Functional Bio-based Materials for Regenerative Medicine: From Bench to Bedside (Part 2)

Polymer-based biomaterials are a material of choice for many surgeons due to their availability and durability. Many types are available on the market, but the search for improved properties to cater to technology demands, such as 3D printing, continues. Polyamide, to be used as an alternative in craniofacial reconstruction, has been a subject of interest recently. This chapter explores the physical and mechanical properties of polyamide composites fabricated viainjection moulding and 3D printing techniques along with their biocompatibility. With promising physical, mechanical, and biocompatibility properties, polyamide composites are expected to emerge as an alternative biomaterial for craniofacial reconstruction soon.

Polymer-based biomaterials are a material of choice for many surgeons due to their availability and durability. Many types are available on the market, but the search for improved properties and to cater to technology demands, such as 3D Printing, continues. Polyamide, used as an alternative in craniofacial reconstruction, has become a subject of interest recently. This chapter explores the physical and mechanical properties of polyamide composites fabricated via injection moulding and 3D printing techniques, along with their biocompatibility. With promising physical, mechanical, and biocompatibility properties, polyamide composites are expected to emerge as an alternative biomaterial for craniofacial reconstruction soon.

Tendon and ligament injuries are very common and affect many people worldwide. Tendon and ligament injuries may cause serious morbidity to the patients as these tissues play a very important role in body mobility. Cell sheet technology is one of the new tissue engineering approaches introduced to promote tendon and ligament repair. Cell sheets for tendon and ligament repair are commonly prepared using mesenchymal stem cells and tendon/ligament-derived stem cells. Due to their poor mechanical properties, cell sheets are used to wrap around the ligated tendon/ligament, the graft, and the engineered tendon/ligament to hasten tissue regeneration. To date, the application of cell sheet technology in tendon and ligament repair is still at an early stage. However, results from the preclinical studies are promising. Generally, cell sheets were found to hasten tendon and ligament healing, promote graft integration at the tendon-bone interface, and improve the mechanical strength of the healed tissues. More studies, especially the randomised clinical trials, are needed in the future to validate the efficacy of cell sheets in tendon and ligament repair.

Recently, cellulose nanocrystals (CNC) have gained attention from researchers around the world due to their favourable properties such as low cost, nontoxicity, biodegradability, biocompatibility, and as small, strong hydrophilic materials, which render them favourable candidates for the preparation of hydrogels. The incorporation of CNC within a hydrogel matrix enables the hydrogel to sustain its shape during swelling-deswelling. Besides absorbing and retaining large amounts of water, hydrogels also respond to specific external environmental factors, such as temperature, pH, the presence of ions, and concentration, making them appealing to be engineered for drug delivery applications. In addition, CNCs also confer high mechanical strength and thermal stability to the hydrogels, which expand their potential in biomedical applications. This chapter focuses on the synthesis of nano cellulosebased hydrogels for drug delivery applications, including the extraction of CNC from various sources, fabrication of hydrogels using chemical and radiation crosslinking, the chemical, physical, and ‘smart’ properties of the hydrogels, and their application in controlled drug delivery.

Electrospinning is a commonly used approach to fabricate nanofibers of various morphologies. This method is highly effective and economically feasible, capable of producing flexible and scalable nanofibers from a wide variety of raw materials. To construct an ideal nanofiber with the desired morphological properties, electrospinning parameters involving the process, solution, and ambiance need to be fulfilled. Electrospun natural and synthetic polymeric nanofibers have recently proved to be a promising technique for drug delivery systems. Nanofiber-based drug delivery mechanisms can be utilised to transport drugs to specific locations and for a period of time to obtain the intended therapeutic outcomes. The use of electrospun nanofibers as drug carriers in biomedical applications, particularly in transdermal drug delivery systems, may be impressive in the future. Generally, in this kind of system, the active agent or drugs are delivered through the skin into the systemic circulation through a transdermal drug delivery mechanism that is distributed through the skin’s surface. Therefore, by using electrospun nanofibers as the carrier of drugs for transdermal delivery, the system can enhance the drug’s bioavailability and achieve controlled release.

