About

Riccardo Gottardi, PhD, is an Assistant Professor of Pediatrics specializing in Pulmonary Medicine at the University of Pennsylvania. He serves as Chief Scientist of the Pediatric Airway Frontier Program at the Children’s Hospital of Philadelphia. Dr. Gottardi is a member of the Center for Musculoskeletal Disorders and the Institute for Regenerative Medicine at the University of Pennsylvania. His research focuses on biofabrication, cartilage regeneration, and the development of in vitro models for studying tissue repair and inflammatory responses. He has contributed to advancing understanding in vocal fold scarring, osteochondral micro-physiological systems, and bioengineering scaffolds for cartilage and trachea regeneration. Dr. Gottardi's work integrates biomedical engineering, molecular biology, and regenerative medicine to develop innovative therapeutic strategies.

Research topics

• Materials science
• Biochemistry
• Chemistry
• Biomedical engineering
• Medicine

Selected publications

• A Novel Decellularized Fibrocartilage Graft Promotes Tympanic Membrane Repair

  Advanced Healthcare Materials · 2026-05-02

  articleOpen accessSenior author

  Tympanoplasty repairs tympanic membrane (TM) perforations using grafts. In pediatric patients, cartilage grafts are preferred over fascia due to superior mechanical properties that prevent complications from negative middle ear pressure, including graft failure, retraction, and cholesteatoma formation. However, autologous grafts cause donor-site morbidity and increased surgical time. To overcome these limitations, we engineered an allogeneic porcine meniscus decellularized (MEND) fibrocartilage graft with a unique microchannel structure created by selective elastin and vascular digestion to promote host cell invasion and integration. We evaluated MEND in a rat TM acute perforation model, comparing outcomes to autologous cartilage and fascia grafts, the current clinical standards of care. TMs were monitored via otoendoscopy through 4 weeks, then analyzed by histology and immunohistochemistry. MEND and auricular cartilage grafts successfully closed perforations by day 3, outperforming fascia grafts which frequently dislodged due to poor mechanical integrity. However, unlike cartilage grafts, MEND fully remodeled by day 28, providing superior graft closure and tissue integration compared to both traditional materials. These findings demonstrate MEND's potential as an off-the-shelf solution for pediatric tympanoplasty.

  PublisherDOI

• DECELLULARIZED MENISCUS (MEND) AS A BIOMATERIAL THAT SUPPORTS STEM CELL INVASION AND CHONDROGENESIS

  Orthopaedic Proceedings · 2025-09-29

  articleSenior author

  Cartilage damage affects 25 million people annually due to trauma, sports injuries, and wear and tear. Mesenchymal stem cells (MSCs) are commonly used for tissue-engineered cartilage repair due to their accessibility and proliferation capacity compared to chondrocytes. However, MSC-based approaches often result in non-uniform matrix secretion and limited chondrogenesis in 3D hydrogels. Incorporating cartilage-derived extracellular matrix (ECM) into constructs can enhance chondrogenesis. Building on this concept, the Gottardi lab developed a novel scaffold made from decellularized porcine meniscus (MEND). MEND retains mechanical properties suitable for cartilage repair, offers high porosity for cell infiltration, and is generated via selective elastin removal. This study investigates whether MEND supports MSC recellularization and possesses intrinsic pro-chondrogenic potential. MEND is compared to traditional hydrogels, such as methacrylated type I collagen (ColMA) and gelatin-hyaluronic acid (GelMA/HAMA). MEND Fabrication : Porcine meniscus sections were enzymatically processed to remove elastin while preserving mechanical integrity. Cylinders were punched from the red zone region, pre-soaked in serum-containing medium, and seeded with MSCs at varying densities. Hydrogel Constructs and Controls : MSCs were cultured in ColMA and GelMA/HAMA hydrogels or as pellets for positive controls. All constructs were cultured in chondrogenic medium for 21 days. Analysis : Chondrogenesis was assessed via histology, immunofluorescence, RT-qPCR, and biochemistry, focusing on GAG and collagen production. Hydrogels : ColMA and GelMA/HAMA constructs exhibited non-uniform matrix secretion after 21 days, with sporadic GAG and collagen expression in ColMA and variability in GelMA/HAMA, as well as substantive contraction of ColMA hydrogels. MEND : Structural analyses confirmed elastin removal, decellularization, porosity (8%), and channels diameters averaging 8µm. MSCs successfully seeded into MEND with uniform distribution and viability. MEND's porosity enables effective MSC infiltration and distribution, addressing limitations of existing hydrogels. Initial chondrogenesis in pellets and hydrogels showed dis-homogeneous matrix secretion. We observed good differentiation in all conditions and used non-canonical amino acids to directly tag newly synthetized matrix. MEND's ECM composition, including collagen I, II, and hyaluronic acid, provides a cartilage-like environment conducive to chondrogenesis, albeit not chondrogenic in and of itself. Without any contraction, MEND offers a promising scaffold for articular cartilage engineering due to its cartilage-like composition, mechanical properties, and capacity for MSC repopulation.

