Hai Lin

Androgenetic alopecia (AGA) is characterized by a compromised hair follicle microenvironment, where fibrosis driven extracellular matrix (ECM) stiffening and poor intrafollicular delivery synergistically obstruct stem cell regeneration. Here, we present a structurally engineered recombinant human type XVII collagen (rhCol XVII) developed to restore this niche through combined mechanomodulation and enhanced transfollicular delivery. By constraining its molecular weight to ~20 kDa while preserving critical amphiphilic helical domains, rhCol XVII achieves targeted penetration and accumulation within follicular structures. Once localized, rhCol XVII directly opposes dihydrotestosterone (DHT)-induced fibrotic remodeling by suppressing aberrant type I and III collagen deposition. This intervention reduces local ECM stiffness, relieving mechanical constraints on the hair follicle. Consequently, the alleviated mechanical stress triggers distinct changes in intracellular Ca²⁺ dynamics and cytoskeletal organization, driving Wnt/β-catenin pathway activation. Evaluated in a C57BL/6 mouse model of AGA, rhCol XVII accelerates hair regeneration and increases shaft diameter without detectable toxicity. This study establishes that reversing fibrosis-associated mechanical stiffening rehabilitates follicular regenerative capacity, positioning structure-guided biomaterials as a potent therapeutic strategy for AGA

Rotator cuff tears are highly prevalent among elderly individuals and athletes. They often lead to persistent pain and restricted mobility, and frequently necessitate surgical intervention. Despite advances in repair techniques, the reattachment of tendon to bone remains a major clinical challenge, with high failure rates primarily attributed to poor regeneration of the tendon‐to‐bone interface. In this study, we evaluated a collagen‐based porous scaffold to support tendon‐to‐bone healing after rotator cuff repair. First, analysis of public transcriptomic datasets from human lesional tendons identified a “failed healing” state characterized by disorganized fibrosis and activation of inflammatory pathways. Subsequently, MC3T3‐E1 and TTD6 cells were cultured on the scaffold to evaluate scaffold‐cell interactions. Transcriptomic analysis was performed to explore scaffold‐associated cellular responses, and the results suggested changes related to matrix interaction, cell adhesion, and repair‐associated remodeling. To evaluate the in vivo performance, a rotator cuff repair model in beagle dogs was established, and the scaffold was implanted at the injury site. Magnetic resonance imaging, biomechanical testing, and histological analyses showed improved tissue integration, mechanical performance, and histological organization. These findings suggest that the scaffold may support tendon‐to‐bone healing and has translational potential as a collagen‐based augmentation patch for rotator cuff repair.

Soft tissue defects resulting from trauma, congenital malformations, or aging pose significant clinical challenges. Autologous grafting is constrained by donor-site morbidity and unpredictable outcomes, while current injectable biomaterials fail to provide the combined benefits of mechanical support, biocompatibility, and bioactivity. Recombinant humanized collagen type III (rhCol III), produced through genetic recombination and biosynthesis, exhibits low immunogenicity, high hydrophilicity, and excellent cell-adhesive and immunomodulatory properties, demonstrating considerable potential for tissue repair and remodeling. Herein, a dual-crosslinked hydrogel composed of aldehyde-modified carboxymethyl cellulose methacrylate (CMC-MA-CHO) and rhCol III was developed for skin tissue regeneration. Structural analyses verified the successful functionalization with preserved methacrylate reactivity. The optimized 10% oxidized 2% formulation exhibited tissue-matched elasticity, excellent injectability, and efficient aldehyde–amine coupling efficiency. The resultant CMC-MA-CHO/rhCol III hydrogel featured interconnected porosity, enhanced thermal and enzymatic stability, and a prolonged rhCol III release exceeding 500 h. In vitro, the CMC-MA-CHO/rhCol III hydrogel enhanced Integrin/FAK/MAPK-mediated cell adhesion, promoted fibroblast migration, collagen expression without fibrotic differentiation, and polarized RAW264.7 macrophages towards a pro-regenerative M2 phenotype. Subcutaneous implantation in rats demonstrated superior biocompatibility, minimal capsule formation, and robust collagen remodeling with a physiological fibril architecture. Mechanistically, rhCol III-activated CMC-MA-CHO/rhCol III promoted tissue regeneration by upregulating PI3K/AKT signaling, potentially in coordination with TGFβ/Smad to maintain matrix homeostasis and reduce fibrosis. Collectively, this study presents a recombinant collagen–based injectable photocurable hydrogel possessing multifunctional regenerative potential, which provide a promising strategy for minimally invasive soft-tissue repair and aesthetic restoration.