Damage to different body tissues may occur as a result of trauma, injury, or disease, which requires therapies to aid their healing through repair or regeneration. Tissue engineering aims to repair, sustain or recover the function of injured tissue or organs by producing biological substitutes. Advances in different approaches of dental tissue engineering, ranging from conventional triad (stem cells, scaffold, and regulatory signals-based tissue engineering) to modern technologies (3D printing and 4D printing), further emphasize that there are promising treatment approaches offered by the dental tissue engineering field to a variety of orofacial disorders, specifically through the design and manufacture of materials, application of appropriate regulatory signals and the enhanced knowledge of stem cells application. Inspired by their unique properties, scaffolds of natural origins, such as chitosan, cellulose, alginate, collagen, silk, and gelatin, have become a popular source of materials manufacturing that would simulate the biological environment. Future research should focus on translating laboratory findings into feasible therapies, i.e., directing basic sciences discovered in dental tissue engineering into contemporary clinically applicable therapies for orofacial disorders.

Scaffolds represent one of the key components in the tissue engineering triad. Construction of a vascular graft begins with the scaffold that acts as the base building material. Whether natural or synthetic, selecting the right scaffold material is essential to ensure the structural integrity of a graft. The structural integrity could further be strengthened with the addition of cells and regulatory signals that make up the whole tissue engineering triad. In this chapter, a selection of scaffold materials is discussed, and cell seeding strategies are later elaborated, covering the principle of the tissue engineering triad in vascular research.

Periodontitis draws much attention because of its escalating burden on the healthcare economy in both developed and developing countries. For decades, periodontitis has been acknowledged as the most common oral disease worldwide and mostly found in the productive age. The inflammation in periodontal tissue destructs periodontal complex structures: periodontal ligament, cementum, and alveolar bone. Hence, its therapy is directed to interrupt disease progression and restore damaged tissue. The regenerative approach has been recognized by the periodontal association, and it has been integrated in their clinical practice guidelines for treating periodontitis. Various regenerative therapies have been introduced to dental clinics, which provide a wide range of treatment services. The regenerative approach is selected based on the consideration involving the interest of patients and clinicians. However, in its development, regulatory, public, and manufacturer concerns must also be taken into account. This paper exclusively discusses bio-functional materials used in dental clinics to regenerate periodontal defects. The brief evaluation describes recent periodontal regenerative materials available in clinics and clinician’s expectations of future therapies. 

There is an inadequate supply of tissues and organs for transplantation due to limitations in organ donors and challenges surrounding the use of autografts. The search for biodegradable and compatible tissue constructs as a platform for cellular, gene, and immune therapies, as well as drug deliveries, warrant intensive investigations. Biologically compatible materials with unique properties are needed as substrates or scaffolds for many types of cellular and gene therapies, which include treatment for ocular surface regeneration. Although the cornea is one of the most successful organ transplantations because it is considered an immune-privileged site, there are limitations like the risk of graft rejection, the transmission of diseases, and the scarcity of donors. Based on a clear understanding of the anatomy and physiology of the cornea, types of biomaterials, fabrication, and adjunct use of biologics are among the regenerative strategies employed in the tissue engineering approach for corneal regeneration. This chapter highlights the indications for cornea replacement, common biomaterials, and biologics used in this field.

Bones are the hardest tissue in the human body, but they may also sustain injuries when stressed. The most common injury that can occur to bone is fractures. Bones are unique in that they can heal themselves. However, failure of healing may occur if the bone defect is large. The healing process that occurred may not be perfect; nonunion and scar formation may occur, which eventually impair the function of the bone. The elderly is prone to the incidence of falling, which may cause bone fractures. This age group of individuals, especially women who are experiencing menopause, will face delays in fracture healing. This will ultimately affect the quality of life of these individuals. This situation has led researchers to venture into bone engineering or bone regeneration in order to facilitate bone healing and induce new bone formation which can restore bone function. Bone regeneration involves the usage of the bone scaffold as a starting point for new bone formation. The scaffolds must have specific characteristics to allow new bone growth without causing adverse effects on the surrounding tissue. This chapter discusses the biomaterials that can be used in developing scaffolds for use in bone regeneration. Their characteristics (advantages and disadvantages) and modifications of the scaffold to enhance their performance are also highlighted. Their usage as a drug delivery system is also described.