  PublisherDOI

• CYR61 delivery promotes angiogenesis during bone fracture repair

  npj Regenerative Medicine · 2025-04-22 · 10 citations

  articleOpen access

  Compromised vascular supply and insufficient neovascularization impede bone repair, increasing risk of non-union. CYR61, Cysteine-rich angiogenic inducer of 61kD (also known as CCN1), is a matricellular growth factor that has been implicated in fracture repair. Here, we map the distribution of endogenous CYR61 during bone repair and evaluate the effects of recombinant CYR61 delivery on vascularized bone regeneration. In vitro, CYR61 treatment did not alter chondrogenesis or osteogenic gene expression, but significantly enhanced angiogenesis. In a mouse femoral fracture model, CYR61 delivery did not alter cartilage or bone formation, but accelerated neovascularization during fracture repair. Early initiation of ambulatory mechanical loading disrupted CYR61-induced neovascularization. Together, these data indicate that CYR61 delivery can enhance angiogenesis during bone repair, particularly for fractures with stable fixation, and may have therapeutic potential for fractures with limited blood vessel supply.

  PublisherOA PDFDOI

• Controlled decorin delivery from injectable microgels promotes scarless vocal fold repair

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-06-28 · 1 citations

  preprintOpen accessSenior authorCorresponding

  Vocal fold (VF) scarring is a leading cause of poor voice, yet no therapies exist to prevent its progression. Current treatments, such as intracordal steroid injections, offer limited efficacy and carry significant off-target toxicities. To identify targeted anti-scarring strategies, we performed transcriptomics of human VF myofibroblasts, the cellular drivers of VF scarring, and identified the proteoglycan decorin (DCN) as downregulated in activated myofibroblasts. We also show a time-dependent decrease in DCN during fibrotic wound healing in a preclinical rat model of VF scarring. Administration of DCN suppressed VF myofibroblast activation by reducing pro-fibrotic gene expression, α-smooth muscle actin (α-SMA) levels, and cell contractility. DCN was encapsulated in hyaluronic acid microgels for sustained protein release for 3-4 weeks. In a rat model of VF scarring, DCN-loaded microgels prevented hallmark features of scarring, including collagen deposition and myofibroblast activation. These findings highlight DCN as a promising therapeutic and provide a sustained delivery platform with translational potential against VF scarring.

