Biomaterials for Regenerative Medicine: Innovations and Applications

Fundamentals of Biomaterials for Regenerative Medicine


Biomaterials are pivotal in regenerative medicine, facilitating the restoration of tissue function by supporting the integration and growth of new cells. Their selection and application are grounded in biomaterials science and biomedical engineering principles.


Overview of Biomaterials

Biomaterials are materials engineered to interact with biological systems for a medical purpose, be it diagnostic or therapeutic. They encompass a wide range of substances, from metals to polymers and ceramics. In the context of regenerative medicine, these materials are designed to mimic the extracellular matrix, providing a scaffold for tissue formation. A biomaterial scaffold is essential for supporting cellular attachment, proliferation, and differentiation.


Classification and Selection of Biomaterials

Biomaterials are generally classified into four primary types:

  1. Metals: Used for their strength and durability but limited due to potential corrosion.
  2. Ceramics: Biocompatible and often used for bone tissue engineering.
  3. Degradable Polymers: Break down over time making them suitable for temporary scaffolds.
  4. Nondegradable Polymers: Long-lasting and used for permanent implants.
  5. Hydrogels: Highly hydrophilic and can mimic the natural tissue environment.

The selection of a particular biomaterial for regenerative medicine is based on:

  • Biocompatibility
  • Biodegradability
  • Mechanical properties
  • Physical characteristics


Regenerative Medicine: A Primer

Regenerative medicine is an interdisciplinary field that applies the principles of engineering and life sciences toward the repair, replacement, or regeneration of tissues or organs to restore or establish normal function. It relies heavily on the use of biomaterials to create environments conducive to cell growth and differentiation. Regenerative strategies include cell-based therapies, tissue-engineered organs, and the application of biomaterial scaffolds as templates for tissue regeneration.


Design and Fabrication Approaches

The creation of biomaterials for regenerative medicine involves sophisticated techniques to fabricate scaffolds that support tissue development. The methods must ensure biocompatibility and the appropriate microenvironment for cell growth and differentiation.


Scaffold Fabrication Techniques

Scaffold fabrication has to meet specific criteria depending on the application. Bone tissue engineering, for example, often employs scaffolds made of materials such as hydroxyapatite or tricalcium phosphate because of their osteoconductive properties.

  • Electrospinning: used to create nanofibers that mimic the extracellular matrix, suitable for soft tissue engineering.
  • 3D Printing: allows for the precise construction of scaffolds with customized shapes and sizes, beneficial for bone and cartilage tissue engineering.
  • Solvent Casting and Particulate Leaching: often used with alginate or chitosan, providing porous scaffolds that encourage cell migration and nutrient transport.


Advances in Hydrogel Technology

Hydrogels stand out due to their high water content and ability to closely resemble living tissue. They are pivotal in scaffold design for their porosity and soft tissue compatibility.

  • Synthesis: involves cross-linking hydrophilic polymers; often used hydrogels include those based on polyethylene glycol.
  • Tailoring Properties: modifications such as incorporation of bioactive signals can enhance cellular responses. Alginate and hyaluronic acid hydrogels have seen extensive use, particularly for cartilage tissue engineering.


Synthetic and Natural Biomaterials

Synthetic polymers like PLGA (poly(lactic-co-glycolic acid)) and natural biomaterials like collagen and silk biomaterials each have unique advantages in regenerative medicine.

  • Synthetic polymers: provide controlled degradation rates and mechanical strength, with customization possibilities for specific tissue targets.
  • Natural biomaterials: Silk and collagen are widely used for their exceptional mechanical properties and biocompatibility.
  • Functional and Novel Biomaterials: Efforts in synthesis have led to novel biomaterials that can respond to biological stimuli or incorporate inorganic components, including biopolymer-based inorganic biomaterials like bioactive glasses.


Clinical Applications and Challenges

In the arena of regenerative medicine, clinical applications of biomaterials confront various challenges, including ensuring tissue compatibility, optimising mechanical properties, and regulating stem cell fate.


Biomaterials in Tissue Regeneration

The use of biomaterials like decellularized extracellular matrix (ECM) and hyaluronic acid has showcased potential in tissue regeneration applications. Bone repair, for instance, leverages osteoconductive scaffolds to support osteogenic differentiation. Conversely, in nerve regeneration, bioactive scaffolds aim to facilitate directional growth. The efficacy of these materials is afflicted by their mechanical properties and their ability to integrate with host tissue and induce neovascularization.