Delayed fracture healing and non-union fractures are major orthopaedic issues that have become a significant healthcare burden. Among many approaches, bone grafts facilitate the healing of non-union fractures. Native cancellous bones represent a more viable and advantageous source of bone grafts due to structural and biochemical similarity with natural bone. They also provide a large surface-to-volume ratio to host cells and for the formation of the vasculature. Given these advantages, we aimed to review some of the recent innovations in native cancellous bone graft production, such as bone selection, decellularisation, demineralisation, and in vitro and in vivo testing. Some endogenous and processing factors affecting performance are also highlighted. In addition, innovations such as the coadministration of interleukin-4, and impregnation of the scaffold with platelet-rich plasma are introduced to increase scaffold performance. A brief overview of skeletal properties and metabolism, fracture healing, and essential features of bone grafts is provided to appreciate these innovations.

Materials with specific properties and structures are required for 3D nanofibers scaffold to perform well during tissue regeneration and drug delivery applications. When designing and fabricating 3D scaffolds, it is crucial to consider how the biomaterials interact with the native tissue structures and how they function in the surrounding environment. This chapter provided a brief discussion on the fabrication methods used to construct 3D biodegradable polymeric nanofibers scaffolds through electrospinning from 2D structures. Further, it extended to the characterisation required for the scaffold to be used in either tissue engineering or drug delivery. Additionally, this chapter presented recent progress in the practical application of 3D scaffolds that incorporate different therapeutic agents.

The intervertebral disc is a complex hierarchical structure, functiondependent, with the main function to provide support during movements, thus functioning as the shock absorber of the vertebral column. Its properties change from the outer toward the inner part, following the diverse composition. It is avascular with poor self-healing capability. During the degeneration process, the cascade of events causes the rupture of the structure and of the extracellular matrix, not able anymore to sustain load stress, leading to cervical or low back chronic pain. Current clinical treatments aim at pain relief but according to the severity of the disease, it might require spinal fusion or a total disc replacement made of metal or plastic disc substitutes, thus reducing the patient’s mobility. Tissue engineering and naturally derived hydrogels are gaining interest as important tools for mimicking and delivering cells or molecules either to regenerate a damaged part of the disc, but also its whole structure. Although in the last due decades several improvements have been achieved , the fabrication of IVD constructs, reproducing its structure and functions, is still challenging. For example the standardization of cell cultures conditions,cell sources, mechanical tests paramters, are fundamental achievements to translate the biofabricated products to the clinic.

Rapid prototyping (RP) is an advanced technique of fabricating a physical model, or complex assembly where computer-aided design (CAD) plays a significant role. The RP technique offers numerous advantages including providing information such as how a product will look like and/or perform, and in the first stage of the design and manufacturing cycle, allowing switches and improvements to be implemented earlier in the system. It acts quickly and reduces the risk of later/final stage costly errors. RP is considered to be an automated and cost-effective technique as it does not require special tools, involves minimal intervention of the operator, and minimizes material wastage. Different types of RP techniques are now commercially available and serving accordingly in many fields. By using rapid prototyping, engineers can produce and/or upgrade medical instruments that include surgical fasteners, scalpels, retractors, display systems, and so on. Tablets having a sustained drug release capability are also being manufactured by RP. Rehabilitation engineering also uses RP including the fabrication of biomedical implants and prostheses and craniofacial and maxillofacial surgeries. This chapter aims to provide an overview of rapid prototyping technology and various RP machines available commercially. This chapter also includes the applications of the RP technique in biomedical engineering focusing on the advanced scopes, capabilities, and challenges in the upcoming days.

Fabrication of off-the-shelf small diameter vascular graft as an alternative to current autologous graft in clinical setting i.e., internal mammary artery and saphenous veins has yet to be perfected. With cardiovascular diseases (CVD) topping the list of the causes of death worldwide, alternative vascular graft is especially crucial in patients with a lack of autologous grafts. Successful re-vascularisation could substantially lower the progression of CVD and mortality rate. This chapter delves into cells that are vital in developing a tissue engineered vascular graft (TEVG), ranging from the native tissue on the vascular bed to the potential cells that could be utilized, compounds that possibly could improve the available grafts and stents and future TEVG design.