBM-MSCs). The produced scaffolds are subjected to mechanical stretching to recapitulate the strains occurring in native tendon tissue. Stem cell differentiation is promoted by addition of bone morphogenetic protein 12 (BMP-12) in the culture medium. The aligned orientation of the fibers combined with mechanical stimulation results in highly preferential longitudinal cell orientation and demonstrates enhanced collagen type I and III expression. Additionally, the combination of biochemical and mechanical stimulations promotes the expression of specific tenogenic markers, signatures of efficient cell differentiation towards tendon. The obtained results suggest that the proposed 3D cell-laden aligned system can be used for engineering of scaffolds for tendon regeneration.

Keywords:

hydrogel fibers, static mechanical stretching, stem cell alignment, tenogenic differentiation, wet spinning

Affiliations:
Rinoldi C.-other affiliation
Costantini M.-Sapienza University of Rome (IT)
Kijeńska-Gawrońska E.-Warsaw University of Technology (PL)
Testa S.-Tor Vergata Rome University (IT)
Fornetti E.-Tor Vergata Rome University (IT)
Heljak M.-Warsaw University of Technology (PL)
Ćwiklińska M.-Institute of Physical Chemistry, Polish Academy of Sciences (PL)
Buda R.-Institute of Physical Chemistry, Polish Academy of Sciences (PL)
Baldi J.-Tor Vergata Rome University (IT)
Cannata S.-Tor Vergata Rome University (IT)
Guzowski J.-Institute of Physical Chemistry, Polish Academy of Sciences (PL)
Gargioli C.-Tor Vergata Rome University (IT)
Khademhosseini A.-Massachusetts Institute of Technology (US)
Święszkowski W.-other affiliation
4.Rinoldi C., Fallahi A., Yazdi I.K., Paras J.C., Kijeńska-Gawrońska E., Trujillo-de Santiago G., Tuoheti A., Demarchi D., Annabi N., Khademhosseini A., Święszkowski W., Tamayol A., Mechanical and biochemical stimulation of 3D multilayered scaffolds for tendon tissue engineering, ACS BIOMATERIALS SCIENCE & ENGINEERING, ISSN: 2373-9878, DOI: 10.1021/acsbiomaterials.8b01647, Vol.5, No.6, pp.2953-2964, 2019
Abstract:

Tendon injuries are frequent and occur in the elderly, young, and athletic populations. The inadequate number of donors combined with many challenges associated with autografts, allografts, xenografts, and prosthetic devices have added to the value of engineering biological substitutes, which can be implanted to repair the damaged tendons. Electrospun scaffolds have the potential to mimic the native tissue structure along with desired mechanical properties and, thus, have attracted noticeable attention. In order to improve the biological responses of these fibrous structures, we designed and fabricated 3D multilayered composite scaffolds, where an electrospun nanofibrous substrate was coated with a thin layer of cell-laden hydrogel. The whole construct composition was optimized to achieve adequate mechanical and physical properties as well as cell viability and proliferation. Mesenchymal stem cells (MSCs) were differentiated by the addition of bone morphogenetic protein 12 (BMP-12). To mimic the natural function of tendons, the cell-laden scaffolds were mechanically stimulated using a custom-built bioreactor. The synergistic effect of mechanical and biochemical stimulation was observed in terms of enhanced cell viability, proliferation, alignment, and tenogenic differentiation. The results suggested that the proposed constructs can be used for engineering functional tendons.

Keywords:

tendon tissue engineering, composite scaffolds, nanofibrous materials, mechanical stimulation, stem cell differentiation

Affiliations:
Rinoldi C.-other affiliation
Fallahi A.-Paul Scherrer Institut (CH)
Yazdi I.K.-Massachusetts Institute of Technology (US)
Paras J.C.-Massachusetts Institute of Technology (US)
Kijeńska-Gawrońska E.-Warsaw University of Technology (PL)
Trujillo-de Santiago G.-Massachusetts Institute of Technology (US)
Tuoheti A.-Politecnico di Torino (IT)
Demarchi D.-Politecnico di Torino (IT)
Annabi N.-Massachusetts Institute of Technology (US)
Khademhosseini A.-Massachusetts Institute of Technology (US)
Święszkowski W.-other affiliation
Tamayol A.-Massachusetts Institute of Technology (US)
5.Sardelli L., Pacheco D.P., Zorzetto L., Rinoldi C., Święszkowski W., Petrini P., Engineering biological gradients, Journal of Applied Biomaterials & Functional Materials, ISSN: 2280-8000, DOI: 10.1177/2280800019829023, Vol.17, No.1, pp.2280800019829023-1-15, 2019
Abstract:

