The regeneration of the musculoskeletal system has been widely investigated. There is now detailed knowledge about the organs composing this system. Research has also investigated the zones between individual tissues where physical, mechanical and biochemical properties transition. However, the understanding of the regeneration of musculoskeletal interfaces is still lacking behind. Numerous disorders and injuries can degrade or damage tissue interfaces. Their inability to regenerate can delay the repair and regeneration process of tissues, leading to graft instability, high morbidity and pain. Moreover, the knowledge of the mechanism of tissue interface development is not complete. This review presents an overview of the most recent approaches of the regeneration of musculoskeletal interfaces, describing the latest in vitro, preclinical and clinical studies.
Regenerative therapies aim to develop novel treatments to restore tissue function. Several strategies have been investigated including the use of biomedical implants as three-dimensional artificial matrices to fill the defect side, to replace damaged tissues or for drug delivery. Bioactive implants are used to provide growth environments for tissue formation for a variety of applications including nerve, lung, skin and orthopaedic tissues. Implants can either be biodegradable or non-degradable, should be nontoxic and biocompatible, and should not trigger an immunological response. Implants can be designed to provide suitable surface area-to-volume ratios, ranges of porosities, pore interconnectivities and adequate mechanical strengths. Due to their broad range of properties, numerous biomaterials have been used for implant manufacture. To enhance an implant’s bioactivity, materials can be functionalised in several ways, including surface modification using proteins, incorporation of bioactive drugs, growth factors and/or cells. These strategies have been employed to create local bioactive microenvironments to direct cellular responses and to promote tissue regeneration and controlled drug release. This chapter provides an overview of current bioactive biomedical implants, their fabrication and applications, as well as implant materials used in drug delivery and tissue regeneration. Additionally, cell- and drug-based bioactivity, manufacturing considerations and future trends will be discussed.
The transition areas between different tissues, known as tissue interfaces, have limited ability to regenerate after damage, which can lead to incomplete healing. Previous studies focussed on single interfaces, most commonly bone-tendon and bone-cartilage interfaces. Herein, we develop a 3D in vitro model to study the regeneration of the bone-tendon-muscle interface. The 3D model was prepared from collagen and agarose, with different concentrations of hydroxyapatite to graduate the tissues from bones to muscles, resulting in a stiffness gradient. This graduated structure was fabricated using indirect 3D printing to provide biologically relevant surface topographies. MG-63, human dermal fibroblasts, and Sket.4U cells were found suitable cell models for bones, tendons, and muscles, respectively. The biphasic and triphasic hydrogels composing the 3D model were shown to be suitable for cell growth. Cells were co-cultured on the 3D model for over 21 days before assessing cell proliferation, metabolic activity, viability, cytotoxicity, tissue-specific markers, and matrix deposition to determine interface formations. The studies were conducted in a newly developed growth chamber that allowed cell communication while the cell culture media was compartmentalised. The 3D model promoted cell viability, tissue-specific marker expression, and new matrix deposition over 21 days, thereby showing promise for the development of new interfaces.
Substitution of ionic either anion or cation in a controlled amount into carbonated hydroxyapatite (CHA) structure is one of the efficient and safest ways in enhancing the properties of the materials. However, most of the works studied only focused on the physical and mechanical properties of single ionic substitution. For the first time, the influence of simultaneous ternary substitutions of divalent cations into porous CHA scaffolds on the physicochemical, mechanical, degradation and in vitro biological properties are investigated in the present study. Three different compositions of porous scaffolds with binary and ternary divalent cations, namely, pure CHA (S11), CoSr CHA (S21) and MgCoSr CHA (S31) were fabricated using polyurethane (PU) foam replication technique. Despite a small amount of Mg 2+ , Co 2+ and Sr 2+ added, these divalent cations had successfully substituted into the Ca 2+ site and remained as single phase B-type CHA. The produced scaffolds demonstrated open, interconnected and uniform pores. Interestingly, simultaneous ternary divalent cations substitution into CHA structure had successfully enhanced the compressive strength of the sintered scaffolds, also promoted better cell attachment and activities than the binary dopedand pure CHA scaffolds. It is important to note that the right choice of divalent cation can be the determining factor in tuning the physicochemical, mechanical and biological properties of CHA scaffolds.
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