  PublisherOA PDFDOI

• DEVELOPING AN IN VITRO OSTEOCHONDRAL MICRO-PHYSIOLOGICAL SYSTEM FOR MODELLING CARTILAGE-BONE CROSSTALK IN ARTHRITIS

  Osteoarthritis and Cartilage · 2025-04-01 · 1 citations

  articleSenior author
  PublisherDOI

• Biofabrication of an <i>in situ</i> hypoxia-delivery scaffold for cartilage regeneration

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-03-10

  preprintOpen accessSenior author

  ABSTRACT Osteoarthritis (OA) is a debilitating joint condition affecting millions of people worldwide, triggering painful chondral defects (CDs) that ultimately compromise the overarching patients’ quality of life. Currently, several reconstructive cartilage techniques (RCTs) (i.e.: Matrix-assisted Autologous Chondrocytes Implantation - MACI) has been developed to overcome the total joint replacement (TJR) limitations in the treatment of CDs. However, there is no consensus on the effectiveness of RCTs in the long term, as they do not provide adequate pro-regenerative stimuli to ensure complete CDs healing. In this study, we describe the biofabrication of an innovative scaffold capable to promote the CDs healing by delivering pro-regenerative hypoxic cues at the cellular/tissue level, to be used during RCTs. The scaffold is composed of a gelatin methacrylate (GelMA) matrix doped with hypoxic seeds of GelMA functionalized with a fluorinated oxadiazole (GelOXA), which ensures the delivery of hypoxic cues to human articular chondrocytes (hACs) embedded within the scaffold. We found that the GelMA/GelOXA scaffold preserved hACs viability, maintained their native phenotype, and significantly improved the production of type II collagen. Besides, we observed a reduction in type I and type X collagen, characteristic of unhealthy cartilage. These findings pave the way for the regeneration of healthy, hyaline-like cartilage, by delivering hypoxic cues even under normoxic conditions. Furthermore, the GelMA/GelOXA scaffold’s ability to deliver healing signals directly to the injury site holds great potential for treating OA and related CDs, and has the potential to revolutionize the field of cartilage repair and regenerative medicine.

  PublisherOA PDFDOI

• Decellularized Meniscus (MEND) as a biomaterial that supports stem cell invasion and chondrogenesis

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-10-17

  preprintOpen accessSenior authorCorresponding

  BACKGROUND: Cartilage damage affects 25 million people globally each year. Tissue engineering strategies such as microfracture and matrix induced autologous chondrocyte implantation (MACI) are currently being used in the clinic; however, they are accompanied by their own limitations such as donor site morbidity, rapid clearance from the injury site, and extensive cost. To overcome these limitations, the tissue engineering field has shown increasing interest in the use of decellularized extracellular matrix (dECM) biomaterials due to their heightened integration with native tissue and regeneration rates. METHODS: The Gottardi Lab has developed a new dECM material sourced from porcine men iscus d ecellularization (MEND), in which elastin fibers are removed via enzymatic digestion, resulting in channels that can be easily recellularized. RESULTS: In this work we demonstrate that MEND can be seeded with bone-marrow derived mesenchymal stem cells (MSCs), achieving a uniform distribution of cell nuclei throughout the cross section of the scaffold. We also show that MEND retains its native structure in the presence of MSCs and can support chondrogenesis comparably to other commonly used tissue engineering materials such as methacrylated type I collagen and gelatin/hyaluronic acid hydrogels. CONCLUSION: Overall, MEND is a promising new dECM biomaterial for cartilage regeneration.

  PublisherOA PDFDOI

• 4D Bioprinted Self‐Folding Scaffolds Enhance Cartilage Formation in the Engineering of Trachea (Adv. Mater. Technol. 6/2025)

  Advanced Materials Technologies · 2025-03-01

  articleOpen access

  4D Bioprinted Self-Folding Scaffolds In article number 2401210, Riccardo Gottardi, Carmelo DeMaria, and co-workers present the fabrication via extrusion bioprinting of a bilayer scaffold programmed to self-fold after the printing to mimic the human tracheal anatomy. The scaffold is populated by human cells and supports the maturation of healthy cartilage in its outer part. The design of the scaffold was guided by mathematical modeling.

