Advancements and Challenges in Hydrogel Engineering for Regenerative Medicine

Abstract

This manuscript covers the latest advancements and persisting challenges in the domain of tissue engineering, with a focus on the development and engineering of hydrogel scaffolds. It highlights the critical role of these scaffolds in emulating the native tissue environment, thereby providing a supportive matrix for cell growth, tissue integration, and reducing adverse reactions. Despite significant progress, this manuscript emphasizes the ongoing struggle to achieve an optimal balance between biocompatibility, biodegradability, and mechanical stability, crucial for clinical success. It also explores the integration of cutting-edge technologies like 3D bioprinting and biofabrication in constructing complex tissue structures, alongside innovative materials and techniques aimed at enhancing tissue growth and functionality. Through a detailed examination of these efforts, the manuscript sheds light on the potential of hydrogels in advancing regenerative medicine and the necessity for multidisciplinary collaboration to navigate the challenges ahead.

Keywords: biofabrication; hydrogel technology; regenerative medicine; stem cell differentiation; tissue engineering.

Figure 1

Schematic representation of developing effervescent porous hydrogels (EPHs) for tissue engineering applications [24].

Figure 2

Fabrication of the COL-HA hydrogel. (a) MSCs are resuspended in the collagen–HA hydrogel. (b) The cell–hydrogel mix can be applied using a pipette or syringe. (c) The hydrogel can be polymerized on demand with a short UVA light pulse and maintains its shape in the crosslinked state. (d) Crosslinking of the biopolymer network through the radical mediated thiol–ene addition of thiolated HA to collagen methacrylamide [68].

Figure 3

A schematic representation of chondrocyte-laden silk–GMA hydrogel transplantation and endoscopic observation of rabbit trachea for 6 weeks after transplantation. (A) The DLP-printed artificial trachea (10 × 10 × 2 mm, W × D × H) with chondrocytes from rabbit ears, cultured for 1 week. (B) (a,b) Removal of part of the trachea (10 × 10 mm). (c) Artificial trachea implantation. Scale bars represent 5 mm. (C) Endoscopy of trachea after transplantation at 2, 4, and 6 weeks. The transplanted chondrocyte-laden silk–GMA hydrogel showed that the internal diameter gradually increased after transplantation and the surrounding tissues grew into the surgical part of the trachea at 6 weeks after transplantation [10].

Figure 4

Scheme representing the tissue-engineered approach to enhance allograft healing. mMSCs were added to poly(ethylene glycol) macromer solutions (A) and custom molds were used to form hydrogel–cell constructs around decellularized allografts (e.g., tissue-engineered periosteum) (B). Encapsulated cells remained > 95% viable, as illustrated by the live/dead image (of GFP⁻ mMSCs; calcein AM (green = live cells) and ethidium homodimer (red = dead cells)) 24 h after encapsulation (C) [71].

Figure 5

Comparison of bone regeneration between Tetra and Oligo gels loaded with and without rhBMP-2 in a 3 mm diameter mouse calvarial critical defect model over a 42-day period. (a) In vivo micro-CT representative images of defects at 1, 14, 28, and 42 days post operation. (b) Visualization of bone density of the defect site and surrounding area at 42 days post operation. The same trimming dimension and approximate imaging location is used across all samples. Scale bar: 3 mm. (c) Quantitative measurement of bone mineral content (mg) and bone volume (mm³) of the defect site and surrounding cortical bone regions at 42 days, as represented in (b). Data presented as mean ± SD, n = 3 or 4. Statistical analysis performed using two-way ANOVA and Tukey’s multiple comparison test. p-value * < 0.05, *** < 0.001, ns—not significant [35].

Figure 6

Innovations and applications of hydrogel-based materials in regenerative medicine and related fields.