Stem Cells and Regenerative Medicine

Incorporation of stem cells, including mesenchymal stem cells (MSCs), embryonic stem cells, and induced pluripotent stem cells (iPSCs), into biomaterial constructs offers a powerful avenue for regenerative medicine. These cells can be directed towards specific lineages, such as chondrogenic differentiation for cartilage repair or progenitor cells for cardiac tissue repair. Integrating scaffolds with stem cell sheets has been a novel approach to address complex diseases and trauma.


Biomedical Engineering in Clinical Settings

Biomedical engineering intersects with clinical practice in orthopedics and organ regeneration, among others. For instance, the Mayo Clinic's Biomaterials and Regenerative Medicine Laboratory investigates biomaterials for bone grafts. A significant hurdle is the adaption of drug delivery systems to regulate inflammation and healing, with a current focus on modulating immune responses, such as macrophage behavior, in the regenerative processes.

October 18, 2025
𝗦𝗶𝗺𝗽𝗹𝗲 𝗦𝘂𝗺𝗺𝗮𝗿𝘆: This study explores how we can improve lab-grown liver cells for medical research and drug testing. The MTMLab team works with induced pluripotent stem cells (iPSCs) - special cells that can be transformed into liver-like cells - because real human liver cells are hard to obtain. However, these lab-grown liver cells don't function as well as mature adult liver cells. The research team discovered that the surface environment where these cells grow is crucial for their development. We created tiny fiber scaffolds made from different materials like collagen, decellularized livers, and chitosan that mimic the natural structure around liver cells. When liver cells were grown on these specially designed nanofibers for three weeks, they displayed higher function compared to cells grown on standard surfaces. Our key finding was that both the material composition and the nanoscale fiber structure were important - stiffer synthetic fibers or softer materials without the appropriate topography or composition prevented proper cell maturation. This research helps create better lab models of human liver tissue that can be used for testing new drugs and studying liver diseases more effectively.

2025 BMES Annual Meeting - MTMLab Member Presentations!

October 7, 2025
Owen Lally Modeling the synergistic effects of alcohol and fats on liver disease via engineered cocultures In Vitro Liver Toxicology Testing of Rat and Dog Hepatocytes to Reduce In Vivo Regulatory Requirements Nathan Shelton Enhancing the Functions and Hepatitis B Virus Infectability of Primary Human Hepatocytes Protein Microarrays to Probe Synergistic Effects of Extracellular Matrix Composition and Stiffness on Liver Macrophages Lesly Villarreal Engineering a 3D Placental Trophoblast Invasion Platform Via Droplet Microfluidics Gas-permeable Plates to Model Synergetic Effects of Oxygen and Endothelial Factors on Liver Zonation Emanuele Spanghero Modeling the Interplay Between Liver and Heart Diseases via a Human Dual-Organ Platform Engineering High Cell Density Beating Cords of Cardiomyocytes and Fibroblasts via Photopatterned Alginate

MTMLab Research Summary: Improving Lab-Grown Liver Cell Maturation

May 7, 2025
Our latest study addresses a critical challenge in liver tissue engineering: stem cell-derived liver cells (iHeps) typically remain functionally immature, limiting their usefulness for drug testing and disease modeling. Our research team created 3D microtissues using droplet microfluidics technology by: • Encapsulating iHeps in tiny collagen gel droplets (~250 μm diameter) • Coating these structures with various non-parenchymal cells (NPCs) • Testing different combinations and sequences of supporting cells Key findings: 1) Embryonic fibroblasts and liver sinusoidal endothelial cells (LSECs) produced the most mature iHeps compared to other tested cell types 2) Sequential application of cell signals (embryonic fibroblasts first, then LSECs) yielded optimal maturation 3) Specific growth factors like stromal-derived factor-1 alpha were identified as important maturation enhancers 4) Gene expression analysis confirmed that LSEC/iHep microtissues closely resembled adult human liver cells This platform enables researchers to identify critical cellular interactions and molecular signals that drive liver cell maturation, providing valuable insights for developing more physiologically relevant liver models for drug screening and regenerative medicine applications. https://www.sciencedirect.com/science/article/pii/S174270612500193X SIMPLE SUMMARY: Embryonic fibroblasts and liver sinusoidal endothelial cells dramatically improved iHep maturation compared to other cell types tested, producing more functionally mature liver cells. Sequential application proved crucial—adding embryonic fibroblasts first, followed by endothelial cells, yielded optimal maturation. Specific growth factors including stromal-derived factor-1 enhanced this process. This research enables creation of more authentic mini-liver tissues that function like human liver. These improved models support better drug testing, disease research, and regenerative medicine applications.