Bone Tissue Engineering

BonoFillTM is a tissue-engineered, viable bone graft consisting of the patient’s own mesenchymal cells grown on a natural matrix and has osteogenic, osteoinductive and osteoconductive properties for the optimal promotion of bone regeneration.

Human Adipose Tissue-Derived Mesenchymal Stromal Cells in Bone Tissue Engineering

Adipose (fat) tissue-derived cells are relatively easily retrieved by a simple procedure of liposuction and consists of a heterogeneous population of cells, including mesenchymal stromal cells (MSCs). These potent mesenchymal cells can be cultured and expanded in the laboratory as well as differentiated into mature osteoblasts (bone-forming cells) and chondrocytes (cartilage cells), among others. Moreover, their prevalence in adipose tissue, such as abdominal fat tissue, is relatively high compared to other sources (such as bone-marrow for example) and they can be retrieved by a relatively simple liposuction procedure.

Furthermore, MSCs delivered into an injured or diseased tissue were shown to secrete a variety of factors that enhance the recovery process by recruiting the patient's cells from the surrounding healthy tissue to the injured site and by inducing vascularization, thereby further promoting and enhancing the healing and regeneration process.

When employed to generate autologous (self) grafts, adipose tissue-derived mesenchymal stromal cells provide the advantages of safety, availability and multiple differentiation potential, rendering them a very promising cell source for tissue regeneration, particularly for the repair of skeletal defects.


Tissue Engineering


Scientist around the world are working vigorously on mastering the engineering of a diversity of tissues ex vivo (outside the body) for medical purposes of tissue-regeneration, -reconstruction and -replacement, with the aim to treat illnesses, heal disorders and even replace whole organs.

The two main components of tissue engineering are cells and matrix:

Cells - are the building blocks of tissues, while tissues form the functional units in the body. Cells for tissue engineering are typically grown in vitro (in the laboratory) on a biodegradable and biocompatible carrier (matrix or scaffold).

Matrix - or scaffold, is a carrier designed not only to support cell growth, but also to interact with the surrounding tissue to induce and support the regeneration processes, and can be of a rigid structure or composed of particles of various sizes.

The cells are introduced to the scaffold, and with favorable culture conditions, a tissue will form, capable of restoring, maintaining, or improving damaged tissues or, in the future, even whole organs.

Following transplantation, the cells from within the graft stimulate the natural repair mechanisms in the defective tissue. The goal of tissue engineering is to replace the damaged tissue entirely, and to cure rather than treat complex, often chronic, conditions.

Tissue engineering holds great promise for applications exploiting the patients' own (autologous) cells for the generation of customized, compatible tissues and organs capable of repairing incurable diseases and tissue deficiencies.

Bone Regeneration

Bone tissue engineering represents one of the most challenging, emerging scientific and clinical fields. Although bone tissue naturally regenerates, its self-healing potential is restricted to relatively small fractures. Large bone defects usually require intervention in the form of reconstruction and when caused by trauma, infection or skeletal diseases, bone grafting is necessary to repair or improve the function of injured bone. The optimal healing process of large bone defects requires the combination of the following processes:

  • Osteogenesis: The differentiation of osteoprogenitor cells originating from the transplanted bone graft into bone-forming cells
  • Osteoinduction: The stimulation of osteoprogenitors to differentiate into osteoblasts (bone-forming cells)
  • Osteoconduction: A matrix, or scaffold, acting as a supporting surface for the growth and differentiation of new bone cells
  • Osseointegration: Osseointegration is the stable anchorage of an implant achieved by direct bone-to-implant contact 

Thus, the ideal bone graft substitute should be biocompatible, and possess osteoconductive, osteoinductive and osteogenic properties, as well as have functional and structural similarities to the defective or deficient bone. Furthermore, ideally this bone graft should be easy to handle and preferably also cost-effective.

Current solutions include autologous bone grafts and bone substitutes. Autologous bone grafts - the "gold standard" - a procedure in which a piece of the patient’s healthy bone is retrieved in a surgical procedure and transplanted into the site of the bone defect. Bone substitutes include xenografts – bone grafts from animals, mostly of bovine origin, and synthetic bone substitutes. Nonetheless, these procedures have significant limitations:

  • Autologous transplant: (using own bone) requires secondary surgery for bone harvesting.
    • Invasive surgical procedure
    • Risk of donor site morbidity
    • Frequently insufficient graft volume and quality


  • Bone Substitutes: xenografts or synthetic
    • Inferior bone properties
    • Only relevant for small bone defects
    • Long recovery

Bone tissue engineering presents a promising alternative to autologous bone grafting and possesses the intrinsic properties required for optimal bone healing: osteogenesis, osteoinduction and osteoconduction.

Current obstacles for the engineering of the ideal bone graft:

  • Identification of the ideal cell population to maximize transplantation and regeneration success
  • Inefficient procedures for cell isolation
  • Adequate support of cell expansion on the scaffold
  • Grafting procedure: Bone graft product ease of handling and plasticity to fit a variety of complex deficiencies

To address the limitations of existing bone regeneration therapies, Bonus BioGroup’s developed BonoFillTM bone graft product:

The uniqueness of BonoFillTM is in its smart bone graft design, of biodegradable, mineral scaffold particles covered with a mixture of the patient’s own cells that have both proliferative and osteogenic capabilities. Moreover, BonoFillTM is of semi-solid consistency, and thus injectable, which was found to allow for maximal flexibility, especially with regard to the treatment of complex bone defects.

During the initial phase following transplantation, the bone graft particles enable diffusion of nutrients, and the fact that the bone graft is not a rigid structure likely enables its fast vascularization. Furthermore, mesenchymal stromal cells were found to secrete various factors that enhance and promote the cells’ regenerative properties by recruiting a variety of cells from the surrounding tissue, including the facilitation of vascularization.

The unique cell mixture composing BonoFillTM undergo cell proliferation, osteogenic cell differentiation and maturation in the engrafted defect site, as well as likely recruits the patient’s cells from the surrounding healthy tissue, whilst the mineral scaffold particles serve as ossification seeds that connect together and enhance the bone regeneration process, all of which furthers the full healing of the defect with sturdy, healthy, new bone tissue.

Thus, BonoFillTM offers a novel bone regeneration therapy for a variety of bone deficiencies with an autologous tissue-engineered bone graft designed to precisely fit the patient’s anatomical deficiencies, without running the risk of tissue rejection and surgical failure.



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