PARIS – Bellaseno GmbH recently completed a phase I trial of its Senella absorbable soft tissue reconstruction scaffold on an Australian patient with congenital pectus excavatum. “This minimally invasive procedure and fully absorbable scaffold is expected to herald a radical change in soft tissue reconstruction surgery, particularly in breast reconstruction,” Mohit Chhaya, CEO and co-founder of Bellaseno, told BioWorld.
Breast cancer is the most frequent cancer among women with more than 2 million estimated new cases diagnosed worldwide each year, resulting in 522,000 mortalities. There are currently three principal surgery options for breast mound reconstruction following mastectomy or for congenital defects such as pectus excavatum.
However, reconstruction using silicone implants involves several drawbacks, including capsular contracture. Additionally, silicone implants are also subject to potential rupture, displacement, deformation, chronic seroma or hematoma. Free tissue transfer, such as latissimus dorsi, pedicled transverse rectus abdominis myocutaneous, or deep inferior epigastric perforator flap surgery often takes eight to nine hours and is associated with extended in-patient stay and prolonged recovery periods. The main complication with these is that sometimes a clot forms in the vein that drains blood from the flap, or the artery that supplies blood to the flap. Both cases may lead to necrosis of the flap tissue.
Lastly, autologous fat transfer or lipofilling, produces poor clinical results for large volume reconstruction (more than 100 cc), with 40% to 60% reduction in graft volume owing to tissue resorption and necrosis.
Developing an alternative for breast reconstruction
Hence Bellaseno’s proposal to develop a new generation of absorbable material not based on silicone. “This structure will map out the growth of natural tissue,” said Chhaya.
Bellaseno, was formed in 2015 by six co-founders, including Mohit Chhaya, a biomedical engineer and former post-doctorate researcher at the Munich Technical University (TUM); the pioneer of 3D-printed reconstruction scaffolds, Dietmar Hutmacher; Simon Champ, a researcher from BASF; and two plastic surgeons: Severin Wiggenhauser and Thorsten Schantz.
The Leipzig, Germany-based company specializes in the development of new generation implants using additive manufacturing technology. Its ten design engineers have developed a 90%-porous scaffold, made of absorbable polycaprolactone. This exhibits highly specialized topological and design features, and acts as a platform for injected fat tissue harvested using standard liposuction surgery.
Scaffold absorbed within two years
The Senella platform uses absorbable polymer technology that, after implantation, is intended to support regeneration of natural breast tissue. Tissue is regenerated from the patient’s own body fat, without the need for cultivated stem cells or products of animal origin. “The implant is designed to be absorbed over two years, and to provide a stable platform for injected fat tissue to mature, adapt to its environment and stabilize,” said Chhaya. The key patent, covering the design and porosity features of the Senella platform, has just been granted in the U.S. This scaffold platform has been constructed using a bio-compatible and absorbable polymer that is FDA cleared and CE-marked for a variety of other clinical applications.
8 years of developmental preclinical studies
The Senella technology is the result of eight years of developmental preclinical studies. The initial theoretical concept for the Senella technology, using fat injection, was developed jointly in 2012 at the Munich Technical University (Germany) and the Queensland University of Technology (Australia), as part of Chhaya’s thesis under Hutmacher’s supervision. The technology was exclusively licensed by Bellaseno in 2015. Since then, Bellaseno’s engineers have extensively refined the concept to transform it into an actual medical device as part of the Biobreast project funded by the Saxony Development Bank in Germany.
Bellaseno produced five versions of the design between 2017 and 2019, which was finalized in April 2019. Since then, the technology has been validated using more than 50 minipigs, in order to verify that there are no clinical complications down to the technology, as well as no long-term retention of injected fat tissue (more than one year).
Bellaseno’s products are made using additive manufacturing (3D printing). Medical-grade and GMP-certified polymer is sourced directly from the world’s leading suppliers and used directly in the 3D printing process.
