Institute of Fundamental Technological Research
Polish Academy of Sciences

Partners

Ali Khademhosseini

Massachusetts Institute of Technology (US)

Recent publications
1.  Rinoldi C., Kijeńska-Gawrońska E., Heljak M., Jaroszewicz J., Kamiński A., Khademhosseini A., Tamayol A., Swieszkowski W., Mesoporous Particle Embedded Nanofibrous Scaffolds Sustain Biological Factors for Tendon Tissue Engineering, ACS Materials Au, ISSN: 2694-2461, DOI: 10.1021/acsmaterialsau.3c00012, Vol.3, No.6, pp.636-645, 2023
2.  Rinoldi C., Kijeńska-Gawrońska E., Khademhosseini A., Tamayol A., Swieszkowski W., Fibrous systems as potential solutions for tendon and ligament repair, healing, and regeneration, ADVANCED HEALTHCARE MATERIALS, ISSN: 2192-2659, DOI: 10.1002/adhm.202001305, Vol.10, No.7, pp.2001305 - 1-26, 2021
3.  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)
4.  Nasajpour A., Mostafavi A., Chlanda A., Rinoldi C., Sharifi S., Ji M.S., Ye M., Jonas S.J., Święszkowski W., Weiss P.S., Khademhosseini A., Tamayol A., Cholesteryl ester liquid crystal nanofibers for tissue engineering applications, ACS Materials Letters, ISSN: 2639-4979, DOI: 10.1021/acsmaterialslett.0c00224, Vol.2, No.9, pp.1067-1073, 2020

Abstract:
Liquid-crystal-based biomaterials provide promising platforms for the development of dynamic and responsive interfaces for tissue engineering. Cholesteryl ester liquid crystals (CLCs) are particularly well suited for these applications, due to their roles in cellular homeostasis and their intrinsic ability to organize into supramolecular helicoidal structures on the mesoscale. Here, we developed a nonwoven CLC electrospun scaffold by dispersing three cholesteryl ester-based mesogens within polycaprolactone (PCL). We tuned the ratio of our mesogens so that the CLC would be in the mesophase at the cell culture incubator temperature of 37°C. In these scaffolds, the PCL polymer provided an elastic bulk matrix while the homogeneously dispersed CLC established a viscoelastic fluidlike interface. Atomic force microscopy revealed that the 50% (w/v) cholesteryl ester liquid crystal scaffold (CLC-S) exhibited a mesophase with topographic striations typical of liquid crystals. Additionally, the CLC-S favorable wettability and ultrasoft fiber mechanics enhanced cellular attachment and proliferation. Increasing the CLC concentration within the composites enhanced myoblast adhesion strength promoted myofibril formationin vitrowith mouse myoblast cell lines.

Affiliations:
Nasajpour A. - Massachusetts Institute of Technology (US)
Mostafavi A. - other affiliation
Chlanda A. - Warsaw University of Technology (PL)
Rinoldi C. - other affiliation
Sharifi S. - other affiliation
Ji M.S. - other affiliation
Ye M. - other affiliation
Jonas S.J. - other affiliation
Święszkowski W. - other affiliation
Weiss P.S. - other affiliation
Khademhosseini A. - Massachusetts Institute of Technology (US)
Tamayol A. - Massachusetts Institute of Technology (US)
5.  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)
6.  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
7.  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)
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)

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