  PublisherOA PDFDOI

• Effects of Donor Age and Sex on Stemness Marker Expression of Periosteum-derived Progenitor Cells (PPCs)

  Scholarly Commons (University of Pennsylvania) · 2025-09-15

  otherOpen accessSenior author

  Bone regeneration is a rapidly expanding field. Due to this, demand for characterization of bone-like stem cells has been on the rise. This poster presents a project on the effects of sex and age on the stemness of Periosteum-derived Progenitor Cells (PPCs). It was hypothesized that donor age and sex played a role in the stemness of PPCs. To test the hypothesis, it was planned to compare the expression of stem marker genes in patients of different age and sex. Two categories for age were made: young (0-8 years old) and old (14-18 years old) donors. After extracting the cells from donor tissue, RT-PCR was used to measure the expression of stem marker genes. Basic tests were also done using flow cytometry to test its effectiveness in characterization of PPCs. As of now, this investigation showed that there is no statistical difference between samples of different ages, so age does not appear to affect PPC stemness. There were also not enough female samples to run experiments based on sex. However, flow cytometry was proven to be effective in characterizing PPCs. Therefore, the future directions of this project involve characterizing a larger sample of donors with both flow cytometry and RT-PCR to ensure age does not play a role in PPC stemness, while exploring the role of sex in PPC stemness.

  Publisher

• Biofabrication of an <i>in situ</i> hypoxia-delivery scaffold for cartilage regeneration

  Biofabrication · 2025-03-06 · 4 citations

  articleOpen accessSenior author

  Osteoarthritis (OA) is a debilitating joint condition affecting millions of people worldwide, triggering painful chondral defects (CDs) that ultimately compromise the overarching patients' quality of life. Currently, several reconstructive cartilage techniques (RCTs) (i.e.: matrix-assisted autologous chondrocytes implantation has been developed to overcome the total joint replacement limitations in the treatment of CDs. However, there is no consensus on the effectiveness of RCTs in the long term, as they do not provide adequate pro-regenerative stimuli to ensure complete CDs healing. In this study, we describe the biofabrication of an innovative scaffold capable to promote the CDs healing by delivering pro-regenerative hypoxic cues at the cellular/tissue level, to be used during RCTs. The scaffold is composed of a gelatin methacrylate (GelMA) matrix doped with hypoxic seeds of GelMA functionalized with a fluorinated oxadiazole (GelOXA), which ensures the delivery of hypoxic cues to human articular chondrocytes (hACs) embedded within the scaffold. We found that the GelMA/GelOXA scaffold preserved hACs viability, maintained their native phenotype, and significantly improved the production of type II collagen. Besides, we observed a reduction in type I and type X collagen, characteristic of unhealthy cartilage. These findings pave the way for the regeneration of healthy, hyaline-like cartilage, by delivering hypoxic cues even under normoxic conditions. Furthermore, the GelMA/GelOXA scaffold's ability to deliver healing signals directly to the injury site holds great potential for treating OA and related CDs, and has the potential to revolutionize the field of cartilage repair and regenerative medicine.

  PublisherDOI

Frequent coauthors

• Rocky S. Tuan

  Chinese University of Hong Kong

  86 shared

• Irene Chiesa

  Piaggio (Italy)

  62 shared

• Roberto Di Gesù

  University of Bologna

  60 shared

• Matthew R. Aronson

  University of Pennsylvania

  35 shared

• Ian N. Jacobs

  Children's Hospital of Philadelphia

  34 shared

• Giovanni Vozzi

  University of Pisa

  26 shared

• Peter G. Alexander

  University of Pittsburgh

  26 shared

• Steven R. Little

  McGowan Institute for Regenerative Medicine

  26 shared

Labs

• Pediatric Pulmonary Research LabPI

Education

• B.S., General Physics

  University of Pisa, Italy

  2003

• M.S., Applied Physics, Medical Physics

  University of Pisa, Italy

  2003

• Ph.D., Inform., Communication Sci. & Tech. & Electronics & Inform. Engineering, Biomedical Engineering

  University of Genova, Italy

  2007