The landmark stages in the phase I trial
The phase I trial was carried out by Michael Wagels, staff specialist plastic and reconstructive surgeon at the Princess Alexandra Hospital, and director of the Australian Centre for Complex Integrated Surgical Solutions. “Tissue engineering seemed a logical next step for patients with these particularly complex problems, such as the congenital deformity, pectus excavatum,” Wagels told BioWorld. It is a rare deformation of the thorax, characterized by a median or lateral depression of the sternum. Funnel chest syndrome occurs in 1% to 2% of the population. This is the most common congenital thoracic deformity.
The benefit anticipated from using this absorbable scaffold is its simplicity compared to other orthopedic techniques which use silicone. “The surgery is designed as a minimally invasive procedure, where no bones are touched and recovery is expected to be less painful than other approaches to treatment,” said Wagels. The Australian patient with the pectus excavatum deformity is a 22 year-old female. She was born with a lymphovascular disorder affecting the chest wall and an upper limb, with hypertrophy of the limb. This set of symptoms is known as Klippel-Trenaunay syndrome.
An old 6 cm scar, previously used to insert a tissue expander, was then used to access the anterior aspect of the breast bone. “This necessarily included releasing the sternocostal head of the ipsilateral pectoralis major muscle, as would be routine in breast augmentation surgery,” said Wagels. Once the pocket for the implant had been created, the implant was inserted. Fat graft was then harvested from the patient's thighs and abdomen. The fat was prepared using a standard Coleman fat transfer technique and then injected directly into the implant using a standard fat injection cannula. “An important part of the surgery is injecting the patient’s own fat into the scaffold at the time of implant insertion. This stimulates regeneration of the highly porous scaffold with more than 90% of her own tissue,” said Wagels The wound was then closed in a standard two layer fashion. There was no need for a surgical drain. Light compression dressings were applied as would be routine for breast implant surgery.
Follow-up imaging of the patient and her implant is scheduled for eight weeks following surgery. Primary endpoint of the trial will be assessment of post-operative adverse device effects (ADE) 12 and 24 months after scaffold implantation. Secondary endpoints cover safety criteria such as adverse events, frequency of complications (short term and long term), amount of revision surgery due to ADEs, and pain.
In addition to congenital deformities such as pectus excavatum, the Bellasenos team will carry out feasibility studies on corrective breast augmentation and corrective breast reconstruction patients as the immediate next steps. “This involves patients who have previously had silicone implants, but now need to replace them because of complications such as capsular contracture, a breast-implant illness,” said Chhaya. Following the feasibility studies, Bellaseno will perform a pivotal trial on a large number of subjects, before seeking regulatory approval in 2023.
The company is targeting the $1.8 billion breast reconstruction market, currently showing a CAGR of 5.5%, according to Grandview Research Inc.
“Corrective reconstruction is also a rapidly growing market segment, which will be a target market for Bellaseno,” said Chhaya. In such cases, patients have already had silicone breast implants, but need to replace them because of complications such as capsular contracture. In fact, all silicone implant manufacturers now specify that silicone implants are not lifetime devices, so a very large number of patients who currently have silicone implants will need up to three revision procedures at some point in their lives.
Bellaseno faces three main competitors in this market: U.S.-based Mentor Corp, a subsidiary of Johnson & Johnson; Allergan Aesthetics, an Abbvie company; and Costa Rica-based Establishment Labs Holdings Inc.
“We have three major competitive advantages: no permanent implant due to regeneration of own tissue, the potentially fewer health complications because of safer and well-characterized materials, and lastly, the potential for highly patient-specific outcomes,” said Chhaya.
The company believes its versatile soft tissue regeneration platform can be used in a wide range of reconstruction applications. The flagship application is breast reconstruction, but it could also potentially be extended to orthopedic soft tissue repairs. A market equally worth $1.8 billion, and growing at an attractive CAGR of more than 7.5%, according Grandview.
Since its formation, Bellaseno has raised more than $7 million from a combination of private equity, one of Germany’s top bio-entrepreneurs, and government grants from the Saxony Development Bank and the European Fund for Regional Development. “Once we obtain successful results from phase I and clinical feasibility trials, we are planning a series C round of $24 million to $42 million in early to mid-2021, to carry out pivotal phase III trials, needed for regulatory approval,” said Chhaya.