Polymer-based microparticles in tissue engineering and regenerative medicine

Different types of biomaterials, processed into different shapes, have been proposed as temporary support for cells in tissue engineering (TE) strategies. The manufacturing methods used in the production of particles in drug delivery strategies have been adapted for the development of microparticles in the fields of TE and regenerative medicine (RM). Microparticles have been applied as building blocks and matrices for the delivery of soluble factors, aiming for the construction of TE scaffolds, either by fusion giving rise to porous scaffolds or as injectable systems for in situ scaffold formation, avoiding complicated surgery procedures. More recently, organ printing strategies have been developed by the fusion of hydrogel particles with encapsulated cells, aiming the production of organs in in vitro conditions. Mesoscale self-assembly of hydrogel microblocks and the use of leachable particles in three-dimensional (3D) layer-by-layer (LbL) techniques have been suggested as well in recent works. Along with innovative applications, new perspectives are open for the use of these versatile structures, and different directions can still be followed to use all the potential that such systems can bring. This review focuses on polymeric microparticle processing techniques and overviews several examples and general concepts related to the use of these systems in TE and RE applications. The use of materials in the development of microparticles from research to clinical applications is also discussed

Design and assessment of biodegradable macroporous cryogels as advanced tissue engineering and drug carrying materials

Cryogels obtained by the cryotropic gelation process are macroporous hydrogels with a well-developed system of interconnected pores and shape memory. There have been significant recent advancements in our understanding of the cryotropic gelation process, and in the relationship between components, their structure and the application of the cryogels obtained. As cryogels are one of the most promising hydrogel-based biomaterials, and this field has been advancing rapidly, this review focuses on the design of biodegradable cryogels as advanced biomaterials for drug delivery and tissue engineering. The selection of a biodegradable polymer is key to the development of modern biomaterials that mimic the biological environment and the properties of artificial tissue, and are at the same time capable of being safely degraded/metabolized without any side effects. The range of biodegradable polymers utilized for cryogel formation is overviewed, including biopolymers, synthetic polymers, polymer blends, and composites. The paper discusses a cryotropic gelation method as a tool for synthesis of hydrogel materials with large, interconnected pores and mechanical, physical, chemical and biological properties, adapted for targeted biomedical applications. The effect of the composition, cross-linker, freezing conditions, and the nature of the polymer on the morphology, mechanical properties and biodegradation of cryogels is discussed. The biodegradation of cryogels and its dependence on their production and composition is overviewed. Selected representative biomedical applications demonstrate how cryogel-based materials have been used in drug delivery, tissue engineering, regenerative medicine, cancer research, and sensing

Mechanical evaluation of implanted calcium phosphate cement incorporated with PLGA microparticles

In this study, the mechanical properties of an implanted calcium phosphate (CaP) cement incorporated with 20wt% poly (DL-lactic-coglycolic acid) (PLGA) microparticles were investigated in a rat cranial defect. After 2, 4 and 8 weeks of implantation, implants were evaluated mechanically (push-out test) and morphologically (Scanning Electron Microscopy (SEM) and histology). The results of the push-out test showed that after 2 weeks the shear strength of the implants was 0.4470.44MPa (average7sd), which increased to 1.3471.05MPa at 4 weeks and finally resulted in 2.6072.78MPa at 8 weeks. SEM examination showed a fracture plane at the bone–cement interface at 2 weeks, while the 4- and 8-week specimens created a fracture plane into the CaP/PLGA composites, indicating an increased strength of the bone–cement interface. Histological evaluation revealed that the two weeks implantation period resulted in minimal bone ingrowth, while at 4 weeks of implantation the peripheral PLGA microparticles were degraded and replaced by deposition of newly formed bone. Finally, after 8 weeks of implantation the degradation of the PLGA microparticles was almost completed, which was observed by the bone ingrowth throughout the CaP/PLGA composites. On basis of our results, we conclude that the shear strength of the bone–cement interface increased over time due to bone ingrowth into the CaP/PLGA composites. Although the bone–cement contact could be optimized with an injectable CaP cement to enhance bone ingrowth, still the mechanical properties of the composites after 8 weeks of implantation are insufficient for load-bearing purpose

Injectable hydrogels : An emerging therapeutic strategy for cartilage regeneration

Funding Information: The authors acknowledge the funding support from the North Staffordshire Medical Institute (NSMI Research Awards 2021). Arjan Atwal gratefully thanks Faculty of Medicine and Health Sciences , Keele University , for funding his PhD studentship.Peer reviewedPublisher PD

Bioinspired materials and tissue engineering approaches applied to the regeneration of musculoskeletal tissues

