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Current treatments for alopecia with autograft hair transplantation face limitations that may preclude complete hair restoration and leave patients with donor site scars. Scaffold assisted artificial hair implantation as demonstrated in a rat model may provide an adjunct for hair restoration without donor site morbidity.To design and create porous high-density polyethylene (PHDPE) and expanded polytetrafluoroethylene (ePTFE) hair-bearing scaffolds and evaluate their biocompatibility in a rat model.For this single-institution randomized prospective animal study, 34 Sprague Dawley rats were randomly selected into 2 groups: 24 rats for direct implantation and 10 rats for delayed implantation. The direct-implantation group was randomly divided into 3 subgroups of 8 rats, which were observed for 2, 12, and 24 week.Each rat dorsum was implanted with 4 scaffolds—PHDPE and ePTFE with and without hair—in a randomized 4-quadrant manner. The rats in the direct-implantation group were observed to their selected time points of 2, 12, and 24 weeks. The rats in the delayed-implantation group were observed for 4 weeks at which, all well-healed scaffolds without hair were then percutaneously implanted with 2 follicular units of hair. These rats were then observed for another 4 weeks.During the clinical observation period, scaffolds were observed for signs of infection, extrusion, and persistence of follicular units. Following sacrifice, sagittal sections of scaffold and surrounding skin were fixed in formalin, stained with hematoxylin-eosin, and evaluated for degree of fibrovascular invasion and acute and chronic inflammation.Overall 94.5% (86 of 91) of the scaffolds were well healed at time of evaluation (2 week, 100% [32 of 32]; 12 week, 96.3% [26 of 27]; 24 week, 87.5% [28 of 32]); while 85.6% of artificial hair follicular units were intact at time of evaluation (2 week, 93.8% [30 of 32]; 12 week, 86.7% [26 of 30]; 24 week, 75.0% [21 of 28]). Within the delayed implant group 100% (19 of 19) of the hair-implanted scaffolds were well healed at 8 weeks, with 94.7% (36 of 38) of the follicular units intact; 100% of the delayed–hair implant scaffolds were well healed with 86.1% (36 of 38) of the follicular units intact. Kaplan-Meier log-rank analysis showed no significant difference in survival between ePTFE and PHDPE scaffolds, as well as scaffolds with hair and scaffolds without hair. Upon histological analysis, overall scaffolds with hair were noted to have greater chronic inflammation (95% CI, −0.81 to −1.10; P = .01), and PHDPE was noted to have significantly great fibrovascular integration (95% CI, −11.42 to −1.96; P = .01) compared with ePTFE.Overall, PHDPE and ePTFE hair bearing scaffolds were well tolerated in a rat model. Progressive loss of artificial hair may be percutaneously implanted without significant increases in infection or extrusion.NA.