Rapid wound healing of oral soft tissue may reduce the opportunity for infection and discomfort of patients. Given that recombinant humanized collagen type III (rhCol III) is considered a nonallergenic biomaterial and can help repair skin wound healing and activate tissue remodeling, the potential effect of rhCol III on palate mucosal wound healing was preliminarily evaluated in vitro and in vivo in this study. A mouse model of an oral palate wound was established, and rhCol III solutions were injected periwound, resulting in a significant acceleration in wound healing compared to the control groups. Histological evaluation showed that rhCol III promoted angiogenesis, collagen deposition, and cell proliferation. Furthermore, the results demonstrated that rhCol III could promote human gingival fibroblast (HGF) and human oral keratinocyte (HOK) proliferation, adhesion, and migration. To further explore the mechanism, RNA-sequencing analysis results showed that rhCol III could regulate the focal adhesion signaling pathway of HGFs. The expression of vinculin and phosphorylation of FAK (Tyr397 and Tyr576) in HGFs was upregulated with rhCol III treatment. In addition, inhibition of FAK phosphorylation could inhibit HGF migration. These results suggested that rhCol III promoted HGF migration by upregulating the focal adhesion signaling pathway. These findings suggest that the topical application of rhCol III is a promising treatment for oral soft tissue wounds with the potential for future clinical use.

Hydroxyapatite (HAp), traditionally recognized for its efficacy in bone regeneration, has rarely been explored for skin regeneration applications. This investigation explored HAp microspheres with distinct physicochemical properties tailored away from conventional bone regeneration parameters, and the capacity promoting skin regeneration and mitigating the aging process were investigated when encapsulated in hyaluronate hydrogels. By benchmarking against well-established dermal fillers like PMMA and PLLA, it was revealed the specific attributes of HAp that were conducive to skin regeneration, providing initial insights into the underlying mechanism. HAp enhanced the fibroblast functionality by triggering minimal adaptive immune responses and enhancing the Calcium Signaling and Motor Protein Signaling pathways. This modulation supported the production of normal collagen fibers, essential for ECM maturation and skin structural integrity. The significant ECM regeneration and remodeling capabilities exhibited by the HAp-encapsulated hybrid hydrogels suggested promising application in facial rejuvenation procedures, potentially making a breakthrough in aesthetic and reconstructive surgery.

Schematic diagram of in situ formed polypeptide hydrogel synthesis and promotion of skin repair.

The purpose of this study was to investigate the influence of the advanced structure of collagen on the chondrogenic differentiation of BMSCs encapsulated in collagen hydrogels, with an emphasis on MMPs which might affect the cell-material interactions. Collagen and gelatin-based hydrogels with comparable physicochemical properties but mainly distinctive in molecular structure were prepared and further utilized to load BMSCs to study the chondrogenesis. The detection results of MMPs in hydrogels with and without TIMP at both gene and protein levels suggested that MMPs were involved in cell recognition, adhesion, migration, proliferation and further remodeling of cell microenvironment. The chondrogenic gene detection, histological observation and extracellular matrix analysis indicated that the BMSCs were well differentiated into chondrocytes and maintained the phenotypes in collagen hydrogels (C group) which preserved the native structures, comparing with those results acquired from gelatin hydrogels (G group). Finally, the expression of several integrin subunits was investigated to analyze the connection of these cell membrane surface proteins and microenvironment remodeled by MMPs in collagen and gelatin hydrogels. The conclusion was drawn that the advanced structure of collagen affected the chondrogenesis of BMSCs via the cell-material interactions, among which MMPs were one of the major factors crucial to form appropriate microenvironment to modulate the BMSCs fate. Graphical abstract