The musculoskeletal tissues have a prime role in the biomechanical support and metabolic activities of the human body. As musculoskeletal tissues are highly prone to injuries, conditions afflicting these tissues have a great impact on the quality of life of patients worldwide. Tissue engineering approaches hold the promise to develop bioengineered substitutes aiming at the regeneration of failing and injured tissue and organs. To effectively address the tissue-specific structural and biochemical features of musculoskeletal tissues, different biomaterials and techniques have been employed envisioning biomimetic solutions. Herein, the unique composition, structure, and function of the musculoskeletal tissues, namely bone, cartilage, and tendon, as well as state-of-the-art technologies to develop bioinspired strategies for tissue regeneration will be overviewed. Finally, this chapter will also discuss the unmet challenges and future perspectives in the field.FCT Project MagTT PTDC/CTM-CTM/29930/2017 (POCI-01- 0145-FEDER-29930) for A.I.G postdoc grant, the FCT Project PTDC/NAN-MAT/30595/2017 (POCI-01-0145-FEDER-30595) for P.S.B. postdoc grant, and for the assistant researcher contract (RL1) of M.T.R from the project “Accelerating tissue engineering and personalized medicine discoveries by the integration of key enabling nanotechnologies, marine-derived biomaterials and stem cells” supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). Authors acknowledge the financial support from the European Union Framework Programme for Research and Innovation HORIZON 2020, under the TEAMING Grant agreement No. 739572—The Discoveries CTR and the European Research Council 2017-CoG MagTendon (No. 772817

Small Molecule Drug Release Form in Situ Forming Degradable Scaffolds Incorporating Hydrogels and Bioceramic Microparticles

The present invention relates to an injectable system combining a hydrogel, a bioceramic and a degradable matrix that provides for sustained drug delivery and structural support to recovering tissue, such as bone and the periodontium

Injectable system and scaffolds to promote endochondral mechanism for bone regeneration

Tese de doutoramento. Engenharia Biomédica. Faculdade de Engenharia. Universidade do Porto, Department of Basic Sciences and Craniofacial Biology. New York University College of Dentistry. 200

Biomaterial-based strategies for craniofacial tissue engineering

Damage to or loss of craniofacial tissues, often resulting from neoplasm, trauma, or congenital defects, can have devastating physical and psychosocial effects. The presence of many specialized tissue types integrated within a relatively small volume leads to difficulty in achieving complete functional and aesthetic repair. Tissue engineering offers a promising alternative to conventional therapies by potentially enabling the regeneration of normal native tissues. Initially, a stimulus responsive biomaterial designed for injectable cell delivery applications was investigated with the goal of providing a substrate for osteogenic differentiation of delivered cells. In order to enable faster clinical translation, later efforts focused on novel combinations of regulated materials. Most common approaches using cell delivery for bone tissue engineering involve the harvest and ex vivo expansion of progenitor cell populations over multiple weeks and cell passages. The effect of aging and passage on proliferation and differentiation were analyzed using murine mesenchymal stem cells as a model. These cells lose their ability to proliferate and differentiate with increases in donor age and passages during cell culture. Delivery of uncultured bone marrow mononuclear cells was then investigated, and it was determined that when delivered to porous scaffolds these cells, which can be harvested, isolated, and returned to the body within the setting of a single operation, significantly increased bone regeneration in vivo. Finally, because these techniques of scaffold implantation and cell delivery would likely fail if delivered to an exposed or infected wound, a method of space maintenance was investigated. Space maintainers made of poly(methyl methacrylate) and having tunable porosity and pore interconnectivity were evaluated within a clean/contaminated mandibular defect. Low porosity space maintainers were found to prevent soft tissue collapse or contracture into the bony defect and allowed surrounding soft tissues to penetrate the pores of the implant, enabling healing over 12 weeks. The tissue response and wound healing characteristics of these implant was favorable when compared to solid or high porosity implants. Although optimization and further investigation of these techniques is necessary, in combination these approaches demonstrate one possible and translatable approach towards craniofacial tissue regeneration

Calcium Orthophosphate Bioceramics

The present review is intended to point the readers’ attention to the important subject of calcium orthophosphate bioceramics. Calcium orthophosphates by one-selves appear to be of a special significance for the human beings because they represent the inorganic part of calcified tissues of mammals. Therefore, many types of calcium orthophosphate-based bioceramics possess remarkable biocompatibility and bioactivity. Materials scientists extensively use this property in attempts to construct artificial bone grafts those are either entirely made of or only surface-coated by calcium orthophosphate bioceramics. Namely, self-setting calcium orthophosphate cements are very helpful in filling voids in damaged bones, while metallic implants covered by a surface layer of calcium orthophosphate bioceramics are widely used for hip joint endoprostheses and tooth substitutes. Porous bioceramicscaffolds made of calcium orthophosphates are very promising tools for tissue engineering applications. In this paper, an overview on the current knowledge on calcium orthophosphate bioceramics has been provided