Kelly X Huang

All Publications

• Understanding and Advancing Wound Healing in the Era of Multi-Omic Technology. Bioengineering (Basel, Switzerland) Jing, S. L., Suh, E. J., Huang, K. X., Griffin, M. F., Wan, D. C., Longaker, M. T. 2025; 13 (1)

  Abstract

  Wound healing is a complex, multi-phase process requiring coordinated interactions among diverse cell types and molecular pathways to restore tissue integrity. Dysregulation can lead to chronic non-healing wounds or excessive scarring, posing major clinical and economic burdens. Single-omics interrogate individual molecular layers, such as the genome, transcriptome, proteome, metabolome, or epigenome, and have revealed key cellular players, but provide a limited view of dynamic wound repair. Single-cell technologies provide higher resolution to single-omic data by resolving cell-type and state-specific heterogeneity, enabling precise characterization of cellular populations. Multi-omics integrates multiple molecular layers at single-cell resolution, reconstructing regulatory networks, epigenetic landscapes, and cell-cell interactions underlying healing outcomes. Recent advances in single-cell and spatial multi-omics have revealed fibroblast subpopulations with distinct fibrotic or regenerative roles and immune-epithelial interactions critical for re-epithelialization. Integration with computational tools and artificial intelligence (AI) continues to reveal cellular interactions, predict healing outcomes, and guide development of personalized therapies. Despite technical and translational challenges, including data integration and cost, multi-omics are increasingly shaping the future of precision wound care. This review highlights how multi-omics is redefining understanding of wound biology and fibrosis and explores emerging applications such as smart biosensors and predictive models with potential to transform wound care.

  View details for DOI 10.3390/bioengineering13010051

  View details for PubMedID 41595988

  View details for PubMedCentralID PMC12837972

• Clinical Features and Mechanisms of Differential Wound Healing and Scarring Across Anatomical Sites. Advances in wound care Yao, H., Jing, S. L., Huang, K. X., Griffin, M. F., Longaker, M. T., Wan, D. C., Li, D. J. 2025

  Abstract

  Significance: Fibrosis is associated with high rates of morbidity and mortality and poses a heavy burden on the health care system. Different regions of the body heal at different rates with varying degrees of fibrosis, with regions such as the extremities and trunk being more prone to scarring than the face and mucosa. Therapies that leverage the unique mechanisms underlying these anatomical differences in wound healing may be effective in mitigating fibrosis and scarring. Recent Advances: Recent studies in mice have revealed fibroblast-intrinsic signaling pathways that contribute to scar formation in different areas of the body, such as engrailed-1-positive fibroblasts and paired-related homeobox-1-positive fibroblasts in dorsal, ventral, and dermal scars, respectively. Novel approaches that target specific molecular pathways within fibroblasts may pave the way for effective therapies in replicating features of scar-resistant skin and facilitating wound healing. Critical Issues: Clinical practice and animal studies have shown some body regions to be more susceptible to fibrosis than others. However, our understanding on cellular and molecular mechanisms that contribute to this phenomenon remains limited. Future Directions: Advances in antiscarring therapy will benefit from harnessing several aspects of wound healing in regions less prone to fibrosis, including reducing mechanical tension, controlling angiogenic response, and modulating fibroblast subtypes. [Figure: see text] [Figure: see text].

  View details for DOI 10.1177/21621918251387627

  View details for PubMedID 41218822

• Clinical Features and Mechanisms of Differential Wound Healing and Scarring Across Anatomical Sites Advances in Wound Care Yao, H., Jing, S., Huang, K., Griffin, M., Longaker, M., Wan, D., Li, D. 2025

