Published evidences

Preclinical publications

The HYALOFAST® surgical procedure was developed based on in-vitro and in-vivo preclinical evidence, demonstrating the role of the HYAFF® scaffold on MSCs.
These studies have been carried out in internationally well-recognized laboratories throughout the world, such as:

  • Case Western Reserve University, Cleveland, USA – Skeletal Research Centre – Department of Biology
  • Rizzoli Orthopaedic Institute, Bologne, Italy
  • University of Padova, Italy – Department of Histology, Microbiology and Biomedical Technology

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Authors: Ashley Titan, M.D., Michael Schär, M.D., Ian Hutchinson, M.D., Marco
Demange, M.D., Tony Chen, Ph.D., and Scott Rodeo, M.D.
Bibl. Ref.: THE JOURNAL OF ARTHROSCOPIC AND RELATED SURGERY; May 2020; (36):1431-1440
Summary: An in vitro experiment was conducted to determine whether (1) leukocyte-rich human –
platelet-rich plasma (L-PRP) or (2) leukocyte-rich platelet-rich fibrin (L-PRF) delivered on Hyalofast
at a bovine chondral defect, were able to improve tissue formation when compared to Hyalofast
alone. The analysis was based on biomechanical, histologic, and biochemical measures at 28 and
42 days’ time points. It was found that L-PRF elicited the greatest degree of cellularity, collagen
production, whereas L-PRP facilitated the greatest amount of sGAG production. There was no
superiority observed in biomechanical strength between the platelet concentrates used. Delivery
of leukocyte-rich platelet concentrates in conjunction with a HA scaffold may allow for
improvements in cartilage healing through different pathways. – View Abstract

Authors: Lisignoli G., Cristino S., Piacentini A., Toneguzzi S., Grassi F., Cavallo C., Zini N., Solimando L., Maraldi N.M., Facchini A.
Bibl. Ref.: BIOMATERIALS 2005;(26):5677-5686
Summary: MSCs were analyzed on Hyalofast® to obtain new information on the sequence of cellular and molecular events during in vitro chondrogenic differentiation. MSCs chondrogenesis on Hyalofast® is well induced by TGFb1 (a polypeptide member of the transforming growth factor beta superfamily of cytokines whose chondroinductive effects have been well established in MSCs) favoring the in vitro formation of a cartilage like construct. Hyalofast® favors the chondrogenic differentiation of MSCs, allowing them to express typical chondrogenic markers of such as collagen type II, IX, aggrecan and Sox-9 mRNAs. At the same time the expression of collagen type I is down-regulated, as observed in physiological hyaline cartilage. It has to be noted that protein expression of collagen type II is observed already on day 14 in a few areas and on day 28 in the entire scaffold, suggesting that MSC differentiation is very fast.
Credit line: PubMed – View abstract

Authors: Lisignoli G., Cristino S., Piacentini A., Cavallo C., Caplan A.I., Facchini A.
Bibl. Ref.: JOURNAL OF CELLULAR PHYSIOLOGY 207: 364-373 (2006)
Summary: The interaction between human mesenchymal stem cells and Hyalofast® has been analyzed in vitro demonstrating a specific informative role of Hyalofast® in the modulation of inflammatory and degenerative factors. A direct action of Hyalofast® has been demonstrated on hMSCs in modulating the expression and release of both CXC chemokine receptors such as CXCL12 (SDF1)/CXCR4, CXCL13/CXCR5 and catabolic/inhibiting factors as MMP3, MMP13 and TIMP1. These data suggest that the use of Hyalofast® in tissue repair might favour the engraftment of specific precursor cells in the damaged area by the regulation of biological signaling.
Credit line: PubMed – View abstract

