Regenerating Poorly Vascularized Tissues

Dear Colleagues,

The goal in regenerative medicine is to repair, replace, or regenerate injured tissues and organs. Through tissue engineering, we attempt to achieve this objective by creating bio-functionalized “constructs” to be used as alternatives to donor material.

Even though advancements in the development of biomaterials and the isolation and culture of competent cells have led to a consistent number of studies applying engineered constructs in various disease models, in many cases, clinical and pre-clinical investigations have shown disappointing outcomes related to efficacy endpoints that have not been met, primarily due to the lack of long-lasting and consolidated defect repairs. One of the most significant factors in these unsatisfactory results could be linked to there being no or inefficient vascularization in the newly formed tissue.

Most tissues in the body are supported by complex blood vessel networks that supply every single cell with essential nutrients and oxygen. The diffusion limit of oxygen has been determined to be 100–200 μm; thus, new blood vessel formation is necessary to support tissue growth beyond this limit. Similarly, tissue-engineered constructs of more than a few hundred microns in thickness have to be vascularized in order to guarantee the success and survival of implants, particularly in cell-based constructs. During in vitro culture, the supply of oxygen and nutrients can be easily achieved using methods such as perfusion bioreactors. However, after implantation, the bio-engineered construct must rely on a perfused vascular network to support the repair and regeneration processes.

To facilitate cell survival in large tissue‐engineered constructs, several strategies have been investigated, primarily focusing on accelerating the angiogenic processes. Angiogenesis is the process of generating new vessels from a pre-existing vascular network surrounding the site of transplantation, but can we also regenerate naturally avascular tissues, such as articular cartilage and tendons? How can we repair injured sites that, due to their pathogenic process, lead to avascular microenvironments (such as non-healing fractures)? In these cases, vasculogenesis, rather than angiogenesis, should be taken into consideration.

Our aim in launching this Special Issue is to explore recent promising research trends in tissue repair and regeneration within microenvironments that have compromised vascular networks, in order to improve the healing process and achieve long-lasting functional recovery. Possible topics for inclusion in this Special Issue include, but are not limited to, the following:

• The development of bioengineered materials;
• The development of pre-vascularized engineered constructs;
• The development of cell-based medicinal products (CBMPs);
• Approaches to treatment and patient management in reconstructive and regenerative medicine;
• Biological aspects of vasculogenesis in adults and its potential applications.

Dr. Simone Pacini
Guest Editor

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• regenerative medicine
• avascular tissue
• angiogenesis
• vasculogenesis
• cell-based medicinal products
• bioengineered materials
• cell transplantation