  Abstract

  Significance: Fibrosis is associated with high rates of morbidity and mortality and poses a heavy burden on the health care system. Different regions of the body heal at different rates with varying degrees of fibrosis, with regions such as the extremities and trunk being more prone to scarring than the face and mucosa. Therapies that leverage the unique mechanisms underlying these anatomical differences in wound healing may be effective in mitigating fibrosis and scarring. Recent Advances: Recent studies in mice have revealed fibroblast-intrinsic signaling pathways that contribute to scar formation in different areas of the body, such as engrailed-1-positive fibroblasts and paired-related homeobox-1-positive fibroblasts in dorsal, ventral, and dermal scars, respectively. Novel approaches that target specific molecular pathways within fibroblasts may pave the way for effective therapies in replicating features of scar-resistant skin and facilitating wound healing. Critical Issues: Clinical practice and animal studies have shown some body regions to be more susceptible to fibrosis than others. However, our understanding on cellular and molecular mechanisms that contribute to this phenomenon remains limited. Future Directions: Advances in antiscarring therapy will benefit from harnessing several aspects of wound healing in regions less prone to fibrosis, including reducing mechanical tension, controlling angiogenic response, and modulating fibroblast subtypes. [Figure: see text] [Figure: see text].

  View details for DOI 10.1177/21621918251387627

• Surgical Strategies for Tumors of the Pancreas and Duodenum. Cancers Reveron-Thornton, R. F., Huang, K. X., Delitto, D., Longaker, M. T., Norton, J. A. 2025; 17 (18)

  Abstract

  The recommended surgery for pancreatic tumors is dependent on the diagnosis. For pancreatic adenocarcinoma, duodenal, and ampullary adenocarcinoma, a Whipple pancreaticoduodenectomy with lymph node dissection is recommended. For small < 2 cm or non-imageable gastrinomas, duodenal transillumination, duodenotomy, duodenal tumor excision and adjacent lymphadenectomy is recommended. For large > 3 cm gastrinomas, a Whipple pancreaticoduodenectomy with adjacent lymph node dissection is recommended. For small 1-2 cm insulinomas, intraoperative ultrasound with enucleation is recommended. If the patient with gastrinoma, insulinoma, or multiple nonfunctional NETs occurs in the setting of MEN-1, a subtotal pancreatectomy with or without splenectomy with enucleation of pancreatic head tumors is recommended, with adjacent lymph node dissection. The detail of each procedure is described with illustrations.

  View details for DOI 10.3390/cancers17183091

  View details for PubMedID 41008933

  View details for PubMedCentralID PMC12468946

• Prophylactic Decellularized Adipose Matrix Treatment Mitigates Development of Radiation-Induced Cutaneous Fibrosis. Annals of plastic surgery Berry, C. E., Brenac, C., Kendig, C., Le, T., Huang, K. X., Griffin, M., Kameni, L., Longaker, M. T., Nazerali, R. S., Wan, D. C. 2025; 94 (6): 688-694

  Abstract

  Radiation therapy is an effective and common cancer therapy, but it often results in the formation of radiation-induced fibrosis (RIF). RIF of the skin manifests as symptoms including erythema, ulceration, hypovascularity, and poor wound healing. Subdermal injection of decellularized adipose matrix (DAM) has been studied as a potential means of correcting volumetric deficiencies while imparting regenerative effects to the overlying skin in patients with cutaneous RIF.DAM was injected subdermally to the flank region of adult C57BL/6J mice and irradiation was then applied to this area. Irradiated mice were given 4 weeks after completion of the irradiation protocol to allow for development of chronic RIF. Magnetic resonance imaging studies were performed throughout the recovery interval to monitor volume retention of the product. Longitudinal laser Doppler studies were used to follow perfusion. After experimental completion, flank skin was harvested and underwent histological and biomechanical evaluation.Histological staining with hematoxylin and eosin, Masson's trichrome, and picrosirius red stains demonstrated that irradiated skin architecture more closely resembled normal skin across measures of dermal thickness, collagen density, and collagen organization when DAM was injected prophylactically. Magnetic resonance imaging revealed that DAM volume retention decreased over time. Laser Doppler demonstrated improved perfusion of irradiated skin with prior DAM injection. Finally, biomechanical testing demonstrated that prophylactic DAM administration resulted in reduced skin stiffness compared to irradiated skin without DAM.This study reveals the therapeutic potential of prophylactic DAM treatment to prevent formation of RIF in skin. Our findings demonstrate that injected DAM volume is largely retained following irradiation and results in overlying skin retaining histologic and biomechanical characteristics of normal nonirradiated skin.