Biological gradients profoundly influence many cellular activities, such as adhesion, migration, and differentiation, which are the key to biological processes, such as inflammation, remodeling, and tissue regeneration. Thus, engineered structures containing bioinspired gradients can not only support a better understanding of these phenomena, but also guide and improve the current limits of regenerative medicine. In this review, we outline the challenges behind the engineering of devices containing chemical-physical and biomolecular gradients, classifying them according to gradient-making methods and the finalities of the systems. Different manufacturing processes can generate gradients in either in-vitro systems or scaffolds, which are suitable tools for the study of cellular behavior and for regenerative medicine; within these, rapid prototyping techniques may have a huge impact on the controlled production of gradients. The parallel need to develop characterization techniques is addressed, underlining advantages and weaknesses in the analysis of both chemical and physical gradients.

Keywords:

graded scaffolds, rapid prototyping, bioinspired, microfluidic, gradient characterization, cartilage, bone

Affiliations:
Sardelli L.-Politecnico di Milano (IT)
Pacheco D.P.-Politecnico di Milano (IT)
Zorzetto L.-University of Liège (BE)
Rinoldi C.-other affiliation
Święszkowski W.-other affiliation
Petrini P.-Politecnico di Milano (IT)
6.Saghazadeh S., Rinoldi C., Schot M., Kashaf S.S., Sharifi F., Jalilian E., Nuutila K., Giatsidis G., Mostafalu P., Derakhshandeh H., Yue K., Święszkowski W., Memic A., Tamayol A., Khademhosseini A., Drug delivery systems and materials for wound healing applications, Advanced Drug Delivery Reviews, ISSN: 0169-409X, DOI: 10.1016/j.addr.2018.04.008, Vol.127, pp.138-166, 2018
Abstract:

Chronic, non-healing wounds place a significant burden on patients and healthcare systems, resulting in impaired mobility, limb amputation, or even death. Chronic wounds result from a disruption in the highly orchestrated cascade of events involved in wound closure. Significant advances in our understanding of the pathophysiology of chronic wounds have resulted in the development of drugs designed to target different aspects of the impaired processes. However, the hostility of the wound environment rich in degradative enzymes and its elevated pH, combined with differences in the time scales of different physiological processes involved in tissue regeneration require the use of effective drug delivery systems. In this review, we will first discuss the pathophysiology of chronic wounds and then the materials used for engineering drug delivery systems. Different passive and active drug delivery systems used in wound care will be reviewed. In addition, the architecture of the delivery platform and its ability to modulate drug delivery are discussed. Emerging technologies and the opportunities for engineering more effective wound care devices are also highlighted.

Keywords:

Wound healing, Drug delivery, Transdermal delivery, Microtechnologies, Nanotechnologies

Affiliations:
Saghazadeh S.-Massachusetts Institute of Technology (US)
Rinoldi C.-other affiliation
Schot M.-Massachusetts Institute of Technology (US)
Kashaf S.S.-Massachusetts Institute of Technology (US)
Sharifi F.-Massachusetts Institute of Technology (US)
Jalilian E.-Massachusetts Institute of Technology (US)
Nuutila K.-Brigham and Women's Hospital (US)
Giatsidis G.-Brigham and Women's Hospital (US)
Mostafalu P.-Massachusetts Institute of Technology (US)
Derakhshandeh H.-University of Nebraska (US)
Yue K.-Massachusetts Institute of Technology (US)
Święszkowski W.-other affiliation
Memic A.-King Abdulaziz University (SA)
Tamayol A.-Massachusetts Institute of Technology (US)
Khademhosseini A.-Massachusetts Institute of Technology (US)
7.Chlanda A., Kijeńska E., Rinoldi C., Tarnowski M., Wierzchoń T., Święszkowski W., Structure and physico-mechanical properties of low temperature plasma treated electrospun nanofibrous scaffolds examined with atomic force microscopy, Micron, ISSN: 0968-4328, DOI: 10.1016/j.micron.2018.01.012, Vol.107, pp.79-84, 2018
Abstract:

Electrospun nanofibrous scaffolds are willingly used in tissue engineering applications due to their tunable mechanical, chemical and physical properties. Additionally, their complex openworked architecture is similar to the native extracellular matrix of living tissue. After implantation such scaffolds should provide sufficient mechanical support for cells. Moreover, it is of crucial importance to ensure sterility and hydrophilicity of the scaffold. For this purpose, a low temperature surface plasma treatment can be applied. In this paper, we report physico-mechanical evaluation of stiffness and adhesive properties of electrospun mats after their exposition to low temperature plasma. Complex morphological and mechanical studies performed with an atomic force microscope were followed by scanning electron microscope imaging and a wettability assessment. The results suggest that plasma treatment can be a useful method for the modification of the surface of polymeric scaffolds in a desirable manner. Plasma treatment improves wettability of the polymeric mats without changing their morphology.

Keywords:

Atomic force microscopy, Surface modification, Electrospun fibers, RF plasma treatment, Tissue engineering, Nanomaterial

Affiliations:
Chlanda A.-Warsaw University of Technology (PL)
Kijeńska E.-Warsaw University of Technology (PL)
Rinoldi C.-other affiliation
Tarnowski M.-Warsaw University of Technology (PL)
Wierzchoń T.-Warsaw University of Technology (PL)
Święszkowski W.-other affiliation
8.Rinoldi C., Kijeńska E., Chlanda A., Choińska E., Khenoussi N., Tamayol A., Khademhosseini A., Święszkowski W., Nanobead-on-string composites for tendon tissue engineering, JOURNAL OF MATERIALS CHEMISTRY B , ISSN: 2050-7518, DOI: 10.1039/c8tb00246k, Vol.6, No.19, pp.3116-3127, 2018
Abstract:

Tissue engineering holds great potential in the production of functional substitutes to restore, maintain or improve the functionality in defective or lost tissues. So far, a great variety of techniques and approaches for fabrication of scaffolds have been developed and evaluated, allowing researchers to tailor precisely the morphological, chemical and mechanical features of the final constructs. Electrospinning of biocompatible and biodegradable polymers is a popular method for producing homogeneous nanofibrous structures, which might reproduce the nanosized organization of the tendons. Moreover, composite scaffolds obtained by incorporating nanoparticles within electrospun fibers have been lately explored in order to enhance the properties and the functionalities of the pristine polymeric constructs. The present study is focused on the design and fabrication of biocompatible electrospun nanocomposite fibrous scaffolds for tendon regeneration. A mixture of poly(amide 6) and poly(caprolactone) is electrospun to generate constructs with mechanical properties comparable to that of native tendons. To improve the biological activity of the constructs and modify their topography, wettability, stiffness and degradation rate, we incorporated silica particles into the electrospun substrates. The use of nanosize silica particles enables us to form bead-on-fiber topography, allowing the better exposure of ceramic particles to better profit their beneficial characteristics. In vitro biocompatibility studies using L929 fibroblasts demonstrated that the presence of 20 wt% of silica nanoparticles in the engineered scaffolds enhanced cell spreading and proliferation as well as extracellular matrix deposition. The results reveal that the electrospun nanocomposite scaffold represents an interesting candidate for tendon tissue engineering.

Affiliations:
Rinoldi C.-other affiliation
Kijeńska E.-Warsaw University of Technology (PL)
Chlanda A.-Warsaw University of Technology (PL)
Choińska E.-Warsaw University of Technology (PL)
Khenoussi N.-Université de Haute Alsace (FR)
Tamayol A.-Massachusetts Institute of Technology (US)
Khademhosseini A.-Massachusetts Institute of Technology (US)
Święszkowski W.-other affiliation
9.Nasajpour A., Ansari S., Rinoldi C., Rad A.S., Aghaloo T., Shin S.R., Mishra Y.K., Adelung R., Święszkowski W., Annabi N., Khademhosseini A., Moshaverinia A., Tamayol A., A Multifunctional Polymeric Periodontal Membrane with Osteogenic and Antibacterial Characteristics, Advanced Functional Materials, ISSN: 1616-301X, DOI: 10.1002/adfm.201703437, Vol.28, No.3, pp.1703437-1-8, 2017
Abstract:

Periodontitis is a prevalent chronic, destructive inflammatory disease affecting tooth‐supporting tissues in humans. Guided tissue regeneration strategies are widely utilized for periodontal tissue regeneration generally by using a periodontal membrane. The main role of these membranes is to establish a mechanical barrier that prevents the apical migration of the gingival epithelium and hence allowing the growth of periodontal ligament and bone tissue to selectively repopulate the root surface. Currently available membranes have limited bioactivity and regeneration potential. To address such challenges, an osteoconductive, antibacterial, and flexible poly(caprolactone) (PCL) composite membrane containing zinc oxide (ZnO) nanoparticles is developed. The membranes are fabricated through electrospinning of PCL and ZnO particles. The physical properties, mechanical characteristics, and in vitro degradation of the engineered membrane are studied in detail. Also, the osteoconductivity and antibacterial properties of the developed membrane are analyzed in vitro. Moreover, the functionality of the membrane is evaluated with a rat periodontal defect model. The results confirmed that the engineered membrane exerts both osteoconductive and antibacterial properties, demonstrating its great potential for periodontal tissue engineering.

Keywords:

electrospinning, guided tissue regeneration, osteoconductive, periodontal regeneration, zinc oxide

Affiliations:
Nasajpour A.-Massachusetts Institute of Technology (US)
Ansari S.-University of California (US)
Rinoldi C.-other affiliation
Rad A.S.-Massachusetts Institute of Technology (US)
Aghaloo T.-University of California (US)
Shin S.R.-Massachusetts Institute of Technology (US)
Mishra Y.K.-Kiel University (DE)
Adelung R.-Kiel University (DE)
Święszkowski W.-other affiliation
Annabi N.-Massachusetts Institute of Technology (US)
Khademhosseini A.-Massachusetts Institute of Technology (US)
Moshaverinia A.-University of California (US)
Tamayol A.-Massachusetts Institute of Technology (US)
10.Celikkin N., Rinoldi C., Costantini M., Trombetta M., Rainer A., Święszkowski W., Naturally derived proteins and glycosaminoglycan scaffolds for tissue engineering applications, Materials Science and Engineering C-Materials for Biological Applications, ISSN: 0928-4931, DOI: 10.1016/j.msec.2017.04.016, Vol.78, pp.1277-1299, 2017
Abstract:

Tissue engineering (TE) aims to mimic the complex environment where organogenesis takes place using advanced materials to recapitulate the tissue niche. Cells, three-dimensional scaffolds and signaling factors are the three main and essential components of TE. Over the years, materials and processes have become more and more sophisticated, allowing researchers to precisely tailor the final chemical, mechanical, structural and biological features of the designed scaffolds. In this review, we will pose the attention on two specific classes of naturally derived polymers: fibrous proteins and glycosaminoglycans (GAGs). These materials hold great promise for advances in the field of regenerative medicine as i) they generally undergo a fast remodeling in vivo favoring neovascularization and functional cells organization and ii) they elicit a negligible immune reaction preventing severe inflammatory response, both representing critical requirements for a successful integration of engineered scaffolds with the host tissue. We will discuss the recent achievements attained in the field of regenerative medicine by using proteins and GAGs, their merits and disadvantages and the ongoing challenges to move the current concepts to practical clinical application.

Keywords:

Natural polymers, Hydrogel scaffolds, Glycosaminoglycans (GAGs), Fibrous proteins, Regenerative medicine

Affiliations:
Celikkin N.-Warsaw University of Technology (PL)
Rinoldi C.-other affiliation
Costantini M.-Sapienza University of Rome (IT)
Trombetta M.-Università Campus Bio-Medico di Roma (IT)
Rainer A.-Università Campus Bio-Medico di Roma (IT)
Święszkowski W.-other affiliation

List of chapters in recent monographs
1.
625
Costantini M., Testa S., Rinoldi C., Celikkin N., Idaszek J., Colosi C., Gargioli C., Święszkowski W., Barbetta A., Biomaterials Science Series, Biofabrication and 3D Tissue Modeling, rozdział: 3D Tissue Modelling of Skeletal Muscle Tissue, Royal Society of Chemistry, Edited by Dong-Woo Cho, 3, pp.184-215, 2019

Patents
Filing No./Date
Filing Publication
Autor(s)
Title
Protection Area, Applicant Name
Patent Number
Date of Grant
pdf
435749
2020-10-21
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Pierini F., Nakielski P., Rinoldi C., Pawłowska S., Ding B., Li X., Si Y.
Nanoplatforma dostarczania leków na żądanie, sposób jej wytwarzania oraz zastosowanie
PL, Instytut Podstawowych Problemów Techniki PAN
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