Advanced Functional Biomaterials for Stem Cell Delivery in Regenerative Engineering and Medicine

Abstract

Stem cell-based therapies can potentially regenerate many types of tissues and organs, thereby providing solutions to a variety of diseases and injuries. However, acute cell death, uncontrolled differentiation, and low functional engraftment yields remain critical obstacles for clinical translation. Advanced functional biomaterial scaffolds that can deliver stem cells to the targeted tissues/organs and promote stem cell survival, differentiation, and integration to host tissues may potentially transform the clinical outcome of stem cellbased regenerative therapies. In this review, the authors briefly summarize sources of stem cells for transplantation, present the current state of the art in biomaterial design for stem cell delivery, and provide critical analysis for existing materials. Applications to the cardiovascular, neural, and musculoskeletal systems are highlighted with recent nonclinical studies and clinical trials. The authors also discuss how advances in biomaterials research can contribute to regenerative medicine research and stem cell therapies. application in the clinical setting. These challenges include the manipulation of stem cell fate pre-and post-transplantation and protection of the cells during and after their delivery to the target site. [3] The microenvironment, also referred to as stem cell niche, plays key roles in stem cell fate determination. [4] In vivo, the interplay among complex microenvironmental cues precisely regulate stem cell function so they may undergo self-renewal to maintain the stem cell pool or to undergo differentiation to regenerate tissue. However, the majority of current stem cell transplant strategies in clinical trials use injections with a buffer fluid, which provides insufficient protection and manipulation of cell fate. [5] As a result, the vast majority of transplanted cells die during their delivery or within a short time thereafter. Engineering approaches, especially in the biomaterials field, offer strategies to address the challenges and current limitations of stem cell therapy. Innovative design of biomaterials enables delicate control of their biophysical and biochemical properties, which provides an artificial niche to regulate stem cell functions. Delivery of cells via engineered biomaterial carriers can promote cell survival by reducing the microenvironmental shock (shear stress, inflammation, etc.), improving cell retention by preventing cell leakage and enhancing regenerative responses from delivered cells by manipulating stem cell fate. [6] In this review, we summarize and provide perspective on stem cell sources and the state of the art in the design, fabrication, and application of advanced functional biomaterials for stem cell delivery. We discuss current stem cell phenotypes and the requirements in biomaterial design and fabrication for successful stem cell transplantation. We also highlight recent nonclinical and clinical studies of stem cell therapy in the cardiovascular, neural, and musculoskeletal systems. Lastly, we conclude with an outlo...

Intravital three-dimensional bioprinting

“…The conventional bioprinting approaches require direct access to printing sites and free XYZ spatial movements of the bioprinting head, precluding the internal modifications of pre-existing 3D structures, without affecting the integrity of the structures of interest. On the other hand, injectable materials used as delivery vehicles hold great promise to improve the therapeutic efficacy for functional recovery of diseased or injured tissues and organs, including stem cell-based therapies 13 . An injectable hydrogel is the preferred material form for stem cell transplantation due to its potential to mimic the native stem cell microenvironment [14][15][16] .…”

PEG/HA Hybrid Hydrogels for Biologically and Mechanically Tailorable Bone Marrow Organoids

“…Starting from a synthetic PEG-based material we engineered a hybrid hydrogel by incorporating HA, a non-sulfated linear GAG highly abundant in many tissues, including in the BM, and already used in the clinics for few applications. [32] Compared to previously described GAG-based hybrid hydrogels, [25,26,33] we present a simplistic method to tune the ratio of GAG present in the hydrogel while maintaining its stiffness. This approach overcomes limitations of earlier approaches that required synthesis of various hydrogel precursor batches with varying degrees of modification.…”

Biomimetic Hybrid Systems for Tissue Engineering

“…All these features demonstrated the great clinical potential of regenerative therapies based on the use of stem cells. Wang et al [ 146 ] have recently summarized the main sources of stem cells for transplantation, presented the current state of the art in biomaterial design for stem cell delivery, and provided critical analysis for existing functional biomaterial scaffolds. Applications to the cardiovascular, neural, and musculoskeletal systems have also been highlighted with recent nonclinical studies and clinical trials.…”