  View details for DOI 10.1097/SAP.0000000000004359

  View details for PubMedID 40358965

• Biomaterial Cues for Regulation of Osteoclast Differentiation and Function in Bone Regeneration ADVANCED THERAPEUTICS Shariati, K., Bedar, M., Huang, K. X., Moghadam, S., Mirzaie, S., LaGuardia, J. S., Chen, W., Kang, Y., Ren, X., Lee, J. C. 2024

  View details for DOI 10.1002/adtp.202400296

  View details for Web of Science ID 001357286300001

• Correlating Material Properties to Osteoprotegerin Expression on Nanoparticulate Mineralized Collagen Glycosaminoglycan Scaffolds ADVANCED HEALTHCARE MATERIALS Chen, W., Bedar, M., Zhou, Q., Ren, X., Kang, Y., Huang, K. X., Rubino, G., Kolliopoulos, V., Moghadam, S., Cascavita, C. T., Taylor, J. M., Chevalier, J. M., Harley, B. A. C., Lee, J. C. 2024; 13 (26): e2401037

  Abstract

  Precision material design directed by cell biological processes represents a frontier in developing clinically translatable regenerative technologies. While understanding cell-material interactions on multipotent progenitor cells yields insights on target tissue differentiation, equally if not more important is the quantification of indirect multicellular interactions. In this work, the relationship of two material properties, phosphate content and stiffness, of a nanoparticulate mineralized collagen glycosaminoglycan scaffold (MC-GAG) in the expression of an endogenous anti-osteoclastogenic secreted protein, osteoprotegerin (OPG) by primary human mesenchymal stem cells (hMSCs) is evaluated. The phosphate content of MC-GAG requires the type III sodium phosphate symporter PiT-1/SLC20A1 for OPG expression, correlating with β-catenin downregulation, but is independent of the effects of phosphate ion on osteogenic differentiation. Using three stiffness MC-GAG variants that do not differ significantly by osteogenic differentiation, it is observed that the softest material elicited ≈1.6-2 times higher OPG expression than the stiffer materials. Knockdown of the mechanosensitive signaling axis of YAP, TAZ, β-catenin and combinations thereof in hMSCs on MC-GAG demonstrates that β-catenin downregulation increases OPG expression by 1.5-fold. Taken together, these data constitute a roadmap for material properties that can used to suppress osteoclast activation via osteoprotegerin expression separately from the anabolic processes of osteogenesis.

  View details for DOI 10.1002/adhm.202401037

  View details for Web of Science ID 001253840000001

  View details for PubMedID 38885525

  View details for PubMedCentralID PMC11489015

• Bone-Anchored Maxillary Protraction for Adolescents with Cleft Palate and Class III Malocclusion: A Case Series CLEFT PALATE CRANIOFACIAL JOURNAL Chin, M. G., Gishen, K. E., Bedar, M., Huang, K. X., Laguardia, J. S., Moghadam, S., Lee, J. C., Panchura, J., Wilson, L. F. 2025; 62 (1): 13-20

  Abstract

  To describe the long-term treatment course of bone-anchored maxillary protraction (BAMP) and evaluate orthognathic surgical indications after BAMP. Retrospective case series. Craniofacial/Cleft Palate Program at the Orthopaedic Institute for Children in Los Angeles, CA. Twelve male patients with cleft palate (CP), unilateral cleft lip and palate (UCLP), or bilateral cleft lip and palate (BCLP) and Class III malocclusion treated with BAMP (mean age: 11.4 ± 2.6 years) were included. BAMP treatment was performed by placement of bone-anchored maxillary and mandibular plates connected with intraoral Class III dental elastics or maxillary plates connected to a facemask. We retrospectively assessed BAMP treatment variables, including age at surgery, revision surgeries, and treatment duration. The primary goal was correction to class I occlusion. Twelve patients underwent BAMP treatment for an average of 4.4 ± 2.4 years. Two patients were corrected to class I occlusion at the time of this report. Le Fort I advancement was no longer required in two patients (16.7%), it was required for nine patients (75.0%) and was completed for one patient following BAMP treatment (8.3%). This preliminary report demonstrated that BAMP treatment may be associated with a minimal reduction in the requirement for Le Fort I advancement at skeletal maturity. Future studies with larger sample sizes are necessary to confirm this association.

  View details for DOI 10.1177/10556656231219439

  View details for Web of Science ID 001125845400001

  View details for PubMedID 38086751