Authors: Zavan B., Giorgi C., Bagnara G.P. Vindigni V., Abatangelo G., Cortivo R.
Bibl. Ref.: EUROPEAN JOURNAL OF HYSTOCHEMISTRY 2007; vol. 51 supplement 1:1-8
Summary: Hyalofast® was used for in vitro commitment of bone marrow mesenchymal stem cells (MSC). Cells were cultured either in monolayer and in 3D conditions up to 35 days. In order to monitor the differentiating processes molecular biology and morphological studies were performed at different time points. MSCs grown onto Hyalofast® were able to acquire a unique phenotype of chondrocytes and osteocytes depending on the presence of specific differentiation inducing factors added into the culture medium. Hyalofast® permitted differentiation of MSCs to osteogenic and chondrogenic phenotype in the presence of appropriate stimuli.
Credit line: PubMed – View abstract

Authors: Grigolo B., Lisignoli G., Desando G., Cavallo C., Marconi E., Toschon M., Giavaresi G., Fini M., Giardino R., Facchini A.
Bibl. Ref.: TISSUE ENG PART C Volume 15, Number 4, 2009 (647-658)
Summary: An in vivo experiment in a rabbit osteoarthritis model was performed. The surgical osteoarthritis model was based on anterior cruciate ligament transaction (ACLT). Upon surgery animals were divided into 4 groups: sham operated, ACLT, ACLT – Hyalofast® only and ACLT- Hyalofast® with MSCs. After 3 and 6 months, histomorphometrical and immunohistological evaluations were performed. Data showed that MSCs seeded on Hyalofast® can positively interfere with osteoarthritis progression. It has to be noted that, in this model, in the scaffold only group there is no access to the subchondral bone, therefore no MSC population could come in contact with the lesion area. Results show statistically significant influence of the MSC-loaded Hyalofast® on disease progression by the formation of cartilaginous tissue at the site of the lesion.
Credit line: PubMed – View abstract

Authors: Lisignoli G., Cristino S, Piacentini A, Zini N, Noël D, Jorgensen C, Facchini A.
Bibl. Ref.: J BIOMED MATER RES A. 2006 Jun 1;77(3):497-506
Summary: Cellular morphology, proliferation, and chondrogenic/osteogenic gene expression of mesenchymal stem cells in Hyalofast® were analyzed at different time points. Primary h-MSCs grown onto Hyalofast® in presence of appropriate stimuli formed a cartilage-like structure. Collagen type II and aggrecan increase during the chondrogenic differentiation. At the protein level, collagen type II was uniformly expressed.
Credit line: PubMed – View abstract

Authors: Facchini A., Lisignoli G., Cristino S., Roseti L., De Franceschi L., Marconi E., Grigolo B.
Bibl. Ref.: Biorheology 2006; 43 (3-4): 471-80
Summary: The behavior of mesenchymal stem cells grown on Hyalofast® was analyzed at different time points by Real-Time RT-PCR and immunohistochemical analyses. The data obtained showed that Hyalofast® is able to provide a good environment to support the differentiation of mesenchymal stem cells in chondrogenic sense. These observations confirm Hyalofast® as a suitable scaffold for mesenchymal stem cells for the treatment of articular cartilage defects.
Credit line: PubMed – View abstract

Authors: Cavallo C., Desando G., Columbaro M., Ferrari A., Zini N., Facchini A., Grigolo B.
Bibl. Ref.: J Biomed Mater Res A. 2012 Nov. 7
Summary: The aim of this study was to investigate the phenotype of cells from bone marrow concentrate (BMC) and their ability to differentiate into chondrogenic lineage once seeded onto Hyalofast®. The chondrogenic potential of BMC has been evaluated by means of morphological, histological, immunohistochemical and molecular analyses. The data obtained demonstrated that cells from bone marrow concentrate grown onto Hyalofast® are able to differentiate into chondrogenic sense by the expression and production of specific extracellular molecules. These findings support the use of Hyalofast® and bone marrow concentrate for the repair of cartilage lesions in a ‘‘One Step’’ procedure.
Credit line: PubMed – View abstract